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. Bupropion (Wellbutrin)
    2. Chemotherapy
    3. Clopidogrel (Plavix)
    4. Cocaine
    5. Cyclosporine (common cause)
    6. Ibuprofen
    7. Interferon
    8. Mefloquine
    9. Methylenedioxymethamphetamine (MDMA, Ecstacy)
    10. Metronidazole (Flagyl)
    11. Nitrofurantoin (Macrobid)
    12. Quetiapine (Seroquel)
    13. Quinine (common cause)
    14. Simvastatin (Zocor)
    15. Tacrolimus (Prograf, common cause)
    16. 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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Related Studies

Ontology: Drug-induced hemolytic anemia (C0272132)

Concepts Disease or Syndrome (T047)
SnomedCT 81711008
English Drug-induced hemolytic anemia, Drug-induced haemolyt anaemia, Drug-induced haemolyt anemia, drug-induced hemolytic anemia, anemia drugs hemolytic induced, drug induced hemolytic anemia, Haemolytic anaemia drug-induced, Hemolytic anemia drug-induced, Drug-induced haemolytic anaemia, Haemolytic anaemia due to drugs, Hemolytic anemia due to drugs (disorder), Hemolytic anemia due to drugs, Drug-induced hemolytic anemia, NOS, Hemolytic anemia due to drugs, NOS
Dutch hemolytische anemie geneesmiddelgeïnduceerd
French Anémie hémolytique médicamenteuse, Anémie hémolytique induite par un médicament
German haemolytische Anaemie arzneimittelbedingt, haemolytische Anaemie, arzneimittelbedingt
Italian Anemia emolitica da farmaci
Portuguese Anemia hemolítica farmacoinduzida
Spanish Anemia hemolítica inducida por fármacos, Anemia hemolítica autoinmune inducida por medicamentos, anemia hemolítica farmacógena, anemia hemolítica medicamentosa (trastorno), anemia hemolítica medicamentosa
Japanese ﾔｸｻﾞｲﾕｳﾊﾂｾｲﾖｳｹﾂｾｲﾋﾝｹﾂ, 薬剤誘発性溶血性貧血
Czech Léky indukovaná hemolytická anémie, Poléková hemolytická anémie
Hungarian gyógyszer-által kiváltott Haemolytikus anaemia, Haemolyticus gyógyszer-által kiváltott anaemia
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Drug-induced autoimmune hemolytic anemia (C0391817)

Concepts Pathologic Function (T046)
ICD10 D59.0
SnomedCT 191214001, 309742004
English Drug-induced autoim haem anaem, drug-induced autoimmune hemolytic anemia, drug-induced autoimmune hemolytic anemia (diagnosis), anemia hemolytic drug-induced autoimmune, Drug-induced autoimmune haemolytic anaemia (disorder), Drug-induced autoimmune haemolytic anaemia, Drug-induced autoimmune hemolytic anemia, Drug-induced autoimmune hemolytic anemia (disorder), anemia; hemolytic drug-induced, autoimmune
German Arzneimittelinduzierte autoimmunhaemolytische Anaemie
Korean 약물유발성 자가면역성 용혈성 빈혈
Dutch anemie; hemolytisch door geneesmiddelen, auto-immuun, Door geneesmiddelen geïnduceerde auto-immune hemolytische anemie
Spanish anemia hemolítica autoinmunitaria medicamentosa (trastorno), anemia hemolítica autoinmunitaria medicamentosa
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Drug-induced immune hemolytic anemia (C1096070)

Concepts Disease or Syndrome (T047)
SnomedCT 127059001
English Drug-induced immune hemolytic anemia, drug related immune hemolytic anemia, hemolytic anemia due to drug related immune complexes (diagnosis), hemolytic anemia due to drug related immune complexes, Immune hemolytic anemia drug-induced, Immune haemolytic anaemia drug-induced, Drug-induced immune haemolytic anaemia, Drug-induced immune hemolytic anemia (disorder)
Dutch immune hemolytische anemie geneesmiddelgeïnduceerd
French Anémie hémolytique immune induite par médicament, Anémie hémolytique médicamenteuse auto-immune
German haemolytische Anaemie, arzneimittelbedingt, immunhaemolytische Anaemie arzneimittelbedingt
Italian Anemia emolitica autoimmune da farmaci
Portuguese Anemia hemolítica imune induzida por fármacos, Anemia hemolítica imune farmacoinduzida
Spanish Anemia hemolítica autoinmune inducida por fármacos, Anemia hemolítica autoinmune medicamentosa, anemia hemolítica inmunitaria medicamentosa (trastorno), anemia hemolítica inmunitaria medicamentosa
Japanese 薬剤誘発性免疫性溶血性貧血, ﾔｸｻﾞｲﾕｳﾊﾂｾｲﾒﾝｴｷｾｲﾖｳｹﾂｾｲﾋﾝｹﾂ
Czech Imunitně podmíněná léky indukovaná hemolytická anémie, Imunitně podmíněná poléková hemolytická anémie
Hungarian Immunhaemolyticus gyógyszer-által kiváltott anaemia, Immun haemolytikus gyógyszer-által kiváltott anaemia
Derived from the NIH UMLS (Unified Medical Language System)

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