Clinical Presentation - Acute Hemolytic Transfusion Reactions (immune)

Signs and symptoms usually appear within minutes after the transfusion is started but can occur anytime during the transfusion. They may include (but are not limited to):

• fever (temperature increase of more than 1oC)
• chills
• rigors
• nausea and vomiting
• anxiety
• malaise
• hypotension
• tachycardia
• burning along site of infusion
• skin flushing
• chest pain
• dyspnea, wheezing
• severe low back pain
• hemoglobinemia
• hemoglobinuria
• oliguria/anuria
• uncontrolled bleeding

 In the anesthetized patient, the only signs may be unexplained bleeding due to disseminated intravascular coagulation (DIC), falling blood pressure, and/or fever.

 The more severe transfusion reactions are characterized by shock, chills, fever, dyspnea, chest pain, back pain, headache and/or abnormal bleeding; these reactions may result in death. Hemoglobinemia, hemoglobinuria and subsequent hyperbilirubinemia are often detectable. Potentially life-threatening complications include:

• hypotension and shock
• disseminated intravascular coagulation
• renal failure

 Mechanisms

The mechanisms involved in AHTR are complex and not fully understood. Following transfusion of ABO-incompatible red cells, the recipient's ABO antibodies bind to antigens on the transfused red cells triggering complement activation. IgM and IgG anti-A, anti-B, and anti-A,B are all excellent complement binders. As the classical complement pathway progresses, anaphylatoxins C3a and C5a are released into the recipient's plasma. Once C9 is bound, the recipient's cells are destroyed by IVH. Cytokines, such as interleukin-1, tumor necrosis factor, interleukin-6, and interleukin-8, are believed to play key roles in the immune hemolysis and its serious sequelae.

In brief, activation of the complement cascade may lead to:

• intravascular hemolysis with hemoglobinemia and hemoglobinuria
• release of vasoactive complement components resulting in hypotension and shock
• thrombin and platelet activation culminating in DIC
• renal failure due to glomerular deposition of immune complexes, DIC, and reduced renal blood flow due to hypotension

Investigation of Acute Hemolytic Transfusion Reactions (immune)

IMPORTANT: When beginning an investigation, because similar symptoms may occur in several types of complications, all possibilities must be investigated. As patient history, clinical presentation and laboratory results accrue, a differential diagnosis is carefully assessed from which the ultimate diagnosis emerges.

Transfusion services should have clear policies describing the required investigation for transfusion complications. Below is an example of a protocol suitable for laboratory investigation of an adverse event such as an immediate/acute hemolytic transfusion reaction. Individuals should always adhere to the policies developed by their institutions.

• Immediate actions
• Laboratory investigation

Laboratory Investigation

Policies and procedures for investigating suspected hemolytic transfusion reactions will vary among transfusion services. As a minimum, the following should be done in accordance with laboratory policies and procedures:

• Check for clerical errors by:
  - reviewing patient identity on the compatibility label (tag)
  - Confirming that patient and donor have compatible blood types
  - Ensuring that the correct tag is attached to the correct blood product container
  - Retrieving the patient's pre-transfusion specimen and request form/worksheet and checking that the information on both is identical and that they match the compatibility tag
• Inspect the patient's post-transfusion specimen for visible hemolysis
• Perform a Direct Antiglobulin Test (DAT) on the patient's post-transfusion specimen
• Depending on results, investigate further and report as appropriate

Further Serological Investigation

Depending on the results of the initial investigation, the transfusion service will perform follow-up serologic testing according to its own policies and procedures. Some examples are outlined under further testing.

Treatment of Acute Hemolytic Transfusion Reactions (immune)

Treatment varies with the clinical condition of each patient and focuses on providing cardiovascular support with IV fluids and vasopressors.

Note, however, that care should be taken to avoid fluid overload in patients with impaired cardiac or renal function.

If present, disseminated Intravascular hemolysis (DIC) and hypotension must be treated early to limit renal damage.

If possible, further transfusions should not be given until the transfusion service has completed its serologic investigation and determined the cause of the reaction.

Reporting - Acute Immune Hemolytic Transfusion Reaction

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention of Acute Hemolytic Transfusion Reactions (Immune)

Prevention of acute intravascular hemolytic transfusion reactions is only possible:

• with careful, comprehensive identification of the patient at the bedside at the time of collection of the blood samples for pretransfusion testing and
• with careful comprehensive identification of the patient and the donor unit immediately prior to initiating the transfusion.
• Polices and procedures that prevent misidentification of the patient and/or donor unit must be in place in the hospital nursing manual and must be strictly adhered to.

Likewise policies and procedures that prevent misidentification of the patient's sample during blood grouping must be in place in the hospital transfusion service and must be strictly adhered to.

Acute Hemolytic Transfusion Reactions (immune) - Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Beauregard P, Blajchman MA. Hemolytic and pseudo-hemolytic transfusion reactions: an overview of the hemolytic transfusion reactions and the clinical conditions that mimic them. Transfus Med Rev 1994 Jul;8(3):184-99.  
2. Callum, JL, Kaplan, HS, Merkley, L L, Pinkerton, PH, Rabin Fastman, B, Romans, RA. Reporting of near-miss events for transfusion medicine: improving transfusion safety. Transfusion 2001; 41: 1204-11. [ Full text ] [ Medline ]
3. Capon SM, Goldfinger D. Acute hemolytic transfusion reaction, a paradigm of the systemic inflammatory response: new insights into pathophysiology and treatment. Transfusion 1995;35(6):513-20.
4. Davenport RD. Hemolytic transfusion reactions. In: Popovsky MA, ed. Transfusion reactions, 2nd ed. Bethesda, MD: AABB Press;2001. p.2-36.
5. Davenport RD. The role of cytokines in haemolytic transfusion reactions. Immunol Invest. 1995 Jan-Feb;24 (1-2): 319-31. [Medline]
6. Fitzpatrick T, Fitzpatrick L. Nursing management of transfusion reactions. In: Popovsky M, editor. Transfusion reactions, 2nd ed. Arlington, VA: AABB Press;2001. p.417-48.
7. Kaplan H. Lessons learned (editorial). Transfusion 2001;41(5): 575-6. [ Full text ]
8. Kleinman S, Chan P, Robillard P. Risks associated with transfusion of cellular blood components in Canada. Transfus Med Rev 2003; 17(2):120-162.
9. Larsson LG, Welsh VJ, Ladd DJ. Acute intravascular hemolysis secondary to out-of-group platelet transfusion. Transfusion 2000 Aug;40(8): 902 -6. [Full text ] [ Medline ]
10. Linden JV, Wagner K, Voytovich AE, Sheehan J. Transfusion errors in New York State: an analysis of 10 years' experience. Transfusion 2000;40(10):1207-13. [ Full text ] [ Medline ]
11. Park TS, Kim KU, Jeong WJ, Kim HH, Chang CL, Chung JS, Cho GJ, Lee EY, Son HC. Acute haemolytic transfusion reactions due to multiple alloantibodies including anti-E, anti-c and anti Jkb. J Korean Med Sci. 2003 Dec; 18(6): 894-6. [Medline]
12. Robillard P, Nawef KL, Jochem K. The Quebec hemovigilance system: description and results from the first years. Transfus Apheresis Sci. 2004 Oct; 31(2): 111-22. [Medline]
13. Sazama K, JD, DeChristopher PJ,Dodd R, Harrison CR, Shulman IA, Cooper ES, et al. Practice parameter for the recognition, management, and prevention of adverse consequences of blood transfusion. Arch Pathol Lab Med 2000 ;124(1): 61–70.
14. Stroncek D, Procter JL, Johnson J. Drug-induced hemolysis: cefotetan-dependent haemolytic anemia mimic an acute intravascular immune transfusion reaction. Am J Hematol. 2000 May; 64(1): 67-70. [Medline]
15. Telen M.J. Principles and problems of transfusion in sickle cell disease. Semin Hematol. 2001;38:315-23. [ Medline ].
16. Whitsett, CF, Robichaux, MG. Assessment of blood administration procedures:problems identified by direct observationand administrative incident reporting. Transfusion 2001; 41: 581-6. [ Full text ] [ Medline ]
17. Williamson LM, Lowe S, Love EM, Cohen H, Soldan K, McClelland DB, et al. Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports. Br Med J 1999; 319:16-9.
18. Win N, Doughty H, Telfer P, Wild BJ, Pearson TC. Hyperhemolytic transfusion reaction in sickle cell disease. Transfusion 2001 Mar; 41(3)323-8. [ Full text ] [Medline]

Clinical Presentation - Acute Non-Immune Hemolytic Transfusion Reactions

Signs and symptoms usually appear during the transfusion or within 24 hours of transfusion. Transfusing hemolysed red cells may result in hemoglobinemia and hemoglobinuria but usually not the other symptoms associated with immune-mediated AHTR.

However, there are rare reports of life-threatening reactions with hypotension and renal failure occurring.

Mechanism

Transfusion of hemolysed red cells results in hemoglobinuria. Lysed red cells may also lead to release of vasoactive or thrombogenic substances.

Investigation - Acute Non-Immune Hemolytic Transfusion Reactions

For an acute non-immune HTR the investigation does not reveal serologic abnormalities or misidentification errors but rather, in most cases, a handling, storage, or transfusion error or malfunction that results in physical or chemical destruction of red cells.

Non-immune hemolytic transfusion reactions should be suspected in the presence of unexplained hemoglobinuria that is temporally related to red cell transfusion but not associated with other signs and symptoms of an acute hemolytic transfusion reaction.

Transfusion services should have clear policies describing the required investigations for transfusion complications.  An example of an immediate investigation shows steps that could be used to investigate any immediate transfusion reaction.

Treatment - Acute Non-Immune Hemolytic Transfusion Reactions

With non-immune hemolysis treatment may be unnecessary, but the patient must be monitored for significant hemolysis.

If hypotension or renal failure occurs, treatment is similar to that for acute immune-mediated hemolytic reactions. i.e., it varies with the clinical condition of each patient and focuses on treating and managing the serious sequelae of intravascular hemolysis with IV fluids, vasopressors, and diuretics.

If possible, further transfusions should not be given until the transfusion service has completed its serologic investigation and determined the cause of the reaction.

Reporting - Acute Non-Immune Hemolytic Transfusion Reactions

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Acute Non-Immune Hemolytic Transfusion Reactions

Non-immune hemolytic transfusion reactions are usually due to errors involving handling, storage, and administration of blood components.

The best prevention involves education of all staff involved in administration of blood components to correctly follow protocols for the handling, storage and administration of blood components.

Support personnel involved in prevention of this type of transfusion reaction include:

• Messengers transporting components from the hospital transfusion service to the patient location. An education program should be developed to ensure they are aware of the handling requirements for blood components in transit.
• Transportation personnel handling blood components between the donor centre and the hospital transfusion service.
• Ambulance personnel handling blood components that are transported with patients between facilities.

See these resources:

• Visual inspection and transportation
• Storage
• Administration, including
  - Equipment, blood warmers, and rapid infusion devices
  - IV solutions and medications
  - Infusion and monitoring

Acute Non-Immune Hemolytic Transfusion Reactions: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Beauregard P, Blajchman MA. Hemolytic and pseudo-hemolytic transfusion reactions: an overview of the hemolytic transfusion reactions and the clinical conditions that mimic them. Transfus Med Rev 1994 Jul;8(3):184-99.
2. Davenport RD. Hemolytic transfusion reactions. In: Popovsky MA, ed. Transfusion reactions, 2nd ed. Bethesda, MD: AABB Press; 2001. p.1-44.
3. Win N, Doughty H, Telfer P, Wild BJ, Pearson TC. Hyperhemolytic transfusion reaction in sickle cell disease. Transfusion 2001 Mar.; 41(3)323-8. [ Full text ] [ Medline ]
4. Telen MJ. Principles and problems of transfusion in sickle cell disease. Semin Hematol 2001; Oct.; 38(4): 315-23. [ Medline ]

Clinical Presentation - Febrile Non-Hemolytic Transfusion Reactions

Signs and symptoms of a Febrile Non-Hemolytic Transfusion Reaction (FNHTR) can appear during the transfusion or within four hours of its completion. They may include:

• fever (>/= 38 degrees C and a change of  >/= 1 degree C from pretransfusion value)
• chills
• sensation of cold or
• rigors
• headache
• nausea

Mechanisms

FNHTR Mediated by Antibodies

The proposed mechanism for FNHTR to RBC is an antigen-antibody reaction between recipient antibodies to antigens on donor leukocytes in which cytokines are released by donor leukocytes. The cytokines released include interleukin 1 b (IL-1 b), interleukin 6 (IL-6), and tumor necrosis factor (TNF).

