Hemolytic anemia differential diagnosis

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

Overview

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 Loss of iron from gastrointestinal blood loss or menstrual blood loss Chronic kidney disease or other renal dysfunction 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) Microcytic (<80 femtoliter) Normocytic (80-100 femtoliter) 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) Low serum iron, elevated transferrin, low transferrin saturation, low ferritin Low erythropoietin level Usually normal
Physical exam Pallor, jaundice Pallor, weakness Pallor, weakness Irritability, growth retardation, jaundice, hepatomegaly, splenomegaly Pallor, weakness, positive occult blood testing (if GI bleeding) Pallor, weakness, signs of chronic kidney disease 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 Intravenous or oral iron supplementation Epoetin alfa 50-100 units/kg 3 times weekly, darbepoietin 0.45 mcg/kg weekly or 0.75 mcg/kg every 2 weeks 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 Chronic blood loss Dialysis dependence, myelodysplastic syndrome Rare

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