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:
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Table 4: Definition of Donors Temporally linked with TRALI or possible TRALI
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| Term | Definition |
| Implicated Donor | A donor is implicated in TRALI if they have demonstrated antibodies to an HLA Class I or II antigen or HNA; the antibody must have specificity for an antigen present on the recipient’s WBCs or there must be a positive reaction noted between donor serum and recipient WBCs, a positive crossmatch. |
| Associated Donor | A donor is associated with a TRALI reaction if a blood component was transfused during the six hours preceding the first clinical manifestation of TRALI. |
The disposition of donors associated with or implicated in a TRALI reaction is provided in the following table:
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Table 5: Disposition of Donors Involved in a Reported TRALI
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| 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 |
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| 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).