Hemolytic anemia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Differentiating Hemolytic anemia from other Diseases

Characteristic/Parameter	Hemolytic anemia	Sideroblastic anemia	Anemia of chronic disease	Thalassemia	Iron-deficiency anemia	Erythropoietin deficiency	Vitamin B12 or folate deficiency
Etiology	Drug-induced, immune-mediated, non-immune-mediated, infections, rheumatologic disease	Alcoholism, lead poisoning, vitamin B6 deficiency, isoniazid, chloramphenicol	Chronic kidney disease, rheumatologic disease, cancer, HIV, chronic infection; excess release of IL-1 and IL-6	Genetic defect with alpha- or beta-globin production	Petechiae, bleeding, other autoimmune diseases	Petechiae, purpura, ecchymoses	Bleeding, photosensitivity, arthritis, malar rash, discoid rash, renal failure, seizures, psychosis
Mean corpuscular volume	Normocytic (80-100 femtoliter)	Microcytic (<80 femtoliter) or normocytic (80-100 femtoliter)	Normocytic (80-100 femtoliter)	Microcytic (<80 femtoliter)	Low; can be as low as 10000 per microliter	Low; can be less than 10000 per microliter; sudden onset after transfusion	Variable; usually low
Laboratory abnormalities	Indirect hyperbilirubinemia, reticulocytosis, low haptoglobin, elevated LDH	Ringed sideroblasts in bone marrow; low vitamin B6 level, high lead level	Elevated ESR and CRP, elevated hepcidin, low serum iron, low transferrin, elevated ferritin	Abnormal hemoglobin electrophoresis (in beta-thalassemia)	Normal	Normal	Usually normal
Physical exam	Pallor, jaundice	Pallor, weakness	Pallor, weakness	Irritability, growth retardation, jaundice, hepatomegaly, splenomegaly	Idiopathic; can be secondary to chronic lymphocytic leukemia, HIV, viral hepatitis, H. pylori	Exposure to transfused products	Autoimmunity with development of antibodies to DNA
Treatment	Removal of offending agent, steroids, alternative immunosuppression	Removal of offending medication, high-dose vitamin B6 (up to 200mg daily), avoidance of splenectomy, symptomatic transfusion support with iron chelation as needed	Treatment of the underlying cause; erythropoiesis-stimulating agents, supportive red blood cell transfusions	Transfusion support, iron chelation, gene therapy if available	Yes	No; transfusion-related	Possible; drug-induced lupus can be caused by medications like hydralazine or isoniazid
Other associated abnormalities	HELLP syndrome, TTP, CLL	Myelodysplastic syndrome, myeloproliferative neoplasm, iron overload	Inflammatory bowel disease	Extramedullary hematopoiesis	Yes; spontaneous bleeding if platelet count < 10000 per microliter	Yes; spontaneous bleeding if platelet count < 10000 per microliter	Rare