Transfusion Associated GVHD and Post Transfusion Purpura

Transfusion associated graft versus host disease and post transfusion purpura are rare, delayed complications. The first is almost always fatal and entirely preventable. The second is self-limiting but can cause severe bleeding, and is treatable.

Transfusion associated graft versus host disease. Donor T lymphocytes in a cellular component engraft and attack the recipient's tissues, because the recipient cannot reject them. This occurs in immunocompromised patients and, rarely, in immunocompetent recipients when the donor is homozygous for an HLA haplotype shared by the recipient, which is more likely with blood from relatives or in populations with limited HLA diversity.

• Onset 2 to 30 days after transfusion (often 1 to 2 weeks).

• Fever, an erythematous maculopapular rash that starts on the trunk and may become erythroderma with blistering, diarrhoea, abnormal liver function and, unlike graft versus host disease after transplant, bone marrow failure with pancytopenia.

• Mortality is over 90%, usually within weeks, from infection or bleeding.

Post transfusion purpura. Severe thrombocytopenia 5 to 12 days after transfusion of a cellular component, in a patient previously sensitised to a platelet antigen (usually human platelet antigen 1a, in a multiparous woman who lacks the antigen). The recipient's antibody destroys both transfused and the patient's own platelets by a mechanism that is not fully understood.

• Sudden fall in platelet count, often under 10 x 10⁹/L.

• Purpura, mucosal bleeding, haematuria, melaena and, rarely, intracranial haemorrhage.

• Self-limiting over 2 to 4 weeks without treatment.

Special groups. Transfusion associated graft versus host disease: patients with congenital immunodeficiency, Hodgkin lymphoma, purine analogue therapy, transplant, neonates and recipients of blood from relatives. Post transfusion purpura: multiparous women, and patients with previous transfusion.

Transfusion associated graft versus host disease: differential diagnosis. Drug rash, viral exanthem and infection, sepsis, drug induced marrow suppression, engraftment syndrome, transplant related graft versus host disease and disseminated intravascular coagulation. Marrow aplasia and the timing after a non-irradiated cellular component point to the diagnosis.

Post transfusion purpura: differential diagnosis. Immune thrombocytopenia, heparin induced thrombocytopenia, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, drug induced thrombocytopenia, sepsis and consumption from bleeding. A fall in platelet count within 5 to 12 days of a transfusion in a sensitised patient should raise the suspicion.

Initial assessment. Temperature, rash, diarrhoea, liver function, full blood count and film, bleeding sites and platelet count trend, and review of transfusion history, pregnancy history and products given (including irradiation status).

Immediate actions in order (for both, when suspected).

1. Stop any ongoing transfusion of cellular components unless it is life-saving.

2. Assess the patient: airway, breathing, circulation, bleeding and infection, and call senior and haematology help.

3. Keep intravenous access with 0.9% sodium chloride.

4. Recheck identity and the product details, including whether irradiation was specified and delivered.

5. Inform the blood bank and the responsible clinician so that the donor and co-components can be traced.

6. Do not give random donor platelets for post transfusion purpura without specialist advice, because they are usually destroyed.

Investigations: transfusion associated graft versus host disease. Skin biopsy (interface dermatitis with dyskeratosis), liver function, full blood count (pancytopenia), bone marrow examination (hypocellular), and HLA typing with chimerism analysis (donor lymphocytes in recipient blood or tissue) to confirm.

Investigations: post transfusion purpura. Platelet count and film (exclude clumping), coagulation screen, human platelet antigen genotyping of the patient and detection of the platelet specific antibody (anti-human platelet antigen 1a most often), and tests to exclude other causes (heparin antibodies, thrombotic microangiopathy screen).

Transfusion associated graft versus host disease.

• Supportive care: infection prevention and treatment, fluid and nutrition support, transfusion of irradiated, leucodepleted components, and early transfer to a specialist unit.

• Immunosuppression (high dose corticosteroid, antithymocyte globulin, ciclosporin, alemtuzumab) and stem cell transplant have been tried with little success. Outcome is poor.

• Prevention is irradiation (25 Gy) of cellular components for all at risk patients and for any component from a relative.

Post transfusion purpura.

• Intravenous immunoglobulin 1 g/kg daily for 2 days (or 0.4 g/kg daily for 5 days) is first line, with corticosteroid as an adjunct. Plasma exchange for refractory or life-threatening bleeding.

• Platelet transfusion only for life-threatening bleeding, preferably antigen negative platelets (for example human platelet antigen 1a negative) if available, or a large dose of random donor platelets with intravenous immunoglobulin.

• Avoid unnecessary transfusion until recovery.

• Future transfusion: antigen negative cellular components where possible, and the antibody is recorded in the patient's record.

Reporting. Both are serious complications. Report to the transfusion service and haemovigilance system, with donor and recipient investigation.

Prevention.

• Irradiated cellular components for at risk patients, with a clear flag on records and requests.

• Careful records of sensitisation in multiparous women, and antigen negative products for those with a prior episode.

• Leucodepleted products reduce risk in some settings but do not replace irradiation.