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Transfusion medicine

Tranfusion reaction

Transfusion associated graft versus host disease (Ta-GVHD)


Reviewer: Huy Phu Pham, M.D. (see Reviewers page)
Revised: 2 November 2011, last major update September 2011
Copyright: (c) 2007-2011, PathologyOutlines.com, Inc.

General
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● Rare, but almost universally fatal complication of transfusion
● Goal: identify patients at risk for Ta-GVHD so that appropriate products can be given

Pathophysiology
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● Similar to acute GVHD after hematopoietic progenitor cell transplantation
● Viable donor CD8+ T cells proliferate and attack recipientís bone marrow cells and possibly other organs (Osaka City Med J 1999;45:37) and recipientís immune system does not attack these donor T cells
● May be less likely in blood stored 4+ days due to WBC inactivation (Br J Haematol 2000;111:146)
● Appears to have been reduced after universal leukoreduction in UK (Transfusion 2007;47:1455)
● Recipient may have normal immunity if homozygous for a HLA haplotype and donor is heterozygous with one shared haplotype, which causes donor cells to see recipient cells as foreign, but recipient cells donít see donor cells as foreign (high risk if directed donations from first or second degree relatives); also risk factor in rural areas where gamma radiation is not possible (Transfusion 2007;47:1405, Indian Pediatr 2004;41:1260)

Clinical manifestation
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● Usually occurs at ~4 weeks after transfusion
● Fever (day 28), skin rash (day 30), diarrhea, abnormal liver function tests
● Death (day 51), usually due to sepsis because of leukopenia and pancytopenia

Diagnosis
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● Diagnosis based on clinical findings and laboratory and biopsy results
● Easily confused with severe viral illness or adverse reaction in severely ill patients if Ta-GVHD is not suspected - considered to be underdiagnosed and underreported
● Confirm diagnosis by finding donor lymphocytes or DNA in patientís peripheral blood or tissue biopsy, with the appropriate clinical symptoms

Treatment
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● Most treatment options are unsuccessful and are only palliative
● Steroids, antithymocyte globulin and cyclosporin
● Nafmostat mesilate gives transient improvement
● Almost universally fatal Ė usually due to infections

Prevention
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● Identify patients at risk, and transfuse them ONLY with irradiated blood products
● Leukoreduction does NOT prevent Ta-GVHD

Indications for irradiating blood products for Ta-GVHD prevention:
● Absolute:
       ● Chemotherapy with purine analogs, Campath (anti-CD52) or other drugs that affect T cells
       ● Congenital cellular immunodeficiency (severe combined immunodeficiency, DiGeorge syndrome) Ė suspected or known
       ● Hematopoietic progenitor cell transplantation (both allo- and autologous)
       ● Granulocyte transfusion
       ● Hodgkin lymphoma
       ● Neonates who have received intrauterine transfusions
       ● Transfusions from blood relatives
       ● HLA-matched or partially HLA-matched products
● Relative:
       ● Neonates or infants < 1200g
       ● Neonate exchange transfusions
       ● Non-Hodgkin lymphoma/leukemia (Vox Sang 2002;83:279)
       ● High dose chemotherapy, radiation therapy or aggressive immunotherapy due to leukemia or solid tumor
       ● Aplastic anemia
● Controversial:
       ● Solid organ transplants, large volume or exchange transfusions in infant who did not receive intrauterine transfusion
       ● Absolute lymphopenia
● Probably NOT required:
       ● HIV infection
       ● Healthy newborn or term infants
       ● Hemophilia, humoral immunodeficiency (common variable immunodeficiency)
       ● Small volume transfusions in term infant who did not receive intrauterine transfusion
       ● Elderly, immunosuppression other than purine analogs, pregnancy, red cell disorders (hemoglobin, membrane or metabolic)

Case reports
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● Fatal case caused by blood from unrelated HLA homozygous donor #1 (Am J Clin Pathol 2000;113:732, #2: Transfusion 2006;46:885)
● 65 year old man who received blood from first degree relatives (J Natl Med Assoc 2005;97:418)

End of Transfusion Medicine > Tranfusion reaction > Transfusion associated graft versus host disease (Ta-GVHD)


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