Drug Induced Platelet Dysfunction

Aka: Drug Induced Platelet Dysfunction, Drug Induced Platelet Destruction, Drug induced Thrombocytopenia, Drug-Induced Thrombocytopenia, Thrombocytopenia caused by Medications

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II. Pathophysiology

  1. Isolated Low Platelets without affected other cell lines is common in Drug-Induced Thrombocytopenia
    1. Outside of bleeding and Bruising, patients often appear otherwise well
    2. Contrast with more serious Thrombocytopenia Causes (e.g. DIC, TTP)
  2. Two mechanisms of Drug induced Thrombocytopenia
    1. Immune Mediated Thrombocytopenia
      1. Antibodies form to Platelet specific Glycoprotein complexes
    2. Non-Immune Mediated Thrombocytopenia
      1. Drug-induced direct toxicity to Platelets or Megakaryocytes

III. Causes: Thrombocytopenia

  1. Chemotherapeutic agents
    1. Alkylating Agents
    2. Antimetabolites
    3. Interferon alpha
    4. Fludarabine
    5. Oxaliplatin
    6. Bleomycin
    7. Rituximab
    8. Trastuzumab
  2. Antibiotics
    1. Sulfonamides (e.g. Trimethoprim-Sulfamethoxazole or Bactrim)
    2. Penicillins
    3. Cephalosporins
    4. Rifampin
    5. Vancomycin
    6. Fluoroquinolones
    7. Linezolid
    8. Ganciclovir
  3. Cardiovascular Agents
    1. Captopril
    2. Thiazide Diuretics (Hydrochlorothiazide, Chlorthalidone)
    3. Spironolactone
    4. Furosemide (Lasix)
    5. Amiodarone
    6. Abciximab (ReoPro)
    7. Glycoprotein IIB/IIIA Inhibitor (Eptifibatide or Integrilin, Tirofiban)
    8. Digoxin
    9. Methyldopa
    10. Procainamide
    11. Cinchona alkaloids (Quinidine, Quinine, Tonic Water)
  4. H2 Antagonists
    1. Cimetidine (Tagamet)
    2. Ranitidine (Zantac)
  5. Neurologic agents (esp. antiepileptic agents)
    1. Phenytoin (Dilantin)
    2. Valproic Acid (Depakene)
    3. Lamotrigine (Lamictal)
    4. Carbamazepine (Tegretol)
    5. Levetiracetam (Keppra)
  6. Psychiatric Agents
    1. Barbiturates
    2. Benzodiazepines (Diazepam, Lorazepam)
    3. Chlorpromazine
    4. Citalopram
    5. Haloperidol
    6. Olanzapine (Zyprexa)
    7. Risperidone (Risperdal)
  7. Rheumatologic Agents
    1. Acetaminophen (autoimmune mechanism)
    2. NSAIDs (e.g. Ibuprofen, Naproxen, Indomethacin, Piroxicam, Diclofenac)
    3. Gold Salts
    4. Sulfasalazine (Azulfidine)
  8. Endocrine Agents
    1. Estrogens
    2. Propylthiouracil
  9. Herbals
    1. Cranberry Juice
    2. Jui herbal tea
    3. Lupinus termis bean
    4. Cow's Milk
    5. Tahini (sesame seed paste)
    6. Other Herbals may also be causes (e.g. chromium, Echinacea, hypericum, nicotinamide, Cupressus funebris)
  10. Immunizations
    1. MMR Vaccine
    2. Varicella Vaccine
    3. H1N1 Influenza Vaccine
  11. Miscellanous Agents
    1. See Drug-Induced Thrombotic Microangiopathic Anemia
    2. Chronic Alcohol Abuse
    3. Quinine
    4. Heparin Induced Thrombocytopenia
      1. Occur in 5% of patients on >5 days Heparin
      2. In vivo Platelet aggregation due to immune complexes against Platelet factor 4 (PF4) and Heparin

IV. Causes: Platelet Impaired Function

  1. Common causes
    1. Consider agents that affect coagulation (Heparin, Warfarin)
    2. Aspirin
    3. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
    4. Clopidogrel (Plavix)
  2. Herbals
    1. Garlic
      1. Cloves 2/day (longterm)
      2. Hold for 7 days before high bleeding risk procedures (e.g. Lumbar Puncture)
    2. Ginkgo Biloba
      1. Extract 120-240 mg/day
      2. Hold for 36 hours before high bleeding risk procedures (e.g. Lumbar Puncture)
    3. Ginseng
      1. Extract 200 mg/day (or 1-2 g root/day)
      2. Hold for 24 hours before high bleeding risk procedures (e.g. Lumbar Puncture)
    4. References
      1. (2025) Bleeding Risk Bedside Procedures, Hospital Procedures Course
      2. Horlocker (2010) Reg Anesth Pain Med 35(1):64-101 +PMID: 20052816 [PubMed]
  3. Other causes
    1. Antidepressants
      1. Tricyclic Antidepressants
      2. Selective Serotonin Reuptake Inhibitors
    2. Antihistamines
      1. Azatadine
      2. Brompheniramine
      3. Clemastine fumarate
    3. Clofibrate
    4. Dipyridamole
    5. Furosemide (Lasix)
    6. Nitrofurantoin (Furadantin)
    7. Propranolol
    8. Sulfinpyrazone

V. Course

  1. Platelet Count rarely falls below 20,000/uL in Drug induced Thrombocytopenia
  2. Onset within 3 to 10 days of starting the medication
  3. Expect recovery in 7-14 days after discontinuation of medication (4 to 5 medication half-lives)
    1. Consider alternative Thrombocytopenia Causes when Thrombocytopenia persists after stopping suspected medication

VI. Management

  1. Discontinue offending agent and recheck Platelet Count in 1 week
  2. Consider drug-specific antiplatelet Antibody testing when patient is on multiple medications that may cause Thrombocytopenia
  3. See Thrombocytopenia
  4. See Thrombocytopenia Causes

VII. Resources

  1. Platelets on the Web
    1. https://ouhsc.edu/platelets/ditp.html

VIII. References

  1. Merrill and Gillen (2016) Crit Dec Emerg Med 30(3): 3-8
  2. Kenney (2009) Arch Pathol Lab Med 133(2): 309-14 [PubMed]
  3. Gauer (2022) Am Fam Physician 106(3): 288-98 [PubMed]

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