Transfusion medicine

Transfusion reactions & complications

Transfusion associated graft versus host disease



Last author update: 25 July 2022
Last staff update: 25 July 2022

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PubMed Search: Transfusion associated graft versus host disease

Deyze Badarane, M.D., M.P.H., C.P.H.
Kyle Annen, D.O.
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Cite this page: Badarane D, Annen K. Transfusion associated graft versus host disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedgvhd.html. Accessed February 8th, 2023.
Definition / general
Essential features
  • Highly preventable
  • Most common clinical manifestations include fever (7 - 10 days after transfusion), pancytopenia, maculopapular rash on the face and trunk that spreads to extremities, diarrhea, abdominal pain, mucositis, hepatitis, jaundice and marrow aplasia (Arch Pathol Lab Med 2018;142:662)
Terminology
  • Transfusion associated graft versus host disease (TA-GVHD)
Pathophysiology
  • Active T lymphocytes (CD4, CD8 and NK cells) are transfused from a nonidentical donor (the graft) with human leukocyte antigen (HLA) incompatibility and recognize the transfused recipient (the host) as foreign, initiating an immune attack that causes tissue damage in the transfused recipient (Arch Pathol Lab Med 2018;142:662)
  • Lymphocytes from the recipient cannot counterattack (immunosuppressed recipient) or do not recognize the graft (donor) as foreign (immunocompetent HLA heterozygous recipient from an HLA homozygous donor, i.e., HLA one way compatibility)
    • Recipient fails to respond to neutralize the donor; viable, transfused T lymphocytes attack and lead to GVHD
Clinical features
  • National Health and Safety Network (NHSN) established the criteria diagnostic of TA-GVHD based on a combination of clinical and histologic findings that occur between 2 days and 6 weeks after a transfusion (Blood 2015;126:406)
  • All cellular blood products and fresh plasma are implicated; products that have been frozen do not pose a risk due to the destruction of donor lymphocytes by freezing
  • Incidence of TA-GVHD is lower than that of bone marrow transplant related GVHD
Symptoms
  • Clinical manifestations affect the skin, GI tract, liver and bone marrow; severe neutropenia leading to untreatable infection is the primary cause of death in TA-GVHD (Am J Clin Pathol 2000;113:732)
    • Constitutional: fever
    • Skin: can range from erythematous maculopapular rash to toxic epidermal necrolysis
    • Liver: hepatomegaly, jaundice
    • GI: abdominal pain, diarrhea, vomiting, anorexia
Laboratory
  • Complete blood count (CBC) shows pancytopenia
  • Peripheral blood smear confirms pancytopenia with a low reticulocyte response
  • Metabolic panel will show abnormal liver and kidney function
  • Bone marrow: aplasia, pancytopenia, lymphoid and histiocytic infiltrates
  • Liver or skin biopsy (rare) (Hematol Rep 2018;10:7724)
  • Donor lymphocyte DNA (polymerase chain reaction [PCR] based HLA typing)
Prevention
  • Blood products, such as whole blood, red blood cells, platelets, granulocytes and plasma that have not been frozen (e.g., liquid plasma), can contain viable T lymphocytes and cause TA-GVHD
  • Gamma irradiation of cellular blood products
    • T cells are sensitive to high doses of radiation
    • Cellular blood products must be irradiated with a minimum of 25 Gy to the center of the unit and 15 Gy to the periphery
  • Pathogen reduction technology: process uses a psoralen compound and UV light to crosslink DNA and RNA in the target pathogens (viruses / bacteria) but also crosslinks the DNA of any T lymphocytes in the product, which provides comparable results as irradiation (Vox Sang 2017;112:607)
  • Leukocyte reduction does not prevent TA-GVHD but does reduce the risk, due to an overall lower dose of residual T lymphocytes in the product
Risk factors / indications for irradiation
  • Selected immunosuppressed patients (Bone Marrow Transplant 2004;33:1, Hematol Rep 2018;10:7724):
    • Congenital T cell deficiencies
    • Intrauterine transfusion or neonatal exchange transfusion recipients
    • Marrow transplant recipient or candidate
    • Taking purine analogs such as fludarabine, anti-CD52 medications (alemtuzumab) or other drugs that affect T cells
    • Hodgkin disease, leukemia or lymphoma patients
    • Requiring granulocyte transfusions
    • Irradiation is not required for patients with HIV / AIDS
  • Selected immunocompetent patients:
    • Those receiving blood transfusion from a first degree relative (in practice, products from any relative should be irradiated)
    • Partial HLA matched units
    • Neonates who have received intrauterine transfusions
    • Healthy newborns do not need irradiation, however, some facilities may choose to irradiate up to a certain age to avoid the possibility of an immunodeficiency that has not manifested (e.g., DiGeorge syndrome, congenital neutropenia syndromes, such as all patients < 1 year of age)
Case reports
  • 50 year old immunocompetent woman who received whole blood transfusion from an unrelated donor (Indian J Hematol Blood Transfus 2010;26:92)
  • 53 year old man with TA-GVHD following hepatectomy for hepatocellular carcinoma (Kurume Med J 1993;40:193)
  • 61 year old woman with chronic lymphocytic leukemia (CLL) was treated with fludarabine followed by combination chemotherapy / radioimmunotherapy and peripheral blood progenitor cell (PBPC) rescue (Transfusion 2002;42:1567)
Treatment
Sample assessment & plan
  • Assessment: Patient X is a 63 year old man with a 60 pack year tobacco history, diabetes mellitus and hypertension. He was admitted to the hospital with acute, severe left chest pain and was found to have coronary artery disease. He underwent coronary artery bypass graft surgery, during which he received 4 units of nonirradiated packed red blood cells. 2 weeks after the procedure, he presented in the emergency department with a fever (104 °F), nausea, vomiting, erythematous rash on his trunk / extremities and abdominal pain. Laboratory tests revealed abnormal liver and kidney function, pancytopenia, bone marrow aplasia and increased levels of lactate dehydrogenase (LDH), amylase and lipase. HLA typing was performed on the patient and on the red blood cell transfusion donors, revealing that the donor shared an HLA haplotype. The skin biopsy showed vacuolar dermatitis with a lymphocytic infiltrate.
  • Impression: Transfusion associated graft versus host disease
  • Plan:
    • Supportive care and steroids.
    • Evaluation by hematology / oncology for bone marrow transplant may be considered, however, this disease process has an extremely poor outcome.
    • Should have a discussion regarding prognosis with the patient.
    • Palliative care consultation may be appropriate based on the patient's wishes.
Differential diagnosis
Board review style question #1
A 68 year old man with lymphoma presents to the hospital to undergo cardiac surgery with low levels of platelets. The blood bank director recommended transfusion of irradiated platelets before surgery. Which is the correct explanation regarding the blood bank director's recommendation?

