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)