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Drug Induced Thrombocytopenia

Drug induced thrombocytopenia can be caused by dozens of different medications and should be suspected in any patient who presents with acute thrombocytopenia of unknown origin. Typically, a patient will have taken the sensitizing drug for about 1 week or intermittently over a longer period of time before presenting with petechial hemorrhages and ecchymoses. Platelet inhibitors are the exception to this general rule because petechiae may occur within 1 or 2 days after an apparent first exposure. Systemic symptoms such as lightheadedness, chills, fever, nausea, and vomiting often precede bleeding. Severely affected individuals have florid purpura and bleeding from nose, gums and gastrointestinal or urinary tract. In adults, the presence of severe thrombocytopenia, with a platelet count <20,000/uL, increases the likelihood that a patient has drug induced thrombocytopenia. If the causative medication is promptly discontinued, symptoms often resolve within 2 days and the platelet count returns to normal within a week.

The medications most commonly associated with drug induced thrombocytopenia are listed below.

Analgesics

  • Acetaminophen
  • Diclofenac
  • Ibuprofen
  • Naproxen
  • Propoxyphene

Anticonvulsant & sedatives

  • Carbamazepine
  • Diazepam
  • Fentanyl
  • Phenytoin
  • Trimipramine
  • Valproic acid

Antimicrobial

  • Cephalosporins
  • Linezolid
  • Penicillins
  • Rifampin
  • Sulfonamides
  • Trimethoprim
  • Vancomycin

Cardiac

  • Amrinone
  • Beta blockers
  • Digoxin
  • Procainamide

Chemotherapeutic

  • Fludarabine
  • Oxaliplatin

Cinchona alkaloids

  • Quinine
  • Quinidine

Diuretics

  • Chlorothiazide
  • Furosemide
  • Hydrochlorothiazide

Heparins

  • Unfractionated
  • Low molecular weight

Histamine Receptor Antagonists

  • Cimetidine
  • Ranitidine

Immune Modulators

  • Cyclosporine
  • Interferon alpha & beta
  • Rituximab

Platelet Inhibitors

  • Abciximab
  • Clopidogrel
  • Dipyridamole
  • Eptifibatide
  • Tirofiban

Rheumatic

  • D-penicillamine
  • Gold salts
  • Infliximab

Many cases of drug induced thrombocytopenia are immune mediated and it is often possible to identify antibodies that react with normal platelets in the presence of the drug but not in its absence. In other cases with a high index of suspicion for drug induced thrombocytopenia, antibody tests are negative, probably because a drug metabolite produced in vivo, rather than the parent drug, is the sensitizing agent. Testing for drug induced platelet antibodies, with the exception of heparin, is technically demanding and only available at a few reference laboratories. Therefore, it is not useful in the immediate care of a patient.

When there is uncertainty about the causative drug, all medications should be discontinued, and pharmacologic equivalents with different chemical structures substituted as necessary. Patients who present with severe thrombocytopenia and wet purpura should be treated with platelet transfusions because of the risk of fatal intracranial and intrapulmonary hemorrhage. The therapeutic benefit of corticosteroids and intravenous immune globulin has not been proven. Once established, drug sensitivity probably persists indefinitely and patients should be advised to avoid permanently the suspected medication.

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