Another theory is that the recipient-donor WBC antigen-antibody reaction may activate complement, thus stimulating the recipient's macrophages to produce and release cytokines.

FNHTR Mediated by Accumulation of Cytokines During Storage

According to one proposed mechanism for FNHTR associated with transfusion of platelets, cytokines (IL-1 b,, IL-6, TNF), and possibly other biological response mediators, accumulate in the plasma in which platelets are stored and, when infused, cause the symptoms typical of these reactions. However, prestorage leukoreduction has not entirely eliminated the reactions, as would be expected if leukocyte-derived cytokines were solely responsible.

Investigation - Febrile Non-Hemolytic Transfusion Reactions

Transfusion services should have clear policies indicating the investigations required for suspected FNHTR and whether or not transfusions can be restarted. Because of the risk of hemolytic reactions with RBC and bacterial contamination of platelets, (and particularly since the introduction of universal prestorage leukoreduction and the resulting decrease in the frequency of FNHTR), extreme caution should be used if restarting transfusion.
In all cases, restarting transfusion should be

• exceptional rather than routine
• only with specific MD orders
• accompanied by close patient surveillance for the remainder of transfusion

An example of an immediate investigation shows steps that could be used to investigate any immediate transfusion reaction.

Because fever may occur in immediate and delayed hemolytic transfusion reactions and transfusion of a bacterially contaminated blood component, these complications must be excluded.

Clinical judgement should also be exercised based on all of the patient's symptoms, clinical condition, and prior history of transfusion reactions. For further discussion, see "Controversies in Transfusion Medicine: Should a Febrile Transfusion Response occasion the return of the blood component to the blood bank?" (pro and con by Widmann and Oberman, respectively) in Further Reading.

Suspected FNHTR to RBC Components

Since FNHTRs are diagnosed by exclusion, some laboratories tentatively diagnose reactions to RBC components as FNHTR if the symptoms are limited to those typical of mild to moderately severe FNHTR (fever, chills, discomfort, etc.) and there is no serologic or clerical evidence of a hemolytic transfusion reaction.

In the presence of universal prestorage leukoreduction, others prefer that donor RBC implicated in suspected FNHTR be cultured to rule out bacterial sepsis.

Suspected FNHTR to Platelet Components

Some laboratories follow the above policy with the addition, in the presence of more severe symptoms, that the platelets are returned to the laboratory for Gram stain and culture.

Because platelet components are stored at room temperature for up to five days, they have a higher incidence of septic transfusion reactions.

Treatment - Febrile Non-Hemolytic Transfusion Reactions

Treatment of FNHTR consists of treating the symptom of fever with an antipyretic such as acetominophen.

Demerol (meperidine) in small doses has also been used to treat severe shivering (rigors) that may occur in FNHTR.

Another strategy used by some clinicians is to premedicate patients who have experienced two suspected FNHTR with acetaminophen and diphenhydramine, although its efficacy has not been well studied.

If possible, further transfusions should not be given until the transfusion service has completed its serologic investigation and determined the cause of the reaction.

Reporting - Febrile Non-Hemolytic Transfusion Reactions

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Febrile Non-Hemolytic Transfusion Reactions

Canadian Blood Services (CBS) has adopted universal prestorage leukoreduction, in which leukocytes are removed from RBC and platelet components as part of the preparation process prior to storage.

• Prestorage leukoreduction to a threshold of 5 X 106 per component can prevent most FNHTR associated with RBC and platelet component transfusions.

Another strategy is to pre-medicate patients who have experienced two suspected FNHTR with acetaminophen and diphenhydramine, although its efficacy has not been well-studied.

Because prestorage leukoreduction cannot prevent the accumulation of some biological response mediators in platelet components such as IL-8, C3a, and C4a, an additional approach to preventing FNHTR associated with platelet components may be to remove the plasma just prior to transfusion. Currently this strategy is not routinely used, although it has been shown to be effective in preventing severe reactions to platelets. (See Further Reading: Heddle et al., Transfusion 2002.) .

Febrile Non-Hemolytic Transfusion Reactions: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Couban S, Carruthers J, Andreou P, Klama LN, Barr R, Kelton JG, Heddle NM. Platelet transfusions in children: results of a randomized, prospective, crossover trial of plasma removal and a prospective audit of WBC reduction. Transfusion. 2002 Jun.;42(6):753-8. [ Full text ] [ Medline ]
2. Enright H, Davis K, Gernsheimer T, McCullough JJ, Woodson R, Slichter SJ. Factors influencing moderate to severe reactions to PLT transfusions: experience of the TRAP multicenter clinical trial. Transfusion. 2003 Nov; 43(11):1545-52. [Medline]
3. Kleinman S, Chan P, Robillard P. Risks associated with transfusion of cellular blood components in Canada. Transfus Med Rev 2003; 17(2):120-162.
4. Heddle NM, Blajchman MA, Meyer RM, Lipton JH, Walker IR, Sher GD, et al. A randomized controlled trial comparing the frequency of acute reactions to plasma-removed platelets and prestorage WBC-reduced platelets. Transfusion. 2002 May;42(5):556-66. [ Full text ] [ Medline ]
5. Heddle NM, Kelton JG. Febrile nonhemolytic transfusion reactions. In: Popovsky M, editor. Transfusion reactions, 2nd ed. Arlington, VA: AABB Press; 2001. p. 45-82.
6. Heddle NM, Klama L, Meyer R, Walker I, Boshkov L, Roberts R, et al. A randomized controlled trial comparing plasma removal with white cell reduction to prevent reactions to platelets. Transfusion 1999 Mar.;39(3):231-8. [ Medline ]
7. Heddle NM. Pathophysiology of febrile nonhemolytic transfusion reactions. Curr Opin Hematol 1999 Nov.;6(6):420-6. [ Medline ]
8. Kelley DL, Mangini J, Lopez-Plaza I, Triulzi DJ. The utility of < or =3-day-old whole-blood platelets in reducing the incidence of febrile nonhemolytic transfusion reactions. Transfusion 2000 Apr.;40(4):439-42. [ Full text ] [ Medline ]
9. Oberman HA. Controversies in transfusion medicine: should a febrile transfusion response occasion the return of the blood component to the blood bank? Con. Transfusion 1994 Apr.;34(4):353-5.
10. Pruss A, Kalus U, Radtke H, Koscielny J, Baumann-Baretti B, Balzer D, Dorner T, Salama A, Kiesewetter H. Universal leukodepletion of blood components results in a significant reduction of febrile non-hemolytic but not allergic transfusion reactions. Transfus Apheresis Sci. 2004 Feb; 30(1): 41-6. [Medline]
11. Widmann FK. Controversies in transfusion medicine: should a febrile transfusion response occasion the return of the blood component to the blood bank? Pro. Transfusion 1994 Apr.;34(4):356-8.
12. Yazer MH, Podlosky L, Clarke G, Nahirniak SM. The effect of prestorage WBC reduction on the rates of febrile nonhemolytic transfusion reactions to platelet concentrates and RBC. Transfusion. 2004 Jan; 44(1):10-5. [Medline]

Clinical Presentation - Mild Allergic (Urticarial) Transfusion Reactions

Mild allergic reactions may occur anytime during the transfusion or shortly thereafter. The typical symptoms are local or generalized urticaria, pruritus, erythema (flushing), and wheezing.

Mechanism

IgE-mediated reactions are type I immediate hypersensitivity reactions. IgE has the ability to bind to mast cells and tissue basophils through Fc receptors on their cell membranes. Mast cells (armed with a surface coating of IgE) are triggered when the patient next becomes exposed to the antigen (allergen) recognized by the IgE. This leads to cross-linking of the bound IgE antibody, producing mast cell degranulation with release of preformed and new mediators of the allergic reaction.

Histamine is the most important preformed mediator. It causes vasodilation, increased vascular permeability, increased mucous secretion by nasal and bronchial glands, and smooth muscle contraction. Other granule compounds that mediate the reaction include heparin, enzymes, leukotrienes, cytokines, and activating factors such as the eosinophil and neutrophil chemotactic factors and platelet activating factor.

Investigation - Mild Allergic (Urticarial) Transfusion Reactions

Transfusion services should have clear policies as to what investigations are required for transfusion complications. An example immediate investigation shows steps that could be used to investigate any immediate transfusion reaction.

IMPORTANT: When beginning an investigation, because similar symptoms may occur in several types of complications, all possibilities must be investigated. As patient history, clinical presentation and laboratory results accrue, a differential diagnosis is carefully assessed from which the ultimate diagnosis emerges.

In the case of isolated urticaria and/or pruritis (i.e., no other signs or symptoms present) if the identification of the patient and donor do not reveal any discrepancies, a laboratory investigation is not usually indicated. The transfusion can usually be restarted after antihistamine is administered provided the patient is monitored and if in accord with an institution's policies and protocols.

Treatment - Mild Allergic (Urticarial) Transfusion Reactions

If the sole symptoms are hives and/or itching, the transfusion may be temporarily interrupted and the patient given an antihistamine, if directed by a physician.

When the reaction subsides, the transfusion may be continued at a slow rate of infusion. In patients known to experience such reactions, antihistamines may be prescribed prior to transfusion.

Reporting - Mild Allergic (Urticarial) Transfusion Reactions

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Mild Allergic (Urticarial) Transfusion Reactions

The physician treating a patient who has experienced repeated mild allergic reactions may prescribe antihistamines prophylactically.

Mild Allergic (Urticarial) Transfusion Reactions: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Couban S, Carruthers J, Andreou P, Klama LN, Barr R, Kelton JG, Heddle NM. Platelet transfusions in children: results of a randomized, prospective, crossover trial of plasma removal and a prospective audit of WBC reduction. Transfusion. 2002 Jun.; 42(6):753-8. [Full text ] [ Medline ]
2. Heddle NM, Blajchman MA, Meyer RM, Lipton JH, Walker IR, Sher GD, et al. A randomized controlled trial comparing the frequency of acute reactions to plasma-removed platelets and prestorage WBC-reduced platelets. Transfusion. 2002 May; 42(5): 556-66. [Full Text] [Medline]
3. Vamvakas EC, Pineda AA. Allergic and anaphylactic reactions. In: Popovsky M, editor. Transfusion reactions, 2nd ed. Arlington, VA: AABB Press; 2001. p. 83-128.

Clinical Presentation - Anaphylactic Transfusion Reactions

A severe allergic reaction may begin after infusion of only a few mL with symptoms that may be mild at first but can rapidly progress to loss of consciousness, shock, and, in rare cases, death. Reactions usually occur within 1 to 45 minutes of the start of transfusion, although the less severe anaphylactoid reactions may begin up to 2-3 hours after the transfusion was initiated.

Symptoms are categories by body system in the following table:

Mechanism

IgE-mediated reactions are type I immediate hypersensitivity reactions. IgE has the ability to bind to mast cells and tissue basophils through Fc receptors on their cell membranes. Mast cells (armed with a surface coating of IgE) are triggered when the patient next becomes exposed to the antigen (allergen) recognized by the IgE. This leads to cross-linking of the bound IgE antibody, producing mast cell degranulation with release of preformed and new mediators of the allergic reaction.

Histamine is the most important preformed mediator. It causes vasodilation, increased vascular permeability, increased mucous secretion by nasal and bronchial glands, and smooth muscle contraction. Other granule compounds that mediate the reaction include heparin, enzymes, leukotrienes, cytokines, and activating factors such as the eosinophil and neutrophil chemotactic factors and platelet activating factor.

In the case of class-specific antibodies to IgA, IgA deficiency has a frequency of about 1 in 700 in persons of European descent, defined as less than 0.0005 g/L of IgA. Some of these individuals will have immune or naturally occurring (no history of prior exposure to blood or blood products via pregnancy or transfusion) anti-IgA that is capable of causing anaphylactic reactions.

Investigation - Anaphylactic Transfusion Reactions

If a patient develops an anaphylactic or severe anaphylactoid transfusion reaction the patient’s pretransfusion serum must be screened for the presence of anti-IgA. Screening tests for IgA deficiency are available in many hospital laboratories. Anti-IgA usually occurs only in the presence of IgA deficiency. However it may also occur in the presence of a sub-class deficiency.

