What underlying conditions predispose someone to blood transfusions, such as paraneoplastic syndromes?

Underlying Conditions Predisposing to Blood Transfusions

Multiple hematologic, oncologic, inflammatory, and congenital disorders predispose patients to requiring blood transfusions, with the most clinically significant being myelodysplastic syndromes, thalassemia, sickle cell disease, chronic kidney disease, inflammatory bowel disease, and various paraneoplastic syndromes associated with malignancy.

Hematologic Malignancies and Bone Marrow Disorders

Myelodysplastic Syndromes (MDS)

• MDS is characterized by ineffective hematopoiesis where bone marrow appears cellular but produces insufficient mature blood cells, leading to chronic progressive cytopenia requiring frequent transfusions 1
• Approximately 82% of MDS patients require transfusions during the disease course, with median requirements of 11.1 units of packed red blood cells per patient per year 2
• The underlying pathophysiology involves clonal abnormalities originating in pluripotent hematopoietic stem cells, resulting in premature cell death (apoptosis) in the bone marrow before cells can fully mature 1
• MDS patients frequently develop transfusion-related complications, with 80% requiring specially processed blood products and 94% of all red blood cell transfusions being complicated 2
• 25-40% of MDS patients progress to acute leukemia, which dramatically increases transfusion requirements to a median of 24 units of packed red blood cells during the acute leukemia phase 1, 2

Thalassemia

• Transfusion-dependent thalassemia patients accumulate approximately 200-250 mg of elemental iron per unit of packed red blood cells, with no physiological mechanism for iron excretion 3, 4
• Cardiac iron loading from chronic transfusions is the leading cause of death in transfusion-dependent thalassemia, accounting for approximately 70% of deaths 3
• Non-transfusion-dependent thalassemia patients develop iron overload primarily through increased gastrointestinal iron absorption due to ineffective erythropoiesis 3
• Before chelation therapy became available, patients with transfused but unchelated β-thalassemia typically died by age 10 from cardiac complications 3

Congenital and Acquired Blood Disorders

Hemoglobinopathies and Coagulopathies

• Sickle cell anemia requires transfusion during acute crisis episodes and for prevention of stroke in high-risk patients 5, 6
• Factor VIII deficiency (hemophilia A) predisposes to bleeding complications requiring transfusion support 6
• Idiopathic thrombocytopenic purpura causes severe thrombocytopenia that may require platelet transfusions 6

Bone Marrow Failure Syndromes

• Aplastic anemia results in pancytopenia requiring chronic transfusion support for both red blood cells and platelets 1
• Pure red cell aplasia can occur as a medication side effect (particularly with azathioprine) or from parvovirus B19 infection in immunocompromised patients 6

Chronic Inflammatory and Autoimmune Conditions

Inflammatory Bowel Disease (IBD)

• Anemia occurs in IBD patients through multiple mechanisms: chronic blood loss, iron deficiency from malabsorption, anemia of chronic disease from inflammatory cytokines, and medication-induced bone marrow suppression 6
• Azathioprine and 6-mercaptopurine used for IBD treatment cause bone marrow toxicity in 5-25% of patients, including pancytopenia, autoimmune hemolytic anemia, leukopenia, and pure red cell aplasia 6
• Blood transfusion may be considered when hemoglobin falls below 7 g/dL or above this threshold if symptoms or particular risk factors are present 6

Chronic Kidney Disease

• Anemia in CKD results from decreased erythropoietin production by failing kidneys, requiring either erythropoiesis-stimulating agents or transfusion support 4, 6
• Transfusion is typically initiated when hemoglobin is less than 10 g/dL in dialysis patients, though restrictive strategies targeting 7-8 g/dL are recommended for most stable patients 4, 7
• Post-transplant anemia (PTA) occurs in kidney transplant recipients due to immunosuppressive medications (particularly sirolimus, cyclosporine, and tacrolimus), ACE inhibitors/ARBs, antiviral medications, and antimicrobials 6

