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)

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