7.9 Transfusion Medicine & Late Complications of Transplantation

1. Indications for Transfusion

The governing principle in modern practice is restrictive transfusion, because liberal strategies have repeatedly failed to improve outcomes while increasing harm.

Transfuse one unit at a time and reassess. Ordering two units reflexively is a stewardship failure the exam consistently penalizes.

Platelets: transfuse prophylactically below 10,000 per microliter, below 20,000 with fever or sepsis, below 50,000 before most invasive procedures, and below 100,000 for neurosurgery or ocular surgery. Platelet transfusion is contraindicated in thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia, where it fuels microthrombosis.

Plasma is for bleeding with a documented coagulopathy or for urgent reversal, not for correcting a mildly abnormal INR before a low-risk procedure. Cryoprecipitate supplies fibrinogen and is used when fibrinogen falls below roughly 150 mg/dL in bleeding.

Irradiated products prevent transfusion-associated graft-versus-host disease and are required for hematopoietic cell transplant recipients, patients receiving purine analogues, and directed donations from relatives. Leukoreduction reduces febrile non-hemolytic reactions, cytomegalovirus transmission and alloimmunization, and is standard.

2. Transfusion Reactions

The blueprint lists complications of transfusions and, separately, allergic complications of transfusions including hemolytic reactions, transfusion-related acute lung injury and transfusion-related urticaria and anaphylaxis.

The two most heavily tested discriminations:

TRALI versus TACO. Both cause hypoxemia with bilateral infiltrates within hours of transfusion. TRALI is an inflammatory permeability injury — the patient is often hypotensive, filling pressures and BNP are normal, and treatment is supportive; diuresis is harmful. TACO is hydrostatic — the patient is hypertensive with elevated jugular venous pressure and BNP, and diuresis is the treatment. Blood pressure direction is the fastest bedside clue.

Anaphylaxis and IgA deficiency. An IgA-deficient recipient with anti-IgA antibodies can react anaphylactically to plasma-containing products. Future transfusions require washed red cells or products from IgA-deficient donors. This is the reason to check IgA levels after an unexplained anaphylactic transfusion reaction.

Transfusion-associated graft-versus-host disease is rare, nearly always fatal, and caused by viable donor lymphocytes in a susceptible host. It occurs 1 to 6 weeks after transfusion with fever, rash, diarrhea, hepatitis and pancytopenia — the pancytopenia distinguishes it from transplant-related graft-versus-host disease, in which the graft is the marrow. Irradiation of cellular products prevents it.

3. Iron Overload from Chronic Transfusion

Each unit of red cells contains roughly 200 to 250 mg of iron and the body has no excretory route. Chronically transfused patients — thalassemia, sickle cell disease, myelodysplastic syndrome — accumulate iron in the heart, liver and endocrine organs. Monitor ferritin, quantify with MRI T2* for cardiac and hepatic iron, and use chelation with deferasirox or deferoxamine. Cardiac siderosis is the leading cause of death in transfusion-dependent thalassemia.

4. Late Complications of Hematopoietic Cell Transplantation

The blueprint restricts this topic to late complications only, which tells you the intended scope: the internist inherits these patients years after transplant.

Chronic graft-versus-host disease

The dominant late complication of allogeneic transplantation, typically beginning after day 100 and defined now by clinical features rather than by timing alone.

Treatment is systemic corticosteroids with steroid-sparing agents. The consequence for the internist is functional asplenia and profound, prolonged immunodeficiency, since chronic graft-versus-host disease and its therapy suppress immune reconstitution for years.

Infection risk after transplantation

Patients with chronic graft-versus-host disease require antimicrobial prophylaxis against encapsulated organisms and Pneumocystis, and remain at risk for varicella-zoster reactivation, cytomegalovirus and invasive fungal infection.

Revaccination is mandatory, because transplantation erases pre-existing immunity. The childhood series is repeated on a defined schedule beginning several months after transplant. Live vaccines are deferred, typically to at least two years and only in the absence of active graft-versus-host disease and immunosuppression.

Other late complications

• Secondary malignancy — therapy-related myelodysplastic syndrome and acute leukemia, and an elevated lifetime risk of solid tumors, particularly skin cancer (rigorous photoprotection and skin surveillance are warranted) and cancers of the oral cavity and thyroid
• Endocrine — hypothyroidism, hypogonadism, infertility, growth hormone deficiency, adrenal insufficiency from prolonged steroid exposure
• Bone — osteoporosis and osteonecrosis
• Cataracts, particularly after total body irradiation
• Cardiovascular disease, accelerated by anthracycline exposure, irradiation and metabolic syndrome
• Iron overload from cumulative transfusion

Post-transplant lymphoproliferative disorder is Epstein-Barr virus-driven and presents with lymphadenopathy, fever and organ dysfunction; management begins with reduction of immunosuppression and rituximab.

5. Hematologic Complications of HIV Infection

A separately named blueprint subsection appearing under both Hematology and Infectious Disease.

• Anemia is the most common hematologic abnormality and is multifactorial: anemia of chronic disease, direct marrow suppression, opportunistic infection, drug effect and nutritional deficiency.
• Parvovirus B19 causes pure red cell aplasia in advanced HIV — profound anemia with a near-zero reticulocyte count and giant pronormoblasts on marrow examination. It responds to intravenous immunoglobulin, and untreated it persists because the host cannot clear the virus.
• Immune thrombocytopenia is common and frequently improves with antiretroviral therapy alone, which is often the correct answer rather than immunosuppression.
• Neutropenia from disease, opportunistic infection or drugs including zidovudine, ganciclovir and trimethoprim-sulfamethoxazole.
• Thrombotic thrombocytopenic purpura occurs at increased frequency.
• Malignancy — HIV-associated lymphoma, including primary central nervous system lymphoma and primary effusion lymphoma.

Effective antiretroviral therapy improves most HIV-associated cytopenias, which is the unifying management principle across this subsection.