Malignancy-Associated Conditions

Direct Tumor Effects

• Bone marrow infiltration by leukemia, lymphoma, or metastatic solid tumors directly suppresses normal hematopoiesis 6, 8
• Choroidal lymphoma and leukemia can present with anemia alongside other hematologic abnormalities including thrombocytopenia and leukopenia 6

Paraneoplastic Syndromes

• Paraneoplastic syndromes arise from tumor secretion of hormones, peptides, or cytokines, or from immune cross-reactivity between malignant and normal tissues, affecting multiple organ systems including the hematologic system 8
• Hemophagocytic syndrome (HPS) is a rare paraneoplastic cause of post-transplant anemia where activated macrophages infiltrate bone marrow and phagocytose red blood cells, often triggered by viral infections (CMV, Epstein-Barr virus) or lymphoproliferative disease 6
• Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a paraneoplastic syndrome associated with non-ocular tumors that can cause systemic manifestations 6
• Paraneoplastic inflammation in MDS presents with autoimmune manifestations in approximately 10% of patients, causing increased morbidity and mortality 9

Chemotherapy-Induced Myelosuppression

• Myelosuppressive chemotherapy causes anemia requiring transfusion support, particularly in patients with breast cancer, non-small cell lung cancer, head and neck cancers, lymphoid malignancies, and cervical cancers 4
• Transfusion is indicated only when anemia is due to concomitant myelosuppressive chemotherapy with a minimum of two additional months of planned treatment 4

Infection-Related Causes

Viral Infections

• Cytomegalovirus (CMV) infection causes anemia in transplant recipients through direct bone marrow suppression 6
• Parvovirus B19 infection causes pure red cell aplasia in immunocompromised patients, including transplant recipients 6
• Hemolytic uremic syndrome (HUS) may occur de novo or recur after transplantation, associated with CMV, influenza A, or immunosuppressive medications (cyclosporine, tacrolimus, OKT3) 6

Medication-Induced Causes

Immunosuppressive Agents

• Sirolimus demonstrates dose-dependent association with anemia by interfering with intracellular signaling pathways activated by erythropoietin receptor binding 6
• Calcineurin inhibitors (cyclosporine, tacrolimus) cause microangiopathy and hemolysis 6
• OKT3 is associated with hemolytic uremic syndrome and microangiopathy 6

Anticoagulants and Antiplatelet Agents

• Chronic use of warfarin, clopidogrel, and aspirin increases bleeding risk, predisposing to transfusion requirements during surgical procedures 6
• These medications should be discontinued before elective surgery with sufficient time for anticoagulation effects to dissipate 6

Antiviral and Antimicrobial Medications

• Ganciclovir and trimethoprim-sulfamethoxazole commonly cause anemia in transplant recipients and immunocompromised patients 6

ACE Inhibitors and Angiotensin Receptor Blockers

• ACE inhibitors and ARBs are associated with post-transplant anemia through multiple mechanisms: inhibition of endogenous erythropoietin production, inhibition of angiotensin II-mediated stimulation of red blood cell precursors, and generation of erythropoiesis-inhibiting proteins 6
• A significant curvilinear dose-response relationship exists between ACE inhibitor dose and hematocrit 6

Liver Disease

• Chronic liver disease causes anemia through multiple mechanisms: decreased thrombopoietin production, portal hypertension with hypersplenism and sequestration, coagulopathy from decreased clotting factor synthesis, and gastrointestinal bleeding from varices 6

Critical Pitfalls to Avoid

• Do not assume transfusion alone corrects underlying iron deficiency—the iron from transfused red cells must first be recycled through the reticuloendothelial system over the 100-110 day lifespan of transfused cells 7
• Avoid overlooking coexisting paraneoplastic inflammatory disease in MDS patients, as these conditions are often mistakenly diagnosed as idiopathic autoimmune disorders 9
• Do not continue escalating erythropoiesis-stimulating agent doses in non-responsive patients over 12 weeks, as this increases risks without improving outcomes 4
• Always exclude other treatable causes of anemia (vitamin B12/folate deficiency, infections, malignancies, medication side effects) before attributing anemia solely to chronic disease 6
• Recognize that blood transfusions do not correct underlying pathology and have no lasting effect—they are only a transient intervention 6