Etiology


By RBC pathology

  • Intrinsic hemolytic anemia
    • Increased destruction of RBCs due to a defect within the RBC
  • Extrinsic hemolytic anemia
    • Abnormal breakdown of normal RBCs

By location of RBC breakdown

  • Intravascular hemolytic anemia
    • Increased destruction of RBCs within the blood vessels
  • Extravascular hemolytic anemia
    • Increased destruction of RBCs by the reticuloendothelial system (primarily the spleen)

Diagnostics


  • Indirect (unconjugated) bilirubin
    • Hemolysis → Hb release → heme catabolized to indirect bilirubin
    • More prominent in extravascular hemolysis
      • Heme needs to be catabolized to indirect bilirubin. Macrophages within the reticuloendothelial system (80% in the spleen and 20% in the bone marrow) are predominantly responsible for heme breakdown.
  • Hemoglobinuria, Hemosiderinuria
    • More prominent in intravascular hemolysis
      • Free Hb can’t be catabolized, so they are excreted in urine.
  • Lactate dehydrogenase (LDH)
    • Nonspecific parameter; indicates increased cellular breakdown
    • More prominent in intravascular hemolysis
  • Peripheral blood smear
    • Intravascular hemolysis
      • ↑ Reticulocytes
      • Heinz bodies and bite cells in G6PD deficiency
      • Schistocytes in MAHA or macroangiopathic hemolysis
      • Intracellular organisms (e.g., in malaria , babesiosis , bartonellosis )
    • Extravascular hemolysis
      • ↑ Reticulocytes
      • Spherocytes in hereditary spherocytosis and immune-mediated hemolysis (e.g., warm AIHA, hemolytic transfusion reactions)
        • Spherocytes are typically found in warm AIHA due to splenic macrophages partially ingesting IgG-coated RBC membranes. A positive DAT and negative family history can distinguish warm AIHA from hereditary spherocytosis.
      • RBC agglutination in cold agglutinin disease (CAD)
      • Sickle cells in sickle cell disease
      • Target cells in HbC disease, Asplenia, Liver disease, Thalassemia
        • A type of pathologic red blood cell with a bullseye appearance due to an overabundance of membrane.
        • HALT,” said the hunter to his target
      • Teardrop cells in thalassemia
      • Hb crystals within RBCs in hemoglobin C disease
      • Smudge cells (Gumprecht shadows) in chronic lymphocytic leukemia (CLL)