Drug-Induced Hemolytic Anemia

Aka: Drug-Induced Hemolytic Anemia, Medication Causes of Hemolytic Anemia, Drug Induced Immune-Mediated Hemolysis, Drug-Induced Immune Hemolytic Anemia, Drug-Induced Autoimmune Hemolytic Anemia, Drug-Induced Thrombotic Microangiopathic Anemia

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II. Differential Diagnosis

  1. See Hemolytic Anemia
  2. Autoimmune Hemolytic Anemia
  3. Methemoglobinemia
  4. G6PD Deficiency

III. Mechanisms

  1. Drug-absorption or Hapten-induced
    1. Medication coats Red Blood Cell surface
    2. Induces IgG Antibody production
  2. Immune-complex
    1. Drug stimulates IgM production and binding
    2. Drug-IgM complex binds RBC and complement induced
  3. Autoantibody
    1. Drug stimulates IgG production against RBC membrane

IV. Causes: By Mechanism

  1. Immune Hemolytic Anemia
    1. Beta-Lactamase Inhibitors (e.g. Sulbactam, Clavulanic Acid, Tazobactam)
    2. Cefotetan (common)
    3. Ceftriaxone (common)
    4. Fludarabine
    5. Intravenous Immunoglobulin (IV Ig)
    6. Methyldopa (common in past)
    7. NSAIDs (common)
    8. Penicillin (common in past)
    9. Piperacillin with Tazobactam or Zosyn (common)
  2. Thrombotic Microangiopathic Anemia (only 5% of MAHA Cases)
    1. Adalimumab (Humira)
    2. Bupropion (Wellbutrin)
    3. Chemotherapy
    4. Clopidogrel (Plavix)
    5. Cocaine
    6. Covid Vaccine (AstraZeneca and Johnson and Johnson Vaccine induced immune TTP, 5 to 30 days after dose)
    7. Cyclosporine (common cause)
    8. Gemcitabine (Gemzar)
    9. Ibuprofen
    10. Interferon
    11. Mefloquine
    12. Methylenedioxymethamphetamine (MDMA, Ecstacy)
    13. Metronidazole (Flagyl)
    14. Nitrofurantoin (Macrobid)
    15. Oxaliplatin (Eloxatin)
    16. Quetiapine (Seroquel)
    17. Quinine (common cause)
    18. Simvastatin (Zocor)
    19. Tacrolimus (Prograf, common cause)
    20. Trimethoprim Sulfamethoxazole (Bactrim, Septra)
  3. Oxidation Hemolysis
    1. Dapsone
    2. Nitrofurantoin
    3. Nitrous Oxide Abuse
    4. Phenazopyridine
    5. Primaquine
    6. Ribavirin
    7. Rifampin

V. Causes: Extravascular (IgG) vs Intravascular Hemolysis (C3)

  1. Positive Anti-IgG (Extravascular Hemolysis)
    1. Alpha-Methyldopa
    2. Ampicillin
    3. Carbenicillin
    4. Diclofenac
    5. Ibuprofen
    6. Interferon alfa
    7. Levodopa
    8. Mefenamic Acid
    9. Methicillin
    10. Penicillin
    11. Procainamide
  2. Positive Anti-C3 (Intravascular Hemolysis)
    1. Acetaminophen
    2. Chlorpromazine
    3. Fluorouracil
    4. Hydrochlorothiazide
    5. Hydralazine
    6. Insulin
    7. Isoniazid
    8. Melphalan
    9. Phenacetin
    10. Probenacid
    11. Quinidine
    12. Quinine
    13. Rifampin
    14. Streptomycin
    15. Sulfonamides
    16. Sulindac
    17. Tetracycline

VI. References

  1. Ford (2001) Clinical Toxicology, p. 201-3
  2. Dhaliwal (2004) Am Fam Physician 69:2599-606 [PubMed]
  3. Lubran (1989) Ann Clin Lab Sci 19:114-21 [PubMed]

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