Transfusion medicine

• Transfusion related acute lung injury (TRALI) is an adverse outcome of transfusion in which acute respiratory distress occurs within 6 hours of a transfusion
• This is typically an antibody mediated process in which antibodies in the transfused product or less commonly in the recipient attract neutrophils to the pulmonary vasculature

• Women who have been pregnant have a higher likelihood of developing HLA and HNA antibodies due to alloimmunization from the fetus
• Most significant in plasma rich products such as fresh frozen plasma and apheresis platelets
• Initial efforts to limit products from female donors → use of male only plasma in U.K. and U.S. → reduced rate of TRALI dramatically
• Screening donors for anti-HLA
• References: Transfus Med 2008;18:348, Vox Sang 2008;95:313, Hematology Am Soc Hematol Educ Program 2018;2018:585

• Defer donors confirmed to be implicated in TRALI
• Use only male plasma to avoid risk of anti-HLA antibodies formed in women during pregnancy
• Screen female donors of apheresis platelets for HLA antibodies, indefinitely defer those with antibodies
• References: Hematology Am Soc Hematol Educ Program 2018;2018:585, Vox Sang 2017;112:694, AABB: TRALI Risk Mitigation for Plasma and Whole Blood for Allogeneic Transfusion [Accessed 8 January 2020], Transfusion 2010;50:1312, AABB: Standards for Blood Banks and Transfusion Services, 31st Edition, 2018, Fung: Technical Manual, 19th Edition, 2017

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• 4 month old girl and 78 year old woman, transfusions between mothers and daughters (Am J Clin Pathol 2004;121:590)
• 2 cases in children (Transfus Med 2006;16:343)
• 28 and 31 year old men with thalassemia (Mediterr J Hematol Infect Dis 2017;9:e2017060)
• 67 year old man with transfusion for iron deficiency anemia (CMAJ 2007;177:149), recurrence 2 years later (Transfus Med 2007;17:192)
• 77 year old woman with common variable immune deficiency (Transfusion 2014;54:3088)
• Patient with hematologic malignancy and neutropenia associated pneumonitis (Transfusion 2003;43:1683)

• Stop the transfusion
• Report the transfusion to transfusion medicine service to start the investigation
• Supportive management only
• Mechanical ventilation may be needed in severe cases
• Most patients improve within 48 - 96 hours
• Mortality is 5 - 10%
• Indefinite deferral of blood donor to prevent future cases
• Deaths from TRALI: during fiscal years 2012 - 2016, the combined TRALI and possible TRALI cases caused the highest number of reported fatalities, 64 out of 186 total fatalities (34%) (FDA: Transfusion Related Acute Lung Injury (TRALI) [Accessed 8 January 2020])

• Assessment: John Doe is a 75 year old man who developed respiratory distress 2 hours after a packed red blood cell (pRBC) transfusion. He had normal ejection fraction, no elevation in brain natriuretic peptide (BNP) and treatment with diuretics did not resolve his respiratory distress. The blood supplier was notified and performed testing of donor sample. Testing of the donor sample identified anti-HLA DR11, DR13 and DR52. Patient had matching cognate antigens - HLA type DR11, DR13 and DR52.
• Plan: The patient presentation and laboratory workup are consistent with a diagnosis of transfusion related acute lung injury (TRALI).

• Transfusion associated circulatory overload:
  • Fluid overload → increased pulmonary capillary pressure → cardiogenic edema = congestive heart failure
  • Patient often has predisposition to congestive heart failure
  • Hypertension rather than the hypotension typically seen in TRALI
  • Elevated brain natriuretic peptide (BNP), e.g. post to pretransfusion ratio of BNP ≥ 1.5 (indicates stretched ventricular muscle due to volume overload)
  • Transudative rather than exudative alveolar edema
  • All blood components have been implicated, volume issue, no particular product is more commonly associated
• Transfusion associated dyspnea:
  • Diagnosis of exclusion that does not meet criteria for TRALI or transfusion associated circulatory overload
  • No specific underlying pathophysiology has been identified

One key feature seen in transfusion related acute lung injury but not in transfusion associated circulatory overload is

1. Decreased oxygen saturation
2. Hypotension
3. More likely to have underlying cardiac dysfunction
4. New pulmonary infiltrates
5. Response to diuretics

B. Hypotension is often seen in transfusion related acute lung injury, as opposed to hypertension seen in transfusion associated circulatory overload, as a result of expansion of intravascular fluid volume, making choice B the correct response. The answer choices of new pulmonary infiltrates and decreased oxygen saturation are seen in both. Response to diuretics and pre-existing, underlying cardiac dysfunction are more commonly seen in transfusion associated circulatory overload.

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Reference: Transfusion related acute lung injury (TRALI)

A 55 year old woman with acute myeloid leukemia, status postallogeneic bone marrow transplant with severe neutropenia and unresponsive fungal infection is receiving granulocytes. She develops severe respiratory distress shortly after the transfusion is completed, necessitating mechanical ventilation. Her fluid balance is neutral and she has no pre-existing cardiac dysfunction. What laboratory testing would help confirm a diagnosis of inverse transfusion related acute lung injury?

1. Anti-HLA / HNA antibodies in the donor that match antigens in the recipient
2. Anti-HLA / HNA antibodies in the recipient that match antigens in the donor
3. Elevated brain natriuretic peptide (BNP)
4. Pleural fluid with protein content < 2.5 g/dL and fluid protein to serum protein ratio of < 0.5 and cholesterol content of < 45 mg/dL
5. Short lived, sudden increase in neutrophils in complete blood count

B. Anti-HLA / HNA antibodies in the recipient that match antigens in the donor. Inverse transfusion related acute lung injury refers to the recipient having antibodies against antigens in the donor, so choice B. Elevated brain natriuretic peptide and transudative pulmonary fluid are seen in transfusion associated circulatory overload. Choice A describes traditional transfusion related acute lung injury occurring when antibodies in the donor match cognate antigens in the recipient. Choice E is incorrect because transfusion related acute lung injury may feature a sudden, short lived decrease rather than increase in neutrophils in a complete blood count.

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Reference: Transfusion related acute lung injury (TRALI)