Discuss the patho-physiology of transfusion related lung injury (TRALI). Describe how you would diagnose and manage this condition and discuss the strategies for preventing TRALI.
Pathogenesis
- Donor derived leucocyte antibodies
- HLA (class I and II) and HNA (human neutrophil antigen)
- Multiparous female donors / male donors with previous exposure through transfusion
- Binding of leucocyte antibodies in the donation leads to activation of leukocytes in the patient
- The reason that the lungs are targeted is not certain – may be that this is the first capillary bed that transfused leukocytes pass through.
- Not all transfusions containing HLA/HNA antibodies cause TRALI (two hit hypothesis)
- Less commonly, antibody is in the patient and donor derived lymphocytes are activated
- Antibodies react with patient leucocytes leading to complement mediated leucocyte activation
- Release of proteolytic enzymes and toxic oxygen metabolites damages pulmonary capillary endothelium
Clinical features
- Bilateral perihilar infiltrates and hypoxia within 6 hours of transfusion
- No other readily identifiable cause
- Definition of ALI PaO2/FiO2 (arterial PO2 / fraction of inspired oxygen) ratio <300mmHg / ARDS <200mmHg
Predisposing factors
- Haematological malignancy
- Elective surgery (cardiac)
Blood components
- Plasma rich – Platelets / FFP / Whole blood / Cryoprecipitate
- Red cells (less risk than plasma rich components)
- IVIg (single case)
Management
- Prompt respiratory support
- No evidence for steroids or diuretics
- Mortality 5%
Investigation of cases
- Clinical diagnosis – refer to hospital’s blood bank initially
- Then referred to designated NBS consultant and SHOT
- Collect clinical details
- Identify donors to be investigated / temporarily suspended
- Units in the 6 hours prior to TRALI initially females with previous pregnancies (and males with previous transfusions)
- Temporarily suspend from donating
- Recall other components from the same donation
- Samples from patient to national granulocyte immunology laboratory
- HLA and HNA antibodies in donors and patient (costs £300 for each)
- Screen archived samples for HLA / HNA antibodies
- Fresh donor samples required to confirm results and determine HLA and HNA antigens
- May need follow up samples from patient to determine whether a weak antibody represents an immune antibody or a transferred antibody
Reporting
- Highly likely if donor has specific leukocyte allo-antibodies and the patient is positive for the antigen
- Likely if donor serum has non-specific antibodies which are positive when cross-matched with the patient
- Possible if patient has leukocyte antibody which corresponds to leukocyte antigen in the donors (less likely mechanism since leukodepletion) or donor has leukocyte antibodies but patient is negative or weak positive pan-reactive leucocyte antibodies
- Unlikely if no leukocyte antibodies in either patient or donor
- Antibodies not detected in about 10%
Prevention
- Implicated donors should not be used again
- Exclude multiparous women as donors of whole blood / FFP / Platelet concentrates (apheresis)
- Screen multiparous women for antibodies
- Pool plasma which dilutes antibodies
- Remove plasma from cellular blood components
- Leucocyte depletion will prevent the small number