Patients without detectable IgA in screening tests (or if the test is unavailable), or patients who have experienced more than one anaphylactoid reaction should have specimens referred to Canadian Blood Services.

• If IgA antibodies are present, the patient is a candidate for IgA-deficient blood components
• If anti-IgA antibodies are absent, the patient should also be tested for haptoglobin deficiency, since anaphylactoid reactions due to this deficiency have also been described. Otherwise, no further laboratory testing is usually done.

It is important to differentiate anaphylactic/anaphylactoid transfusion reactions from other transfusion reactions such as immediate hemolytic transfusion reactions, circulatory overload, bacterial sepsis and TRALI, which may present similar signs and symptoms. It is also important to consider than an anaphylactic/anaphylactoid reaction may result from medical treatment other than blood transfusions.

Instructions for sending samples for IgA/anti-IgA testing:

1. Collect at least 2 mL of serum or plasma.
2. Forward sample and patient information to local CBS site.
3. Patient information includes:

• Full name
• Date of birth
• Sample collection date
• Originating lab contact information
• Identification number
• Pertinent transfusion history
• Reason for request

Treatment - Anaphylactic Transfusion Reactions

The transfusion must be immediately stopped and under no circumstances should it be restarted. The attending physician must be notified STAT.

The reaction is managed in the same way as a severe allergic reaction to other allergens (fluids, epinephrine, antihistimines, bronchodilators, vasopressors as appropriate).

Patients experiencing these symptoms should be closely monitored for at least six hours after onset of symptoms.

If possible, further transfusions should not be given until the transfusion service has completed its serologic investigation and determined the cause of the reaction.

Reporting - Anaphylactic Transfusion Reactions

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Anaphylactic Transfusion Reactions

Strategies for preventing anaphylactic/anaphylactoid transfusion reactions can be considered in three categories:

1. No IgA deficiency and no detectable anti-IgA

If the patient is not IgA deficient and no anti-IgA has been detected, and has experienced only a single anaphylactic or anaphylactoid reaction, a trial transfusion of unwashed blood components may be performed. The transfusion should be given under controlled clinical conditions, and close medical supervision as described below:

• obtain informed consent from the patient
• transfuse RBC, platelets, or plasma as indicated from unselected donors
• transfuse under close medical supervision (direct nursing supervision and physician immediately available)
• premedicate to reduce the severity, with emergency therapy readily available
• resume transfusion of standard blood components if no anaphylactic and anaphylactoid transfusion reaction occurs
• if anaphylactic or apaphylactoid reaction occurs, transfuse with washed blood components

2. Detectable anti-IgA (or anti-IgA levels pending)

For patients with anti-IgA or anti-IgA levels pending, transfuse with IgA deficient blood components. (See following table)

 3. IgA deficiency without detectable anti-IgA

Patients with IgA deficiency but without detectable anti-IgA who have experienced an anaphylactic or anaphylactoid transfusion reaction, should be treated as in (2) above. However it is possible that their transfusion reaction was unrelated to the IgA deficiency. For patients with IgA deficiency but without detectable anti-IgA who have never experienced an anaphylactic or anaphylactoid transfusion reaction, periodic repeat testing for anti-IgA may be considered before commencing subsequent elective transfusion. However, it is not necessary to routinely administer IgA deficient products to these patients.

Anaphylactic Transfusion Reactions: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Kleinman S, Chan P, Robillard P. Risks associated with transfusion of cellular blood components in Canada. Transfus Med Rev 2003 Apr.17(2):120-62.
2. Koda Y, Watanabe Y, Soejima M, et al. Simple PCR detection of haptoglobin gene deletion in anhaptoglobulinemic patient with antihaptoglobin antibody that causes anaphylactic transfusion reactions. Blood 2000; 95(4): 1138-43 [ Medline ] [ Full Text ]
3. Koskinen S, Tolo H, Hirvonen M, Koistinen J. Long-term follow-up of anti-IgA antibodies in healthy IgA-deficient adults. J Clin Immunol 1995 Jul, 15(4):194-8. [ Medline ]
4. Nishiki S, Hino M, Kumura T, Hashimoto S, Ohta K, Yamane T, Takubo T, Tatsumi N, Kitagawa S, Kamitani T, Watanabe Y, Shimda E, Juji T, Iida S. Effectiveness of washed platelet concentrate and red cell transfusions for a patient with anhaptoglobinemia with antihaptoglobin antibody. Transfus Med. 2002 Feb; 12(1): 71-3. [Medline]
5. Salama A, Temmesfeld B, Hippenstiel S, Kalus U, Suttorp N, Kiesewetter H. A new strategy for the prevention of IgA anaphylactic transfusion reactions. Transfusion. 2004 Apr; 44(4): 509-11. [Medline]
6. Sandler SG, Eckrich R, Malamut D, Mallory D. Hemagglutination assays for the diagnosis and prevention of IgA anaphylactic transfusion reactions. Blood 1994 Sep. 15; 84(6):2031-5. [ Medline ]
7. Sandler SG, Mallory D, Malamut D, Eckrich R. IgA anaphylactic transfusion reactions-Review of reported cases. Transf Med Rev 1995; 9(1):1-8.
8. Vamvakas EC, Pineda AA. Allergic and anaphylactic reactions. In: Popovsky M, editor. Transfusion reactions, 2nd ed. Arlington, VA: AABB Press; 2001. p. 83-128.

Clinical Presentation - Bacterial Sepsis

Some symptoms are similar to immune-mediated immediate hemolytic transfusion reactions and transfusion-related acute lung injury (TRALI). Milder reactions may be indistinguishable from febrile non-hemolytic transfusion reactions. The degree of severity relates to many factors, including the virulence of the organism, bacterial load infused, and host factors such as coincidental antibiotic therapy and level of immunosuppression.

Symptoms generally appear during or immediately after transfusion and may include:

• fever
• rigors
• nausea
• vomiting
• diarrhea
• dyspnea
• tachycardia
• lumbar pain
• rise or drop in systolic pressure
• shock
• circulatory collapse
• oliguria
• uncontrolled bleeding due to Disseminated Intravascular Coagulation (DIC)

Mechanism

Bacterial endotoxins stimulate macrophages, which in turn secrete cytokines such as tumour necrosis factor (TNF- , interleukin-1, IL-6, IL-8, etc. Cytokine release causes the signs and symptoms and may lead to acute septic shock.

Investigation - Bacterial Sepsis

Transfusion services should have clear policies describing the required investigations for transfusion complications. An example of an immediate investigation shows steps that could be used to investigate any immediate transfusion reaction.

Bacterial sepsis needs to be differentiated from complications that share some similar symptoms such as immediate hemolytic transfusion reactions, TRALI, and febrile non-hemolytic transfusion reactions. The immediate management of the patient as well as recommendations for reporting the reaction and the management of future transfusions are different for each of these complications.

CSA Standard Z902-04, Blood and Blood Components pertaining to investigating bacterial sepsis should be followed. Patient survival depends on

• early recognition
• stopping the transfusion
• rapidly beginning appropriate treatment

Laboratory Investigation

• recipient
• implicated donor unit or units (bag, not segments)
• IV solutions (if applicable)

Treatment - Bacterial Sepsis

Transfusion-associated bacterial sepsis is treated like any septic shock.

Septic and toxic reactions may be life-threatening, and treatment must be aggressive. Treatment should be initiated immediately after the collection of recipient blood samples for culturing. Treatment should include:

• broad-spectrum antimicrobials
• vasopressors to maintain blood pressure and urinary flow
• intravenous fluid therapy to maintain fluid and electrolyte balance

Other severe sequelae such as Disseminated Intravascular Coagulation (DIC) require prompt attention.

If possible, further transfusions should not be given until the transfusion service has completed its serologic investigation and determined the cause of the reaction.

Reporting - Bacterial Sepsis

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Bacterial Sepsis

Strategies for preventing bacterial sepsis vary according to potential cause. They are described in further detail below and include:

• Blood Donor Screening
• Blood Collection
• Component Storage and Transportation
• Visual Inspection of components
• Thawing and Pooling Blood Components
• Further possibilities.
• See Further Reading for more details about existing and proposed strategies being investigated

Blood Donor Screening

Strategies include deferral of potential donors for the following conditions:

• elevated temperature
• recent dental work
• not feeling well
• cold, flu, infection, or sore throat
• on antibiotics.

Blood Collection

Most bacteria found in platelets are normal skin flora, emphasizing the importance of aseptic blood collection techniques with careful skin sterilization.

Despite precautions, it may be almost impossible to decontaminate human skin. As well, needle coring may result in a small core of patient skin entering the needle at the time of blood collection and viable bacteria may be associated with deeper layers of skin, despite adequate surface disinfection. CBS has recently introduced whole blood collection bags with a sample diversion pouch for removal of an initial aliquot of 30-40 mL of donor blood. This approach reduces, but does not entirely eliminate, the rate of contamination by skin flora. However it does not decrease the rate of bacterial contamination due to other potentially more serious causes, in particular asymptomatic donor bacteremia.

Blood Component Storage and Transportation

Proper pretransfusion storage and transportation are critical to preventing bacterial growth in blood components that may be contaminated.

Policies must be in place to monitor and document the temperature of blood components, blood product storage equipment (e.g., refrigerators, freezers, platelet incubators), and transportation containers and take corrective action when necessary.

Visual Inspection

All blood components should be visually inspected upon labelling and entry into blood centre inventory, issue from the blood center, and prior to release for transfusion from the transfusion service. See an example of visual inspection criteria suitable for use in a transfusion service.

Individual hospital transfusion services may employ slightly different criteria as authorized by the medical director of the transfusion service.

Thawing & Pooling Blood Components

Several criteria relate to preventing bacterial contamination when transfusing, pooling, and thawing components. For example:

• When platelets are pooled immediately prior to transfusion, the product must be issued for transfusion within four hours.
• If RBC units are opened they must be transfused within 24 hours with appropriate storage in a controlled refrigerator until transfusion.
• Once transfusion is begun, a blood component should be transfused within four hours.
• Water baths used to thaw plasma and cryoprecipitate should be emptied and disinfected regularly. Donor units can be further protected from possible contamination by thawing components in plastic over-wraps.

NOTE: Frozen products must be thawed in the transfusion service according to standard operating procedures and specialized equipment and must NOT be thawed on hospital wards, unless the procedure is properly controlled and plasma thawing equipment is used.

Further Possibilities

Research on further ways to reduce transfusion-related transmission of bacteria and other organisms includes bacterial detection systems and pathogen inactivation.

Several methods for bacterial detection have been investigated, including visual inspection, culture, Gram's staining or acridine orange staining, PCR, chemiluminescence-linked rRNA hybridization, and urine reagent strips (to measure pH and glucose consumption). The American Association of Blood Banks (AABB) has recently published an Association Bulletin advising its membership on the use of those techniques. (See further reading)

Several pathogen inactivation methods are under investigation. These methods involve the exposure of blood components to reagents such as psoralen, riboflavin, dimethylmethylene blue and inactine in order to inactivate a variety of pathogens including viruses, bacteria, protozoa and fungi.

Bacterial Sepsis: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites. 

