HEMOLYSIS

I. Conditions which result in significant intravascular hemolysis

  1. Paroxysmal nocturnal hemoglobinuria (PNH)
    1. An acquired clonal disorder of hemopoietic stem cells, involving inability of complement proteins to attach to the erythrocyte, rendering them extremely sensitive to complement-mediated lysis
    2. Results in chronic intravascular hemolysis
    3. Characterized by episodes of severe intravascular hemolysis, with hemoglobinuria (sometimes to the point of the urine turning black), dysphagia, abdominal pain, erectile dysfunction, thrombosis, disabling fatigue, and in severe cases, renal failure
    4. Paroxysms can be triggered by infection, drugs, or trauma; some seem to occur spontaneously; usually last 3-7d
  2. Sickle Cell Disease
  3. Thalassemias
  4. Hereditary spherocytosis
  5. Thrombotic Thrombocytopenic Purpura and other microangiopathic hemolytic anemias
  6. Pyruvate kinase deficiency
  7. G6PD
  8. ABO mismatch Transfusion reactions
  9. Paroxysmal cold hemoglobinuria
  10. Severe idiopathic autoimmune hemolytic anemia
  11. Infection-induced anemia
  12. Malaria
  13. Cardiopulmonary bypass
  14. Mechanical heart valve-induced anemia
  15. Chemical-induced anemias

II. Diagnosis of hemolysis

  1. Serum LDH usually elevated in proportion to severity of hemolysis

III. Physiologic sequelae of intravascular hemolysis

  1. Nitric oxide has a paracrine function; secreted by endothelium and acting to relax vascular smooth muscle
  2. Hemoglobin reacts rapidly and irreversibly with nitric oxide, depleting intravascular nitric oxide
  3. Natural mechanisms scavenge the small amount of intravascular free hemoglobin produced by physiologic hemolysis
  4. Pathologic hemolysis overwhelms these mechanisms, resulting in accumulation of cell-free intravascular hemoglobin and reducing nitric oxide concentrations

IV. Clinical manifestations of hemolysis

  1. Smooth muscle dystonias (due to nitric oxide deficiency), including:
    1. Arterial hypertension (due to vasoconstriction)
    2. Gastrointestinal contractions (resulting in abdominal pain and dysphagia)
    3. Erectile dysfunction
  2. Abnormal thrombosis (due to nitric oxide deficiency increasing platelet activation)
  3.  

(Sources include JAMA 293:1653, 2005)