What medications can cause thrombocytopenia (low platelet count)?

From the Guidelines

Medications such as heparin, quinidine, sulfonamides, and vancomycin are well-known causes of thrombocytopenia, and their use should be carefully monitored to minimize the risk of thrombocytopenia. Thrombocytopenia can be caused by numerous medications through various mechanisms.

• Common culprits include heparin, which causes heparin-induced thrombocytopenia through immune-mediated platelet destruction 1.
• Other anticoagulants like glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) can also reduce platelet counts.
• Antibiotics that frequently cause thrombocytopenia include sulfonamides, vancomycin, linezolid, and rifampin 1.
• Chemotherapeutic agents like carboplatin, cisplatin, and gemcitabine directly suppress bone marrow production of platelets.
• Anticonvulsants (carbamazepine, phenytoin, valproic acid), antipsychotics (clozapine, chlorpromazine), and cardiac medications (quinidine, procainamide) are additional causes.
• NSAIDs, especially quinine and acetaminophen, can trigger immune-mediated platelet destruction. Medications typically cause thrombocytopenia either through direct bone marrow suppression, immune-mediated destruction, or increased peripheral consumption of platelets.
• Drug-induced thrombocytopenia often resolves within 5-10 days after discontinuing the offending medication, though recovery time varies based on the specific drug and mechanism involved 1. Monitoring platelet counts is essential when starting medications known to cause thrombocytopenia, and the most recent study 1 suggests that even in patients with thrombocytopenia, life-saving interventions such as anticoagulants and antiplatelet agents should not be denied due to the risk of bleeding. In patients with thrombocytopenia, the use of anticoagulants and antiplatelet agents requires careful consideration of the risk of bleeding versus the risk of thrombotic events, and reduced doses may be necessary in patients with severe thrombocytopenia 1.

From the FDA Drug Label

If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely.

• Thrombocytopenia can be caused by carbamazepine as it may exhibit low or decreased platelet counts, and the patient should be monitored closely.
• Heparin may also cause thrombocytopenia, as it can lead to HIT and HITT, including delayed onset cases.
• The decision to use these medications should be made with caution, and patients should be closely monitored for signs of thrombocytopenia 2, 3.

From the Research

Medication Causes of Thrombocytopenia

• Thrombocytopenia can be caused by the use of certain drugs, with the mechanism being either a decrease in platelet production or an increased destruction 4.
• The drug classes most often associated with drug-induced immune thrombocytopenia include:
  • Cinchona alkaloid derivatives (quinine, quinidine)
  • Sulfonamides
  • NSAIDs
  • Anticonvulsants
  • Disease modifying antirheumatic drugs
  • Diuretics 4
• Other drugs that have been implicated in case reports of thrombocytopenia include valproic acid, which has been shown to cause thrombocytopenia in 12-18% of subjects receiving treatment 5.
• The underlying mechanism of drug-induced immune thrombocytopenia is not completely clarified, but at least three different types of antibodies appear to play a role, including hapten-dependent antibodies, drug-induced, platelet-reactive auto-antibodies, and drug-dependent antibodies 4.
• Targets for drug-dependent antibodies are glycoproteins on the cell membrane of the platelets, such as glycoprotein (GP) Ib/IX and GPIIb/IIIa 4.

Diagnosis and Treatment

• Diagnosis of drug-induced immune thrombocytopenia may consist of identifying clinical symptoms, a careful evaluation of the causal relationship of the suspected causative drug, general laboratory investigation, and platelet serology tests 4.
• Treatment of drug-induced immune thrombocytopenia typically involves withholding the causative drug, and in severe cases, platelet transfusion may be necessary 4, 6.
• The prognosis of drug-induced thrombocytopenia is generally excellent if the offending medication is discontinued promptly 6.

Risk Factors

• Advanced age, female gender, and high doses of valproate have been identified as risk factors for the development of thrombocytopenia during treatment with valproate 5.
• The clinical impact of the occurrence of thrombocytopenia during valproate treatment, such as the risk of life-threatening events, is not yet fully understood and requires further research 5.