1. American Association of Blood Banks. Requirement for the implementation of bacterial detection methods. AABB Bulletin March 3, 2004.
2. America's Blood Centers. Bacterial contamination of blood components. (pdf file) Blood Bulletin Jul 2000;3(2).
3. Blajchman MA, Goldman M. Bacterial contamination of platelet concentrates: incidence, significance, and prevention. Semin Hematol 2001 Oct; 38(4 Suppl 11): 20-6. [ Medline ]
4. Blajchman MA, Goldman M, Baeza F. Improving the bacteriological safety of platelet transfusions. Transfus Med Rev. 2004 Jan;18(1):11-24. [ Full Text ] [ Medline ]
5. Brecher ME, Holland PV, Pineda AA, Tegtmeier GE, Yomtovian R. Growth of bacteria in inoculated platelets: implications for bacteria detection and the extension of platelet storage. Transfusion. 2000 Nov;40(11):1308-12. [ Full text ] [ Medline ]
6. CDC. Assessment of the frequency of blood component bacterial contamination associated transfusion reaction. (slide show outlining the BaCon Study Adverse Reaction in USA from 1997-2000) Also see recipient adverse reaction forms.
7. Chang AH, Kirsch CM, Mobashery N, Johnson N, Levitt LJ. Streptococcus bovis septic shock due to contaminated transfused platelets. Am J Hematol. 2004 Nov; 77(3): 282-6. [Medline]
8. Goldman M, Blajchman MA. Bacterial contamination. In: Popovsky MA, ed. Transfusion reactions, 2nd ed. Bethesda, MD: AABB Press;2001. p.129-54.
9. Golubic-Cepulic B, Budimir A, Plecko V, Plenkovic F, Mrsic M, Sarlija D, Vuk T, Skrlin J, Kalenic S, Labar B. Morganella morganii causing fatal sepsis in a platelet recipient and also isolated from a donor’s stool. Transfus Med. 2004 Jun; 14(3): 237-40. [Medline]
10. Hillyer CD, Josephson CD, Blajchman MA, Vostal JG, Epstein JS, Goodman JL. Bacterial contamination of blood components: risks, strategies, and regulation: Joint ASH and AABB Educational Session in Transfusion Medicine. Hematology (Am Soc Hematol Educ Program). 2003;:575-89. [ Medline ]
11. Jafari MJ, Forsberg J, Gilcher RO, Smith JW, Crutcher JM, McDermott M, Brown BR, George JN. Salmonella sepsis caused by a platelet transfusion from a donor with a pet snake. NEJM Oct 3, 2002: 14 Vol 347: 1075-1078.
12. Kim DM, Brecher ME, Bland LA, Estes TJ, Carmen RA, Nelson EJ. Visual identification of bacterially contaminated red cells. Transfusion 1992 Mar-Apr;32(3):221-5. [ Medline ]
13. Kopko PM, Holland PV. Mechanisms of severe transfusion reactions. Transfus Clin Biol 2001 Jun;8(3):278-81. [ Medline ]
14. Kuehnert MJ, Roth VR, Haley NR, Gregory KR, Elder KV, Schreiber GB, et al. Transfusion-transmitted bacterial infection in the United States, 1998 through 2000. Transfusion 2001 Dec; 41(12): 1493-9. [ Full text ] [ Medline ]
15. Lee, JH. Workshop on Bacterial Contamination of Platelets. CBER, FDA September 24, 1999.(June 1, 2000).
16. Reading FC, Brecher ME. Transfusion-related bacterial sepsis. Curr Opin Hematol. Nov. 2001;8(6)380-6. [ Medline ]
17. Roth VR, Kuehnert MJ, Haley NR, Gregory KR, Schreiber GB, Arduino MJ, et al. Evaluation of a reporting system for bacterial contamination of blood components in the United States. Transfusion 2001 Dec; 41(12): 1486-92. [ Full text ] [ Medline ]
18. Wagner SJ. Transfusion-transmitted bacterial infection: risks, sources and interventions. Vox Sang. 2004 Apr; 86(3): 157-63.

Clinical Presentation - Transfusion-Related Acute Lung Injury (TRALI)

By Tanya Petraszko, MD FRCPC and Heather Hume, MD FRCPC

Symptoms of TRALI typically develop during, or within 6 hours of a transfusion. Patients present with the rapid onset of dyspnea and tachypnea. There may be associated fever, cyanosis, and hypotension. Clinical exam reveals respiratory distress and pulmonary crackles may be present with no signs of congestive heart failure or volume overload. CXR shows evidence of bilateral pulmonary edema unassociated with heart failure (non-cardiogenic pulmonary edema), with bilateral patchy infiltrates, which may rapidly progress to complete "white out" indistinguishable from Acute Respiratory Distress Syndrome (ARDS).

Treatment and Clinical Course - Transfusion-Related Acute Lung Injury (TRALI)

By Tanya Petraszko, MD FRCPC and Heather Hume, MD FRCPC

Treatment of TRALI is supportive. Mild forms of TRALI may respond to supplemental oxygen therapy. Severe forms may require mechanical ventilation and ICU support. As with ARDS there is no role for diuretics or corticosteroids. The majority of patients recover within 72 to 96 hours and subsequently recover to their baseline pulmonary function without apparent sequelae. However, some patients are slower to recover and may remain hypoxic with persistent pulmonary infiltrates up to seven days. As stated above, approximately 5 to 10% of cases are fatal in spite of aggressive supportive care.

Differential Diagnosis

The differential diagnosis of acute lung injury after transfusion includes transfusion-associated circulatory overload (TACO), cardiogenic edema, allergic and anaphylactic transfusion reactions, and bacteremia/sepsis due to transfusion of bacterially contaminated blood products.

TRALI may be distinguished from TACO and cardiogenic pulmonary edema by the absence of signs of circulatory overload such as a normal central venous pressure (CVP) and normal pulmonary capillary wedge pressure (PCWP). Clinical response to diuretics also suggests a diagnosis of TACO rather than TRALI. Allergic and anaphylactic transfusion reactions may be manifest as hypotension and respiratory distress but are marked by laryngeal edema or bronchospasm with wheezing and a normal CXR. Transfusion transmitted bacteremia my present with fever, hypotension, and culminate in severe sepsis with associated acute lung injury which may be difficult to distinguish from TRALI. The presence of positive blood cultures is a useful delineating finding.

Pathophysiology

The hallmark of acute lung injury (ALI) is that of increased pulmonary microvascular permeability with increased protein in the edema fluid. This is true regardless of the cause of the ALI.

It is hypothesized that TRALI may be precipitated by the infusion of donor antibodies directed against recipient leukocytes. The infusion of donor anti-HLA (human leukocyte antigens) or anti-HNA (human neutrophil antigens) antibodies is thought to directly cause complement activation, resulting in the influx of neutrophils into the lung, followed by neutrophil activation and release of cytotoxic agents, with subsequent endothelial damage and capillary leak. Donor derived antibodies to HLA class I antigens and neutrophils have been demonstrated in up to 89% of TRALI cases examined in the literature.

An alternate hypothesis argues that TRALI is the result of at least two independent clinical events: the first is related to the clinical condition of the patient (infection, cytokine administration, recent surgery, or massive transfusion) that causes activation of the pulmonary endothelium. This then leads to the sequestration of primed neutrophils to the activated pulmonary endothelium. The second event is the infusion of donor derived anti-HLA or anti-HNA antibodies directed against antigens on the neutrophil surface and/or biological response modifiers (e.g., lipids) in the stored blood component that activate these adherent, functionally hyperactive neutrophils, causing neutrophil-mediated endothelial damage and capillary leak. Many studies in the literature support this hypothesis which may explain how some TRALI reactions occur in the absence of donor HLA/HNA antibodies, or why TRALI reactions do not occur in all recipients of blood components from donors who are known to have these antibodies.

Yet a third hypothesis suggests that high levels of donor derived vascular endothelial growth factor (VEGF) or antibodies to class II HLA antigens residing on pulmonary vascular endothelium may directly cause endothelial shape change and fenestration. This theory purports to explain the syndrome in neutropenic patients.

Identification and Definition - Transfusion-Related Acute Lung Injury (TRALI)

By Tanya Petraszko, MD FRCPC and Heather Hume, MD FRCPC

Identifying TRALI

It is imperative that medical personnel and hospitals identify suspected cases of TRALI and report them to Canadian Blood Services. The reporting of TRALI allows us to better understand the true incidence of this reaction, in addition to its clinical course and associated mortality. Further, by identifying cases of TRALI , CBS can take steps to prevent further cases of TRALI by removing companion components of units that may have caused the reaction and by investigating donors involved in these cases and deferring them from further donations if they are found to be implicated as outlined below.

Definition

Canadian Blood Services has adopted the definition put forth by the Canadian Consensus Conference Panel on TRALI as outlined below. This definition is applied consistently to all cases of TRALI reported to CBS and is used to determine whether reported cases will be investigated.

Because the diagnosis of Acute Lung Injury (ALI) can be difficult, it is important for the transfusion service medical director and the patient’s physician to communicate to determine, in particular, whether a patient has evidence of volume overload. Although ALI and hydrostatic pulmonary edema may coexist, the latter is a more common complication of transfusion and must be excluded in order for a diagnosis of TRALI or possible TRALI to be made.

Prevention - Transfusion-Related Acute Lung Injury (TRALI)

By Tanya Petraszko, MD FRCPC and Heather Hume, MD FRCPC

Hospitals

It is unlikely that TRALI can ever be entirely prevented, but its frequency may be reduced by the judicious use of blood components only for indications that are justified based on sound medical evidence. Hospitals should have procedures in place (e.g. blood utilization guidelines, blood conservation programs) which minimize unnecessary transfusions. In addition, hospital medical staff must continue to have a high index of suspicion in order to diagnose TRALI appropriately. All cases of TRALI or possible TRALI should be reported to Canadian Blood Services (in addition to the Provincial/Territorial Surveillance office as part of the TTISS program) who in turn is required to report all possible TRALI or possible TRALI cases to Health Canada.

Reporting

Cases of suspected TRALI should be reported to CBS using standard procedure for reporting Adverse Reactions. In order to correctly and consistently diagnose TRALI, the following information must be included in the report:

• Timing of transfusion with respect to symptom onset
• Presence of other risk factors for acute lung injury (see Table 3)
• CXR findings
• Evidence of hypoxia: PaO2 or SaO2
• Clinical indicators of volume status such as clinical evaluation, response to diuretics (if given), or where available JVP, PCWP, CVP, echocardiogram report etc.

In addition to the standard procedure for reporting adverse event, and in order to fully investigate and identify TRALI cases; patient samples must be sent for further testing. Complete the TRALI Patient Data form and forward the original as instructed to the local CBS site and photocopy of the form with samples to the named testing laboratory. TRALI Patient Data Form

Blood Supplier

Recognizing that donor derived antibodies may be one of the causes of TRALI, CBS has adopted a standardized, national donor management strategy in an attempt to improve the safety of the blood supply for Canadians by reducing the risk of TRALI.

Secondary Prevention

Secondary prevention refers to the management of donors whose donations have been temporally associated with a TRALI or possible TRALI reaction. In order to evaluate such donors and their continued eligibility to donate, the following definitions apply:

The disposition of donors associated with or implicated in a TRALI reaction is provided in the following table:

Table 5: Disposition of Donors Involved in a Reported TRALI
Donor	Test Results	Disposition
Implicated donor	Positive as per definition	Defer
Associated donor	Negative	Washed RBC Plasma for fractionation
	Positive for HLA antibodies but recipient crossmatch not available	Washed RBC Plasma for fractionation
	Positive for HNA antibodies	Defer

Note CBS is currently implementing more sensitive testing methods which will allow donors who test negative to be redefined as not-implicated. Donors who are not implicated following a TRALI investigation will be able to continue to donate without restriction.

Primary Prevention

Primary prevention refers to measures taken to reduce TRALI that are unassociated with a particular TRALI event. In the fall of 2007, the AABB published the recommendation that “...blood collecting facilities should implement interventions to minimize the preparation of high plasma-volume components from donors known to be leukocyte-alloimmunized (i.e. donors with antibodies to leukocytes) or who are at increased risk of leukocyte alloimmunization”.

In an effort to reduce the incidence of TRALI, Canadian Blood Services has implemented several measures to institute the use of predominantly male plasma for preparation of high-volume plasma components and to reduce the use of plasma from donors at high risk for HLA immunization, particularly previously pregnant females.

TRALI reduction measures began with the use of predominantly male plasma for production of Frozen Plasma, Fresh Frozen Plasma, cryosupernatant plasma and plasma for resuspension of platelet pools in October 2007.

In March 2008 these measures were expanded to include predominately male apheresis plasma donations.

On July 20, 2009 CBS began collecting apheresis platelets from males and females without a history of pregnancy.

The majority of plasma made from female whole blood donors is sent to the fractionator to be processed into plasma protein products such as intravenous immunoglobulin (IVIG) and albumin.

CBS no longer issues plasma or platelets made from female directed donors unless there is a clear medical indication for their use and after consultation and approval of the site Medical Director. Red cells may be issued from female directed donors as well as red cells, platelets and plasma, as required, from male directed donors.

Despite the move towards predominantly male plasma for transfusion, female plasma from female donors continues to be critically important to support the blood product needs of Canadian patients and may still be issued to meet group or component specific urgent shortfalls eg, Group group AB FFP, HLA or HPA matched platelets, IgA deficient donors.

