What medications can cause thrombocytopenia (low platelet count)?

From the Guidelines

Drugs that can produce thrombocytopenia include heparin, chemotherapeutic agents, antibiotics, anticonvulsants, and certain antipsychotics, among others, with heparin being a well-known cause of heparin-induced thrombocytopenia (HIT) through immune-mediated mechanisms, as reported in a study published in the Journal of Thrombosis and Haemostasis 1.

Mechanisms and Examples

The mechanisms by which these drugs induce thrombocytopenia vary and can include immune-mediated destruction of platelets, direct bone marrow suppression, or other pathways. For instance:

• Heparin can trigger HIT, which is characterized by the formation of antibodies against complexes of platelet factor 4 and heparin, leading to platelet activation and thrombosis, as discussed in a guideline published in Blood Advances 1.
• Chemotherapeutic agents like carboplatin, cisplatin, gemcitabine, and oxaliplatin can cause thrombocytopenia by suppressing bone marrow production, a common side effect of these drugs.
• Antibiotics such as penicillins, cephalosporins, sulfonamides, vancomycin, and linezolid have been associated with thrombocytopenia, likely through immune-mediated mechanisms.
• Anticonvulsants, including carbamazepine, phenytoin, and valproic acid, can also reduce platelet counts, although the mechanisms may vary.

Management and Prevention

Drug-induced thrombocytopenia typically resolves within 7-14 days after discontinuing the offending medication, though recovery time can depend on the specific drug and mechanism involved, as noted in guidelines for the management of patients with non-ST-elevation acute coronary syndromes published in the Journal of the American College of Cardiology 1. Monitoring platelet counts is essential when starting these medications, especially in high-risk patients, and prompt discontinuation is necessary if thrombocytopenia develops.

Key Considerations

• The risk of thrombocytopenia is increased in patients treated with certain medications, and awareness of these risks can guide clinical decision-making.
• Thrombocytopenia can significantly increase the risk of thrombotic events, major bleeding, and in-hospital mortality, emphasizing the need for careful management.
• Direct thrombin inhibitors may be considered in preference to unfractionated heparin or low molecular weight heparin in patients with thrombocytopenia, as suggested by studies and guidelines, including those from the American Society of Hematology 1.

From the FDA Drug Label

ZYVOX has been associated with thrombocytopenia when used in doses up to and including 600 mg every 12 hours for up to 28 days. In Phase 3 comparator-controlled trials, the percentage of adult patients who developed a substantially low platelet count (defined as less than 75% of lower limit of normal and/or baseline) was 2.4% (range among studies: 0.3 to 10. 0%) with ZYVOX and 1.5% (range among studies: 0.4 to 7.0%) with a comparator. Thrombocytopenia associated with the use of ZYVOX appears to be dependent on duration of therapy, (generally greater than 2 weeks of treatment). The platelet counts for most patients returned to the normal range/baseline during the follow-up period.

Drugs producing thrombocytopenia:

• Linezolid (ZYVOX) is associated with thrombocytopenia, particularly with prolonged use (greater than 2 weeks of treatment) 2.
• The incidence of thrombocytopenia varies by population, with 2.4% of adult patients and 12.9% of pediatric patients developing substantially low platelet counts in clinical trials.
• Key points to consider:
  • Thrombocytopenia is a potential side effect of linezolid.
  • The risk of thrombocytopenia increases with longer treatment duration.
  • Platelet counts typically return to normal after treatment is stopped.

From the Research

Drugs Producing Thrombocytopenia

• Heparin is a common medication that can cause thrombocytopenia, specifically heparin-induced thrombocytopenia (HIT) 3, 4, 5, 6, 7
• HIT is an immune-mediated adverse drug reaction that results in thrombocytopenia and potentially catastrophic thrombosis 5
• The development of platelet-activating antibodies against multimolecular complexes of platelet factor 4 and heparin is the cause of HIT 5, 7

Diagnosis and Treatment

• The "4 Ts" score is recommended to identify patients at increased likelihood of HIT: thrombocytopenia, timing of platelet count fall, thrombosis or other complications, and other causes for thrombocytopenia 3, 5
• An immunoassay and functional assay are recommended to confirm or refute the diagnosis of HIT in patients with an intermediate or high probability 4Ts Score 5
• Heparin avoidance and initiation of nonheparin anticoagulation are the mainstays of acute HIT management 4, 5, 6
• Alternative anticoagulants such as lepirudin, argatroban, bivalirudin, or fondaparinux can be used to treat HIT 3, 4

Thrombosis in HIT

• Thrombosis is a central and unpredictable feature of HIT, and despite optimal management, disease morbidity and mortality from thrombosis remain high 7
• The hypercoagulable state in HIT is biologically distinct from other thrombophilic disorders, and clinical complications are directly attributable to circulating ultra-large immune complexes 7