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For further information, see CMDT Part 13-09: Hemolytic Anemias

Key Features

  • Generally classified according to whether the defect is intrinsic or extrinsic to the red blood cell (RBC)

  • Intrinsic

    • Membrane defects

      • Hereditary spherocytosis

      • Hereditary elliptocytosis

      • Paroxysmal nocturnal hemoglobinuria

    • Glycolytic defects

      • Pyruvate kinase deficiency

      • Severe hypophosphatemia

    • Oxidation vulnerability

      • Glucose-6-phosphate dehydrogenase deficiency

      • Methemoglobinemia

    • Hemoglobinopathies

      • Sickle cell syndromes

      • Thalassemia

      • Unstable hemoglobins

      • Methemoglobinemia

  • Extrinsic

    • Immune

      • Autoimmune

      • Lymphoproliferative disease

      • Drug-induced

    • Microangiopathic

      • Thrombotic thrombocytopenic purpura

      • Hemolytic-uremic syndrome

      • Disseminated intravascular coagulation

      • Valve hemolysis

      • Metastatic adenocarcinoma

      • Vasculitis

      • Copper overload

    • Infection

      • Plasmodium

      • Clostridium

      • Borrelia

    • Hypersplenism

    • Burns

Clinical Findings

  • Symptoms of anemia

  • Jaundice, pigment gallstones, cholecystitis in chronic cases

  • Palpable spleen


  • Serum haptoglobin is low but is neither specific nor sensitive

  • Reticulocytosis present unless second disorder (infection, folate deficiency) superimposed on hemolysis

  • Transient hemoglobinemia with intravascular hemolysis

  • Hemoglobinuria when capacity for reabsorption of hemoglobin by renal tubular cells exceeded

  • Urine hemosiderin test positive; indicates prior intravascular hemolysis

  • Hemoglobinemia and methemalbuminemia if severe intravascular hemolysis

  • Indirect bilirubin elevated, total bilirubin elevated to ≤ 4 mg/dL; higher bilirubin elevations may indicate hepatic dysfunction

  • Serum lactate dehydrogenase elevated in microangiopathic hemolysis; may be elevated in other hemolytic anemias


  • See Treatment of specific anemias

  • Folic acid, 1 mg orally once daily

  • Transfusions possible

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