The CBS TRALI Review Group

The TRALI Medical Review Group (TMRG) was established at Canadian Blood Services in 2006 as a national resource team to assist physicians at CBS in the management of reported TRALI cases. The TMRG is available to CBS physicians to review the results of TRALI investigations, to determine donor management in cases where the results are not straightforward, to assist CBS physicians in applying the definition of TRALI consistently and investigating/managing donors when the diagnosis is not immediately apparent. In addition, the TMRG is responsible for developing national policies with respect to the investigation of TRALI within CBS, for developing educational strategies for hospitals, community physicians and other health care providers and health authorities with respect to TRALI identification and reporting.

Members of the TMRG include Dr B. Hannach (Toronto), Dr T. Petraszko (Vancouver), Dr K. Webert (Hamilton), Dr Y Lin (Toronto), Dr C Saw (Winnipeg),  Dr M Goldman (Ottawa) , Dr. J. Hannon (Edmonton) and Dr. D. Towns (Calgary).

Further Reading - Transfusion-Related Acute Lung Injury (TRALI)

This is a comprehensive list of pertinent TRALI related articles where the reader may find further information.

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

Recent Reviews

1. Marik PE, Corwin, HL. Acute lung injury following blood transfusion: Expanding the definition. Crit Care Med 2008; 36 (11): 3080- 84.
2. Triulzi, DJ. Transfusion Related Acute lung injury: current concepts for the clinician. Anesthesia and analgesia. 2009;108 (3): 770-76
3. Chapman CE, Stainsby D, Jones H, Love E, Massey E, Win N, Navarrete C, Lucas G, Soni N, Morgan C, Choo L, Cohen H, Williamson LM. Ten years of hemovigilance reports of transfusion-related acute lung injury in the United Kingdom and the impact of preferential use of male donor plasma. Transfusion. 2008 Oct 28. [Epub ahead of print]
4. Silliman CC, McLaughlin NJ.Transfusion-related acute lung injury. Blood Reviews 2006; 20(3):139-59.
5. Silliman CC, Ambruso DR, Boshkov LK. Transfusion-related acute lung injury. Blood 2005; 105(6):2266-73.
6. Bux J.Transfusion-related acute lung injury (TRALI): a serious adverse event of blood transfusion. Vox Sanguinis 2005; 89(1):1-10.
7. Shander A, Popovsky MA. Understanding the consequences of transfusion-related acute lung injury. Chest.2005; 128(5 Suppl 2):598S-604S.

Definition/Consensus articles

1. Toy P, Popovsky MA, Abraham E, Ambruso DR, Holness LG, Kopko PM, McFarland JG, Nathens AB, Silliman CC, Stroncek D; National Heart, Lung and Blood Institute Working Group on TRALI. Crit Care Med. 2005;33(4):721-6.
2. Kleinman S, Caulfield T, Chan P, Davenport R, McFarland J, McPhedran S, Meade M, Morrison D, Pinsent T, Robillard P, Slinger P. Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel. Transfusion. 2004;44(12): 1774-89.
3. Skeate RC, Eastlund T. Distinguishing between transfusion related acute lung injury and transfusion associated circulatory overload. Current Opinion in Hematology. Nov 2007; 14(6):682-687.
4. Gajic O, Gropper MA, Hubmayr RD. Pulmonary edema after transfusion: How to differentiate transfusion-associated circulatory overload from transfusion-related acute lung injury. Crit Care Med. 2006;34(5) Suppl:S109-S113.

Pathogenesis

1. Jacobi KE, Wanke C, Jacobi A, Weisbach V, Hemmerling TM. Determination of Eicosaniod and cytokine production in salvaged blood, stored red blood cell concentrates, and whole blood. J Clin Anesth 12: 94-99, 2000.
2. Kopko PM, Paglieroni TG, Popovsky et al. TRALI: correlation of antigen-antibody and monocyte activation in donor-recipient pairs. Transfusion 2003;43:177-184.
3. Densmore, TL, Goodnough, LT, Ali S, Dynis M, Chaplin H. Prevalence of HLA sensitization in female apheresis donors. Transfusion 1999; 39:103-6.

Pathophysiology of TRALI

1. Silliman CC, Curtis BR, Kopko PM, et al. Donor antibodies to HNA-3a implicated in TRALI reactions prime neutrophils and cause PMN-mediated damage to human pulmonary microvascular endothelial cells in a two-event in vitro model. Blood. 2007;109(4): 1752-1755.
2. Curtis BR, McFarland JG. Mechanisms of transfusion-related acute lung injury (TRALI): anti-leukocyte antibodies. Critical Care Medicine. 2006; 34(5 Suppl):S118-23.
3. Silliman CC.The two-event model of transfusion-related acute lung injury. Critical Care Medicine. 2006; 34(5 Suppl):S124-31.
4. Toy P, Hollis-Perry KM, Jun J, Nakagawa M. Recipients of blood from a donor with multiple HLA antibodies: a lookback study of transfusion-related acute lung injury. Transfusion. 2004 Dec; 44(12): 1683-8.
5. Kopko PM. Leukocyte antibodies and biologically active mediators in the pathogenesis of transfusion-related acute lung injury. Curr Hematol Rep. 2004 Nov;3(6): 456-61.
6. Silliman CC, Bjornsen AJ, Wyman TH, Kelher M, Allard J, Bieber S, Voelkel NF. Plasma and lipids from stored platelets cause acute lung injury in an animal model. Transfusion. 2003 May; 43(5): 633-40.
7. Silliman CC, Boshkov LK, Mehdizadehkashi Z, Elzi DJ, Dickey WO, Podlosky L, Clarke G, Ambruso DR. Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. Blood. 2003; 101(2): 454-62

Prevention/Donor Management

1. Triulzi DJ, Kleinman S, Kakaiya RM et al. The effect of previous pregnancy and transfusion on HLA alloimmunization in blood donors: implications for a transfusion related acute lung injury risk reduction strategy. Transfusion 2009; 49(9):1825-35.
2. Engelfriet CP, REesink HW, Wendel S et al. Measures to prevent TRALI. Vox Sang 2007; 92 (3): 258-77.
3. AABB association bulletin #05-09
4. AABB association bulletin #06-07

For Nurses

1. Knippen MA. Transfusion-related acute lung injury. Am J Nursing. 2006;106(6):61-4.

Older Reviews

1. Kopko PM. Review: transfusion-related acute lung injury: pathophysiology, laboratory investigation, and donor management. Immunohematol. 2004; 20(2): 103-11.
2. Looney MR, Gropper MA, Matthay M. Transfusion-related acute lung injury: a review. Chest. 2004 Jul; 126(1): 249-58.
3. Webert KE, Blajchman MA. Transfusion-related acute lung injury. Transfus Med Rev. 2003 Oct; 17(4): 252-62.
4. Toy P, Gajic O. Transfusion-related acute lung injury. Anesth Analg. 2004 Dec; 99(6): 1623-4.

Complications and management of massive transfusion in a table format

Adapted with permission from the Transfusion Manual for Nursing Units from St. Michaels Hospital, Toronto Ontario. Canada.

Hemostatic Abnormalities in Massive Transfusion

Description 

Clinically significant haemostatic abnormalities complicating massive transfusion can occur due to dilution and depletion of coagulation proteins and platelets.

Decreased platelet counts may complicate massive transfusion of components which do not contain platelets. Thrombocytopenia is usually not as severe as predicted by simple hemodilution. With red blood cell replacement for loss of up to one blood volume, clotting factor levels may be reduced to 25% of normal and PT INR measurements may be slightly prolonged without clinical coagulopathy.

50% of massively transfused patients develop an INR >2.0 and about 33% have thrombocytopenia with a platelet count <50 x 109/L. Disseminated intravascular coagulation (DIC) occurs in 5-30% of massively transfused trauma patients.

Further Reading

Metabolic Complications of Massive Transfusion

Description

Potential metabolic abnormalities secondary to massive transfusion include hypocalcemia, hypomagnesemia, metabolic alkalosis, hyperkalemia or hypokalemia.

Citrate Toxicity: hypocalcemia, hypomagnesemia, metabolic alkalosis

Blood components are anticoagulated with sodium citrate. It is rapidly metabolized by the liver, and a normothermic adult can tolerate the citrate in a unit of plasma or several units of red blood cells given every five minutes. When transfused, citrate may bind with circulating ionic calcium and magnesium. During massive transfusion, the capacity of the liver to metabolize citrate may be overwhelmed, and potentiated by hypothermia or hypotension, particularly in the presence of underlying liver disease, leading to hypocalcemia and/or hypomagnesemia. Metabolic alkalosis may also develop secondary to the accumulation of bicarbonate, the metabolic by-product of citrate.

Metabolic acidosis

Metabolic acidosis is rare. It may be caused from the acid pH of blood products, and aggravated by lactic acidosis seen in patients with tissue hypoxia.

Hyperkalemia or Hypokalemia

Potassium release from red cells increases during storage, and after irradiation. Levels of up to 80 mmol/L may be reached in a unit of red blood cells. Massive transfusion may lead to hyperkalemia, which can cause cardiac arrhythmias or myocardial depression. Young infants are the most susceptible patients, particularly if stored blood is transfused rapidly into a central line.

Paradoxically, hypokalemia has also been described with massive transfusion. Possible causes include metabolic alkalosis secondary to citrate metabolism and re-accumulation of potassium in transfused potassium-depleted RBCs.

Further Reading

Hypothermia due to Massive Transfusion

Red blood cells are stored at 2 - 6 °C. Blood does not require warming for most routine transfusions. However, rapid, massive transfusion may result in clinically significant hypothermia (body temperature <35 °C.), particularly in paediatric patients. In addition, cardiac arrhythmias are reported to be increased in anaesthetized patients receiving massive transfusions of cold blood.

The incidence of transfusion-induced hypothermia associated with massive transfusion is unknown.

Further Reading

Massive Transfusion: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Popovsky, MA, ed., Transfusion Reactions, Second Edition, Bethesda MD, AABB Press, 2001, Ch 13: Complications of Massive Transfusion pp 339-357.
2. Brecher, ME, ed., AABB Technical Manual, 14th ed., Bethesda MD, AABB Press, 2002, Ch 21: Blood Transfusion practice pp 476-478.
3. Gutierrez G, Reines HD, Wulf-Gutierrez ME. Clinical review: hemorrhagic shock. Crit Care. 2004 Oct;8(5): 373-81. [Medline]
4. Mintz, PD, ed., Transfusion Therapy, Clinical Principles and Practice, Bethesda MD, AABB Press, 2001; Ch 9 Transfusion in Surgery and Trauma pp 183-190.
5. Hardy J-F et al. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anesth 2004; 51:4 ; 293-310.

Treatment - Adverse Interactions with Medications and Solutions

Treatment of medication/solution interaction with a blood component is usually similar to treatment of non-immune hemolytic transfusion reactions.

Reporting - Adverse Interactions with Medications and Solutions

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Clinical Presentation - Air Embolism

Patients with clinically significant air embolism may experience complete circulatory collapse. Cyanosis and petechiae may be observed. Dramatic falls in arterial blood pressure, elevation of central venous pressure (CVP), arrhythmias, and ECG changes may indicate the presence of severe pulmonary air embolism. A characteristic cog wheel or mill wheel murmur may be heard over the precordium.

A patient at risk for air embolism who experiences the above signs and symptoms should be investigated and treated rapidly.

Investigation - Air Embolism

The urgency of the situation may allow little time for investigation. Auscultatory findings by esophageal stethoscope, or Doppler examination, if immediately available, may aid the diagnosis. Arterial and central venous pressures, and end-tidal CO2 levels, as well as clinical suspicion in a setting at high risk for this complication will aid the diagnosis.

Treatment - Air Embolism

Mechanical ventilation with 100% oxygen, positive end-expiratory pressure, pharmacologic circulatory support, and external cardiac massage may be required. Positioning the patient in the left lateral decubitus position, as well as attempting to aspirate the air from the central venous system may be tried but are often ineffective.

Reporting - Air Embolism

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Air Embolism

Prevention is paramount in this potentially fatal complication. Due care and attention when administering intravenous fluids and blood products, including the setting of intraoperative cell salvage, should completely eliminate air embolism as a risk of transfusion.

Air Embolism: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Popovsky MA, ed., Transfusion Reactions, Second Edition, Bethesda MD, AABB Press, 2001, p351; 285, 286.
2. Brecher, ME, ed., AABB Technical Manual, 14th ed., Bethesda MD, AABB Press, 2002, p 588, 601
3. Linden JV, Kaplan HS, Murphy MT. Fatal air embolism due to perioperative blood recovery. Anesth Analg 1997, 84: 422-6.
4. Breen PH, Hong A. Beware of air in the blood pump. Anesth Analg 2000; 91:1038.