  1. Irradiation of platelets and red blood cells prevents acute hemolytic transfusion reactions (AHTR)
  2. Irradiation of platelets and red blood cells prevents febrile nonhemolytic transfusion reactions (FNHTR)
  3. Irradiation of platelets and red blood cells prevents transfusion associated graft versus host disease (TA-GVHD)
  4. Irradiation of platelets and red blood cells prevents transfusion related acute lung injury (TRALI)
  5. Irradiation of platelets and red blood cells prevents transfusion associated circulatory overload (TACO)
Board review style answer #1
C. Irradiation of platelets and red blood cells prevents transfusion associated graft versus host disease (TA-GVHD), especially in a patient with hematological malignancy such as this one.

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Reference: Transfusion associated graft versus host disease
Board review style question #2
A 4 month old boy was brought to the emergency department by his mother for fever, diarrhea, vomiting, abdominal pain and anorexia that started 3 days ago. On physical examination, there is a diffuse maculopapular skin rash. His significant previous medical history includes a preterm birth and having received a blood transfusion 8 days ago. Laboratory findings include pancytopenia and elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Which of the following is the most likely diagnosis in this patient?

  1. Cytomegalovirus colitis
  2. Drug reaction
  3. Henoch-Schönlein purpura
  4. Hepatitis B
  5. Transfusion associated graft host disease (TA-GVHD)
Board review style answer #2
E. Transfusion associated graft host disease (TA-GVHD)

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