Clinical Presentation - Circulatory Overload

Circulatory overload begins within hours of transfusion. General symptoms include headache, dry cough, and chest pain. More specific signs and symptoms include:

• coughing
• wheezing
• dyspnea
• cyanosis
• tachycardia
• hypertension
• pedal edema
• pulmonary edema

Mechanism

Very young or very old patients with underlying congestive heart failure or chronic anemia and an expanded blood volume are most at risk. When too much blood is transfused too quickly, these patients cannot handle the increased volume and develop heart failure and acute pulmonary edema.

Investigation - Circulatory Overload

Transfusion services should have clear policies describing the required investigation for transfusion complications. An example of an immediate investigation shows steps that could be used to investigate any immediate transfusion reaction.

This type of complication is rarely reported to the hospital transfusion service and laboratory investigation is therefore rare unless the symptoms are severe.

Circulatory overload needs to be differentiated from other causes of acute respiratory distress such as anaphylaxis and TRALI as the management of future transfusion is very different in these complications. Both anaphylaxis and TRALI are characterized by hypotension (moderate to severe); TRALI symptoms include a fever and pulmonary edema; anaphylaxis includes a rash but not pulmonary edema.

Treatment - Circulatory Overload

Treatment focuses on providing oxygen support and reducing plasma volume with diuretics (and phlebotomy if symptoms persist).

Pulmonary edema should be promptly and aggressively treated, and infusion of colloid preparations, including plasma in cellular components, reduced to a minimum.

Initial treatment includes

• early recognition;
• stopping the transfusion;
• not transfusing further units;
• keeping the IV line open with saline;
• placing the patient in a sitting position
• initiating early treatment based on symptoms under direction of a physician.

Reporting - Circulatory Overload

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Circulatory Overload

Prevention consists of transfusing at-risk patients slowly and with blood components in the most concentrated form.

Except for replacement of acute, massive blood loss, infusion rates should ordinarily be no greater than 2 - 4 mL per kg body weight per hour, and for patients at known risk of hypervolemia, a rate no faster than 1 mL/kg/hr is advisable.

Circulatory Overload: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Popovsky MA. Circulatory overload. In: Popovsky MA, ed. Transfusion reactions, 2nd ed. Bethesda, MD: AABB Press;2001. p. 255-60.
2. Popovsky MA, Audet Am, Andrzejewski JRC. Transfusion-associated circulatory overload in orthopedic surgery patients: a multi-institutional study. Immunohematol. 1996 Jun; 12(2): 87-9.[Medline]

Clinical Presentation - Isolated Hypotensive

Symptoms typically appear within minutes of initiation of transfusion. Hypotension may be the only symptom and rapid response is seen once the transfusion is stopped. Other symptoms, if present, are minor.

Signs and symptoms include:

Primary

• A hypotensive episode is defined as a drop in systolic and/or diastolic blood pressure of greater than 30 mm Hg.

Secondary (±)

• Dyspnea
• Urticaria
• Flushing
• Pruritis
• Diarrhea
• Nausea

Mechanism

Thought to involve the generation of bradykinin and/or the metabolite des-Arg3-BK. Plasma contact with a negatively charged surface activates the contact system of plasma leading to the generation of plasma kallikrein that cleaves high molecular weight kininogen to liberate the nonapeptide bradykinin which is further metabolized. When ACE inhibitor is present the transformation of BK to des-Arg3-BK is inhibited. For reactions that occur in the absence of negatively charged bedside leukoreduction filters and/or ACE inhibitor therapy, unidentified mechanisms not involving BK generation may be responsible.

Investigation - Isolated Hypotensive

Transfusion services should have clear policies describing the required investigation for transfusion complications. An example of an immediate investigation shows steps that could be used to investigate any immediate transfusion reaction.

A hypotensive reaction needs to be differentiated from other types of transfusion reaction that may have hypotension as a symptom. These include but are not limited to bacterial contamination, acute hemolytic, anaphylactic, TRALI and/or allergic reactions.

Fever does not occur with a primary hypotensive reaction. If symptoms do not subside immediately after discontinuing the transfusion, a chest x-ray should be considered to exclude TRALI, and blood cultures to exclude a septic transfusion reaction. Consideration must also be given to whether the hypotensive episode was unrelated to the transfusion or an underlying medical condition. Only after all other reactions and reasons are eliminated should hypotensive transfusion reaction be considered.

Treatment - Isolated Hypotensive

Initial treatment includes:

• early recognition
• stopping the transfusion immediately
• not transfusing further units until the cause is resolved
• keeping the IV line open with saline
• initiating early treatment based on symptoms and as directed by a physician

An Isolated Hypotensive Transfusion Reaction is treated with a bolus of saline to restore blood pressure.

Reporting - Isolated Hypotensive

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Isolated Hypotensive

If the implicated transfusion was administered through a negatively charged bedside leukoreduction filter, use of other types of filters or prestorage leukoreduction should be considered.

In therapeutic apheresis procedures, consideration should be given to discontinuing ACE inhibitor therapy for 24 hours to several days depending on the half-life of the ACE inhibitor used.

Isolated Hypotensive: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Arnold DM, Molinaro G, Warkentin TE, DiTomasso J, Webert KE, Davis I, Lesiuk L, Dunn G, Heddle NM, Adam A, Blajchman MA. Hypotensive transfusion reactions can occur with blood products that are leukoreduced before storage. Transfusion. 2004 Sep; 44(9): 1361-6. [Medline]
2. Cyr M, Eastlund T, Blais C Jr, Rouleau JL, Adam A. Bradykinin metabolism and hypotensive transfusion reactions. Transfusion. 2001 Jan.41(1):136-50.[ Full text ]
3. Cyr M, Hume HA, Champagne M, Sweeney JD, Blais C Jr, Gervais N, Adam A. Anomaly of the des-Arg9-bradykinin metabolism associated with severe hypotensive reactions during blood transfusions: a preliminary study. Transfusion 1999 Oct. 39(10):1084-8. [ Full text ] [ Medline ]
4. Hume HA, Adam A. In: Popovsky M, editor. Transfusion reactions, 2nd ed. Arlington, VA: AABB Press; 2001. p. 212-233.
5. Hume HA, Popovsky MA, Benson K, Glassman AB, Hines D, Oberman HA, et al. Hypotensive reactions: a previously uncharacterized complication of platelet transfusion? Transfusion. 1996 Oct. 36(10):904-9. [ Medline ]

Clinical Presentation - Delayed Hemolytic Transfusion Reactions

DHTR may go undetected as the symptoms may be mild and subclinical. Death is a rare event but has been reported. Red cell destruction is usually by extravascular hemolysis (EVH). When present, typical signs and symptoms include:

• fever with or without chills
• unexplained drop in hemoglobin and hematocrit
• transient jaundice due to elevated serum bilirubin

Mechanism

Upon re-stimulation by red cells positive for the corresponding antigen to the patient's weak, undetectable alloantibody, memory B cells differentiate into antibody-producing plasma cells. As new IgG antibody is produced, it sensitizes transfused donor cells with the corresponding antigen. The IgG-sensitized donor cells are removed by EVH mainly in the spleen.

Investigation of a Delayed Hemolytic Transfusion Reaction (DHTR)

Transfusion services should have clear policies describing the required investigation of transfusion complications.

A Delayed Hemolytic Transfusion Reaction is seen days to weeks post-transfusion, and usually detected serologically with the direct antiglobulin test (DAT) showing a positive result.

Depending on the results of the initial investigation, the transfusion service will perform follow-up serologic testing according to its own policies and procedures. Some examples are outlined below.

NOTE: The expected results in a DHTR include the appearance of a"new" antibody and development of a positive DAT, although these may not always be detectable depending on the time of testing.

Positive Direct Antiglobulin Test (DAT)

To be valid, a DAT should be performed on an (EDTA) specimen. An EDTA specimen will prevent complement from binding in vitro due to a harmless cold autoantibody such as autoanti-I, an autoantibody, which many people have. If the DAT done on the patient's post-transfusion EDTA blood sample is positive:

• perform a DAT on the pre-transfusion blood sample for comparison (unless already done). If the DAT on the pre-transfusion specimen is also positive, and of approximately the same strength, the positive DAT on the post-transfusion specimen is not suggestive of a hemolytic transfusion reaction.

If the DAT on the pre-transfusion specimen is negative, a more complete investigation should be done, an example of which follows.

Monospecific DATs

If the post-transfusion DAT is positive with polyspecific antiglobulin serum, the DAT should be repeated with monospecific anti-IgG and anti-C3b/-d to determine the substances sensitizing the patient's red cells. The major purpose is to assess if an elution is worthwhile to identify antibodies that may be sensitizing the patient's cells.

Elution

An elution should be performed if a DAT using a monospecific anti-IgG is positive. The eluate is then tested with a panel to identify the antibodies involved.

Antigen type

If a specific antibody is identified, the patient's pre-transfusion specimen should be phenotyped for the antigen(s) corresponding to the antibody(ies) identified.

Treatment of a Delayed Hemolytic Transfusion Reaction (DHTR)

Treatment of a delayed hemolytic transfusion reaction is usually not required unless anemia is severe enough to require treatment.

Alternatives to transfusion should be explored whenever possible.

Reporting of a Delayed Hemolytic Transfusion Reaction (DHTR)

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention of Delayed Hemolytic Transfusion Reactions (DHTR)

Preventing DHTR may be impossible if the patient's antibody is too weak to be detected by routine antibody detection methods. However there are many standard procedures and protocols that transfusion services can use to minimize this complication. Some examples include:

• Performing a history check to identify patients that have existing antibodies that may have weakened over time.
   
• Using sensitive antibody detection methods.
   
• Using antibody screen cells from donors who between them are homozygous for all of the common antigens that are expressed more strongly on homozygous RBCs (i.e., show a "dosage effect"). Such blood groups include Rh (C,E,c,e), Kidd (Jka, Jkb), Duffy (Fya, Fyb), MNSs.
   
• For patients who have been transfused or pregnant in the last three months, using crossmatch specimens that are no older than three days (where the date of collection is day one).
   
• For patients who have clinically significant antibodies, antigen phenotyping donors using commercial antisera, followed by serologic crossmatching of antigen-negative donors using an antiglobulin test or equivalent method, even when the antibody (antibodies) are not currently detectable.
   
• For patients with known clinically significant antibodies, assuring, on each pre-transfusion sample tested, that the evaluation for the presence of additional (new) clinically significant antibodies has been correctly performed (i.e., that appropriately phenotype tested RBCs have been selected to investigate this possibility).
   
• For patients with clinically significant antibodies, issuing, via the patient's physician, antibody cards that specify the antibodies present. Patients can carry these cards and alert medical staff as appropriate.

Delayed Hemolytic Transfusion Reactions: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Davenport RD. Hemolytic transfusion reactions. In: Popovsky MA, ed. Transfusion reactions, 2nd ed. Bethesda, MD: AABB Press; 2001. p.1-44.
2. Heddle NM, Soutar RL, O'Hoski PL, Singer J, McBride JA, Ali MA, Kelton JG. A prospective study to determine the frequency and clinical significance of alloimmunization post-transfusion. Br J Haematol 1995 Dec.;91(4):1000-5. [ Medline ]
3. Ness PM, Shirey RS, Weinstein MH, King KE. An animal model for delayed hemolytic transfusion reactions. Transfus Med Rev 2001 Oct.;15(4):305-17. [ Medline ]
4. Pineda AA, Vamvakas EC, Gorden LD, Winters JL, Moore SB. Trends in the incidence of delayed hemolytic and delayed serologic transfusion reactions. Transfusion 1999 Oct.;39(10):1097-103. [ Full text ] [ Medline ]
5. Schonewille, H., Haak, H.L., van Zijl, A.M. Alloimmunization after blood transfusion in patients with hematologic and oncologic diseases. Transfusion 1999 Jul.;39(7):763-71. [ Full text ] [ Medline ]
6. Schonewille H, Haak HL, van Zijl AM. RBC antibody persistence. Transfusion 2000 Sep.;40(9):1127-31. [ Full text ] [ Medline ]
7. Vamvakas EC, Pineda AA, Reisner R, Santrach PJ, Moore SB. The differentiation of delayed hemolytic and delayed serologic transfusion reactions: incidence and predictors of hemolysis. Transfusion 1995 Jan.;35(1):26-32. [ Medline ]

Clinical Presentation - Post-Transfusion Purpura (PTP)

Signs, symptoms, and sequelae include:

• severe thrombocytopenia (< 10 x 109/L in 80% of cases)
• mucous membrane bleeding
• epistaxis
• GI hemorrhage
• urinary tract bleeding
• intracranial hemorrhage
• occasionally accompanied by fever, chills or bronchospasm

Mechanism

The mechanism of post transfusion purpura (PTP) is unclear but seems related to the platelet-specific alloantibody formed from prior transfusion/pregnancy and triggered in some way by the recent transfusion. Of the many hypotheses proposed to explain the syndrome, one is that autoantibody forms in conjunction with the platelet alloantibody and so that both transfused allogeneic and recipient autologous platelets are destroyed.

Investigation - Post-Transfusion Purpura (PTP)

Transfusion services should have clear policies describing the required investigation for transfusion complications.

In Post-Transfusion Purpura (PTP) laboratory tests usually reveal:

• Severe thrombocytopenia
• Normal red cell morphology
• Antibody with specificity for HPA-1a (or other platelet-specific antibody)
• HPA-1a negative phenotype or platelet genotype of HPA-1b/1b (or antigen-negative phenotype/genotype for another platelet specific antigen)

Clinically, PTP needs to be differentiated from Immune Thrombocytopenia Purpura (ITP), Thrombotic Thrombocytopenic Purpura (TTP), drug-induced thrombocytopenia, bacterial sepsis, Disseminated Intravascular Coagulation (DIC), and bone marrow failure. It should also be differentiated from otherwise uncomplicated alloimmunization to platelet specific antigens (See Further Reading- Popoksky MA).

Treatment - Post-Transfusion Purpura (PTP)

Treatment may include:

• corticosteroids
• intravenous immune globulin (IVIG)
• plasma exchange (for patients refractory to IVIG therapy).

Warning: Affected women are at risk of Neonatal Alloimmune Thrombocytopenia (NAIT) in future pregnancies and should be counselled accordingly.

Reporting - Post-Transfusion Purpura (PTP)

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Post-Transfusion Purpura (PTP)

Prevention of initial reaction is not possible.

Although recurrence is rare, patients with a documented history of Post Transfusion Purpura (PTP) should receive, if possible, blood components that are antigen-negative for the platelet antibody.

Warning: Affected women are at risk of Neonatal Alloimmune Thrombocytopenia (NAIT) in future pregnancies and should be counselled accordingly.

Post-Transfusion Purpura (PTP): Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Loren AW, Abrams CS. Efficacy of HPA -1a (P1A1)-negative platelets in a patient with post-transfusion purpura. Am J Hematol. 2004 Jul; 76 (3); 258-62. [Medline]
2. McFarland J. Posttransfusion purpura. In: Popovsky MA, ed. Transfusion reactions, 2nd ed. Bethesda, MD: AABB Press; 2001. p. 187-212.
3. von Baeyer H. Plasmapheresis in immune hematology: review of clinical outcome data with respect to evidence-based medicine and clinical experience. Ther Apher Dial. 2003 Feb; 7(1): 127-40. Review. [Medline]

Clinical Presentation - Transfusion-Associated Graft-vs- Host Disease (TA-GVHD)

The clinical syndrome consists of fever, skin rash, diarrhea, hepatic dysfunction, and bone marrow aplasia, typically appearing eight to ten days after transfusion.
The outcome has a high fatality rate, with hemorrhage and infection as the most common causes of death.

Mechanism

TA-GVHD results when transfused T lymphocytes present in cellular blood components engraft, multiply, and react against the tissues of the recipient.

Investigation - Transfusion-Associated Graft-vs- Host Disease (TA-GVHD)

Transfusion services should have clear policies describing the required investigation transfusion complications.

An investigation will only be initiated if the treating physician is aware of this possibility in a susceptible patient with a clinical picture suggestive of Transfusion-Associated Graft vs. Host Disease (TA-GVHD).

The investigation begins with the confirmation of the presence of GVHD. This is a pathologic diagnosis requiring a skin or intestinal biopsy. If GVHD is present, further studies should be performed to confirm the engraftment of donor lymphocytes.

Reporting - Transfusion-Associated Graft-vs- Host Disease (TA-GVHD)

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Transfusion-Associated Graft-vs- Host Disease (TA-GVHD)

Currently the only method of preventing transfusion-associated graft versus host disease (TA-GVHD) is to gamma irradiate cellular components at risk of causing TA-GVHD or destined for at risk recipients. Current techniques to leukoreduce cellular blood components are not adequate to prevent TA-GVHD

• Irradiated blood is prepared by exposing the component to a source of gamma irradiation. To eliminate the proliferative capacity of leukocytes, the central midplane of the canister should receive 2500 cGy and the lowest dose delivered to any portion of the canister should be 1500 cGy.

Canadian Blood Services produces the following gamma irradiated products:

• Red Blood Cell products, LR
• Platelets, LR
• Platelets Apheresis, LR

Gamma irradiation, in the doses recommended for the prevention of TA-GVHD, does not affect the function of platelets. However, it does result in some damage to the erythrocyte membrane so that the permitted storage date of red cell concentrates is 28 days following irradiation (or the usual expiry date, whichever is shorter). There is also a more rapid accumulation of potassium in the extracellular fluid of the red cell concentrates. For this reason, for neonates and young children, it is preferable to gamma irradiate red cell components as close to the time of transfusion as possible. In these patients, if the units have not been irradiated just prior to transfusion, removal of extracellular fluid, (to reduce risks associated with high plasma potassium), may be considered.

Transfusion-Associated Graft-vs- Host Disease (TA-GVHD): Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Food and Drug Administration. Gamma Irradiation of Blood Products. CBER, FDA 1993.
2. Guidelines for Irradiation of Blood and Blood Components. New York State Council on Human Blood and Transfusion Services. June 9, 1993.
3. Luban NL. Irradiation for neonatal and pediatric transfusion in: Herman JH, Manno CS. Pediatric Transfusion Therapy. Bethesda MD: AABB Press; 2002: 147-169.
4. Luban NL. Prevention of transfusion-associated graft versus host disease by inactivation of T cells in platelet components. Semin Hematol 2001 Oct;38 (4 Suppl 11):34-45. [ Medline ].
5. McMilin KD, Johnson RL. HLA homozygosity and the risk of related-donor transfusion-associated graft versus host disease. Transfus Med Rev 1993 Jan; 7(1):37-41. [ Medline ].
6. Nollet KE, Holland PV. Toward a coalition against transfusion-associated GVHD. Transfusion 2004; 43 (12):1655-7. [ Full Text ] [ Medline ]
7. Triulzi Darrell J. Transfusion Support in Solid-Organ Transplantation. Institute for Transfusion Medicine. Transfusion Medicine Update. April 2001.
8. Webb IJ, Anderson KC. Transfusion-associated graft versus host disease. In: Popovsky MA, ed. Transfusion reactions, 2nd ed. Bethesda, MD: AABB Press; 2001. 171-82.
9. Wong ECC, Irradiated Products in: Hillyer CD, Strauss RG, Luban NLC. Handbook of Pediatric Medicine. San Diego CA: Elsevier Academic Press; 2004: 101-112.

Clinical Presentation - Red Cell Alloimmunization

Occasionally RBC alloimmunization may present as an immediate or delayed hemolytic transfusion reaction. However, usually RBC alloimmunization is clinically silent and discovered only during subsequent pretransfusion testing or routine testing during pregnancy.

If antibody testing is performed in the days or weeks following RBC transfusions, newly formed RBC antibodies may be detected, or if an anamnestic response has occurred, a positive DAT (with or without the presence of antibody in the serum/plasma) may be detected. In the latter case, the alloantibody can be eluted from the patient’s red cells.

In a pregnant woman, if prenatal RBC antibody testing is not performed as recommended, it is possible that the first manifestation could be hemolytic disease of the fetus or newborn.

Investigation - Red Cell Alloimmunization

Transfusion services should have clear policies describing the required investigations for transfusion complications.

Laboratory investigation of RBC alloimmunization is initiated when a patient is tested subsequent to transfusion or pregnancy, and found to have a positive antibody screen and/or positive DAT.

Depending on the results of the initial investigation, the transfusion service will perform follow-up serologic testing according to its own policies and procedures. Some examples are outlined below.

NOTE: The expected results include the appearance of a "new" positive antibody screen and negative direct antiglobulin test (DAT) unless the patient has been recently transfused in which case the DAT may also be positive. In patients with known red cell antibodies a change in strength or pattern of the antibody screen is suggestive of additional antibody formation.

Antibody identification

If a new or unexpected antibody is found in the antibody screen, it must be identified prior to any subsequent RBC transfusion. If the DAT is positive and an alloantibody (as opposed to an autoantibody) is suspected, an elution should also be performed.

Antigen type

If a specific antibody is identified, the patient's pre-transfusion specimen should be phenotyped for the antigen(s) corresponding to the antibody(ies) identified.

NOTE: If the patient was transfused with a product such as intravenous immune globulin (IVIG) or a large dose of Rh immune globulin (RhIG), e.g., to treat Immune Thrombocytopenia Purpura (ITP), suspect passive antibodies.

Treatment - Red Cell Alloimmunization

Transfusion

All future RBC transfusions should be antigen negative for each clinically significant antibody that the patient has formed.

Depending on the number and type of antibodies, delays in the provision of compatible blood could occur depending on the services and blood supply at the hospital transfusion service. Therefore to the extent possible, RBC transfusions for such patients should be planned in advance. Occasionally it may even be necessary to arrange for the provision of stored frozen autologous or compatible allogeneic RBCs.

Although debate exists about its merits, for selected high-risk patients with transfusion-dependent diseases (e.g., sickle cell anemia, thalassemia, etc) some transfusion services phenotype patients and provide phenotypically matched donor RBC, even to those patients without alloantibodies (i.e., to prevent the formation of antibodies). There is general agreement that this is useful for Rhesus and Kell blood group antigens in these groups of patients, but debate exists about its merits for more extensive phenotyping.

Pregnancy 

All pregnant women with RBC antibodies that may cause haemolytic disease of the foetus/newborn should be referred to an obstetrician experienced in the care of this disorder.

Common red cell (RBC) antibodies that may be associated hemolytic disease of the fetus or newborn (HDFN)*, according to blood group system and antigen specificity

* This list includes only the most common RBC antibodies; it is not exhaustive. For less common antibodies refer to: Issit PD, Anstee DJ. Applied Blood Group Serology, 4th ed. Montgomery Scientific Publications, Durham NC, 1998.

Reporting - Red Cell Alloimmunization

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Prevention - Red Cell Alloimmunization

Alloimmunization cannot be entirely prevented except by transfusions from an identical twin or by autologous transfusions. Leukoreduction of cellular components reduces the incidence of alloimmunization to leukocyte antigens but it is unlikely that it has a major impact on the incidence of RBC alloimmunization.

Preventing RBC antibody formation is not practical for most patients and, for many, alloimmunization causes no serious sequelae. However, prevention of RBC alloimmunization is important in women of child bearing age, and for some patients at risk of serious haemolytic transfusion reactions and/or chronic transfusion requirements, e.g., patients with sickle cell anemia.

The administration of Rh Immune Globulin (RhIg) to D-Negative mothers delivering a D- positive infant has been shown to be a highly effective method for reducing the incidence of Hemolytic Disease of the Fetus and Newborn (HDFN) due to anti-D. When RhIg is administered within 72 hours of a full-term delivery of a D-positive infant by a D-negative mother, the incidence of alloimmunization is decreased from 12-13 per cent to 1-2 per cent. When RhIg is also administered at 28 weeks, the incidence of alloimmunization is further decreased to 0.1 per cent. (See Further Reading)

In order to prevent RBC alloimmunization against other RBC antigens, in females at or prior to child-bearing age, for elective surgery likely to require RBC transfusion, autologous rather than allogeneic RBC transfusion should be used if possible. Finally, spouses of women of child-bearing age should not be directed donors for these women (and, in addition, CBS policies do not in any event permit this).

If a D-negative female patient, at or prior to child-bearing age, is transfused with platelets that are either from a D-positive donor or a donor of unknown D status, then an appropriate dose of RhIg should be administered (10-12 µg/mL of transfused RBCs). Some Transfusion Medicine services will administer anti-D to all patients in this circumstance.

For selected high-risk patients with transfusion-dependent diseases such as sickle cell anemia and thalassemia, some transfusion services antigen phenotype patients and provide phenotypically matched donor RBC in an attempt to prevent RBC alloimmunization. There is general agreement that this is useful for Rhesus and Kell blood group antigens but debate exists about its merits for more extensive phenotyping. (See Telen in Further Reading).

Red Cell Alloimmunization: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Blumberg N, Heal JM, Gettings KF. WBC reduction of RBC transfusions is associated with a decreased incidence of RBC alloimmunization. Transfusion. 2003 Jul;43(7):945-52. [Full Text] [ Medline ]
2. Friedman DF, Lukas MB, Jawad A, Larson PJ, Ohene-Frempong K, Manno CS. Alloimmunization to platelets in heavily transfused patients with sickle cell
   disease. Blood. 1996 Oct 15;88(8):3216-22.
3. Issitt PD. Race-related red cell alloantibody problems. Br J Biomed Sci 1994 Jun;51(2):158-67. [ Medline ]
4. Kiefel V, Konig C, Kroll H, Santoso S. Platelet alloantibodies in transfused patients. Transfusion. 2001 Jun;41(6):766-70. [ Full text ] [Medline ]
5. Olujohungbe A, Hambleton I, Stephens L, Serjeant B, Serjeant G. Red cell antibodies in patients with homozygous sickle cell disease: a comparison of patients in Jamaica and the United Kingdom. Br J Haematol 2001 Jun;113(3):661-5. [ Medline ]
6. Reid ME, Oyen R, Marsh WL. Summary of the clinical significance of blood group alloantibodies. Semin Hematol 2000 Apr;37(2):197-216.
7. Schonewille, H., Haak, H.L., van Zijl, A.M. Alloimmunization after blood transfusion in patients with hematologic and oncologic diseases. Transfusion 1999 Jul; 39(7): 763-71. [ Full text ] [ Medline ]
8. Schonewille H, Haak HL, van Zijl AM. RBC antibody persistence. Transfusion 2000 Sep;40(9):1127-31. [ Full text ] [ Medline ]
9. Seftel MD, Growe GH, Petraszko T, et al. Universal prestorage leukoreduction in Canada decreases platelet alloimmunization and refractoriness. Blood, 2004,Jan; 103 (1), 333-39.
10. Singer S T, Wu V, Mignacca R, Kuypers FA, Morel P, Vichinsky EP. Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly Asian descent. Blood, 2000 15 Nov;96(10): 3369-73.
11. Strauss RG, Johnson K, Cress G, Cordle DG. Alloimmunization in preterm infants after repeated transfusions of WBC-reduced RBCs from the same donor. Transfusion. 2000 Dec;40(12):1463-8. [ Full Text ] [ Medline ]
12. Telen MJ. Principles and problems of transfusion in sickle cell disease. Semin Hematol. 2001 Oct;38(4):315-23.
13. van de Watering L, Hermans J, Witvliet M, Versteegh M, Brand A. HLA and RBC immunization after filtered and buffy coat-depleted blood transfusion in cardiac surgery: a randomized controlled trial. Transfusion. 2003 Jun;43(6):765-71. [Full Text ] [ Medline ]
14. Winters JL, Pineda AA, Gorden LD, Bryant SC, Melton LJ III, Vamvakas EC, et al. RBC alloantibody specificity and antigen potency in Olmstead County, Minnesota. Transfusion, 2001 Nov;41(11): 1413-20. [ Full text ] [Medline ]

Investigation - Transfusion-Transmissible Diseases

Investigation of a possible transfusion-transmissible disease, upon report of the infection of a recipient, includes the following:

• A history of transfusion events that include all blood components, donation dates and transfusion dates.
• Report this information to the blood supplier who initiates testing of all donors.
• A lookback of the donors’ previous donations and an investigation are initiated in accordance with established procedures

Reporting - Transfusion-Transmissible Diseases

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Transfusion-Transmissible Diseases: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Blajchman MA, Goldman M, Freedman JJ, Sher GD. Proceedings of a consensus conference: prevention of post-transfusion CMV in the era of universal leukoreduction. Transfus Med Rev. 2001 Jan.;15(1):1-20.
2. Blajchman MA, Goldman M, Webert KE, Vamvakas EC, Hannon J, Delage G, Proceedings of a consensus conference: the screening of blood donors for variant CJD. Transfus Med Rev. 2004 Apr; 18(2): 73-92.
3. Busch MP, Kleinman SH, Nemo GJ, Current and emerging infectious risks of blood transfusions. JAMA 2003; 289: 959-62.
4. Callum JL, Coovadia AS, Thomson A, Dewsbury F, Pinkerton PH. Creutzfeldt-Jakob disease targeted lookback. Transfusion 1999 May;39(5):540-1. [ Full text ] [ Medline ]
5. Chiavetta JA, Escobar M, Newman A, HE Y, Driezen P, Deeks S, Hone DE, O’Brien SF, Sher G. Incidence and estimated rates of residual risk for HIV, hepatitis C, hepatitis B and human T-cell lymphotropic viruses in blood donors in Canada, 1990-2000. CMAJ. 2003 Oct 14; 169(8): 767-73.
6. Dodd RY, Notari EP IV, Stramer SL. Current prevalence and incidence of infectious disease markers and estimated window-period risk in the American Red Cross blood donor population. Transfusion 2002; 42: 975-9.
7. Gregori L, McCombie N, Palmer D, Birch P, Sowemimo-Coker SO, Giulivi A, Rohwer RG. Effectiveness of leucoreduction for removal of infectivity of transmissible spongiform encephalopathies from blood. Lancet. 2004 Aug 7:364(9433): 529-31. [Medline]
8. Hart J, Leier B, Nahirniak S. Informed consent for blood transfusion: should the possibility of prion risk be included? Transfus Med Rev. 2004 Jul; 18(3): 177-83. [Medline]
9. Kleinman C, Chan P, Robillard P. Risks associated with transfusion of cellular blood components in Canada. Transfus Med Rev 2003 Apr.;17(2):120-62.
10. Laupacis A, Brown J, Costello B, Delage G, Freedman J, Hume H, et al. Prevention of posttransfusion CMV in the era of universal WBC reduction: a consensus statement. Transfusion. 2001 Apr.;41(4):560-9. [ Full text ] [ Medline ]
11. Llewelyn CA, Hewitt PE, Knight RS, Amar K, Cousens S, Mackenzie J, Will RG. Possible transmission of variant Creutzfeldt-jakob disease by blood transfusion. Lancet. 2004 Feb 7:363 (9407):417-21. [Medline]
12. McCullough J, Anderson D, Brookie D, Bouchard JP, Fergusson D, Joly J, Kenny N, Lee D, Megann H, Page D, Reinharz D, Williams JR, Wilson K, Consensus conference on vCJD screening of blood donors: report of the panel. Transfusion. 2004 May; 44(5): 675-83.
13. Orton SL, Stramer SL, Dodd, RY, Alter, MJ. Risk factors for HCV infection among blood donors confirmed to be positive for the presence of HCB RNA and not reactive for the presence of anti-HCV. Transfusion 2004; 44: 275-81.
14. Pealer LN, Martin AA, Petersen LR, et al. Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J. Med 2003; 349: 1236-45.
15. Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet. 2004 Aug 7; 364(9433): 527-9. [Medline]
16. Pincock S. Government confirms second case of vCJD transmitted by blood transfusion. BMJ. 2004 Jul 31; 329(7460): 251. [Medline]
17. Preiksaitis JB. The cytomegalovirus - "safe" blood product: Is leukoreduction equivalent to antibody screening? Transfus Med Rev 2000;14:112-36. [ Medline ]
18. Regan FAM, Hewitt P, John A J Barbara JAJ, Contreras M. Prospective investigation of transfusion transmitted infection in recipients of over 20 000 units of blood. Br Med J 2000;320: 403-6.
19. Stramer, SL, Glynn, SA, Kleinman, SH, Strong, DM, Caglioti, S., Wright, DJ, Dodd, RY, Busch, MP. Detection of HIV-1 and HCV Infections among Antibody-Negative Blood Donors by Nucleic Acid-Amplification Testing. N Engl J Med. 2004, August: 760-768.
20. Update: West Nile virus screening of blood donations and transfusion-associated transmission-United States, 2003. MMWR Morb Mortal Wkly Rep 2004, 53: 281-4.
21. Wilson K, Ricketts MN. Transfusion transmission of vCJD: a crisis avoided? Lancet. 2004 Aug 7; 364 (9433): 477-9. [Medline]
22. Zou S, Notari EP, Stramis SL, Wahab, F, Musaui F, Dodd RY. For the ARCNET Reseach Group. Patterns of age-and sex-specific prevalence of major blood-borne infections in United States blood donors, 1995 to 2002: American Red Cross blood donor study. Transfusion 2004 November; 44(11): 1640-47. [Medline]

Clinical Presentation - Transfusional Iron Overload

If untreated, sequelae include:

• congestive cardiomyopathy and/or cardiac arrhythmias
• liver damage eventually resulting in cirrhosis
• endocrine dysfunction affecting:
  - the pancreas (leading to diabetes mellitus)
  - the pituitary gland (causing short stature and hypogonadism)
  - the parathyroid (causing hypocalcemia)

Mechanism

With repeated transfusions iron accumulates, reflecting the retention of the heme iron from the transfused red cells after they become senescent and are destroyed by cells of the monocyte-macrophage system.

Iron toxicity is believed to be due to free radical damage to tissues induced by iron that is circulating unbound to plasma proteins such as transferrin.

Treatment - Transfusional Iron Overload

Iron overload is treated with the iron chelator, deferoxamine mesylate (e.g., DesferrixoxamineTM). This agent must be infused slowly, over several hours, and by a subcutaneous or intravenous infusion. Typically patients receive their treatment at home, five days per week.

Reporting - Transfusional Iron Overload

Overview

Documenting and reporting complications of blood transfusion involve many aspects and interrelationships. Policies and procedures will vary from site to site. Where applicable, please find examples of the types of reporting that are required.

Responsibilities of Medical and Nursing Staff

Physicians and nurses attending to patients who experience suspected transfusion complications should perform the following documentation and reporting functions:

• Report suspected reactions immediately to the attending physician and transfusion service.
• Document the patient's signs and symptoms and implicated donor units and send them to the transfusion service, as shown in this example from the National TTI Surveillance System (TTISS):
  - Canadian Transfusion Adverse Event Reporting Form

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

• Maintain records of the complication in the patient’s medical record, including the report of the investigation completed by the transfusion service.

Note: Documentation must be maintained for all transfusions, whether or not complications occur.

Responsibilities of the Transfusion Service

The transfusion service is responsible for several aspects of documenting and reporting transfusion reactions and complications. These include documenting and reporting:

• results of transfusion reaction investigations to the attending physician;
• accidents and errors to the hospital transfusion committee;
• significant complications to the manufacturer and/or distributor;
• significant complications to other authorities as specified by provincial or federal regulations.

The types of reactions that should be reported are provided in the Standards for Blood Safety and below (under Canadian Blood Services).

Responsibilities of Canadian Blood Services

Canadian Blood Services, the blood supplier in all Canadian provinces and territories except Quebec, receives reports of serious adverse reactions from transfusion services and reports them to Health Canada.

IMPORTANT: In Canadian Blood Services’ Circular of Information, review a detailed description about the reporting responsibilities and relationships between itself and transfusion services, including transfusion-transmissible diseases: Section A6. Reporting Serious Adverse Reactions.

Transfusional Iron Overload: Further Reading

Note: Canadian Blood Services offers no endorsement of and assumes no liability for the currency, accuracy, or availability of any information on these sites.

1. Ballas SK. Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol 2001 Jan.;38(1 Suppl 1)30-6. [ Medline ]
2. Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR: Thalassemia Clinical Research Network. Complications of beta-thalassemia major in North America. Blood. 2004 Jul 1; 104(1): 34-9. [Medline]
3. Harmatz P, Butensky E, Quirolo K, Williams R, Ferrell L, Moyer T, et al. Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. Blood 2000 Jul.1;96(1): 76-9.
4. Kushner JP, Porter JP, Olivieri NF. Secondary iron overload. Hematology (Am Soc Hematol Educ Program) 2001 Jan.; 47-61.
5. Olivieri NF. Progression of iron overload in sickle cell disease. Semin Hematol. 2001 Jan.;38(1 Suppl 1):57-62. [ Medline ]