What medications can cause thrombocytopenia (low platelet count)?

Medications That Cause Thrombocytopenia

Unfractionated heparin (UFH) is the most common and dangerous cause of drug-induced thrombocytopenia, affecting up to 15% of patients and carrying significant risk of life-threatening thrombotic complications rather than bleeding. 1

High-Risk Anticoagulants and Antiplatelet Agents

Heparin Products

• UFH causes heparin-induced thrombocytopenia (HIT) in up to 15% of patients, making it the single most important drug-induced thrombocytopenia to recognize due to its paradoxical thrombotic complications. 1, 2
• Low molecular weight heparin (LMWH) causes thrombocytopenia less frequently than UFH but through the same immune-mediated mechanism involving platelet factor 4 (PF4) antibodies. 1
• HIT typically develops 5-10 days after heparin initiation, though it may occur within 24 hours in patients with recent heparin exposure (within 3 months). 1, 3
• Fondaparinux does not cause HIT and serves as a safe alternative in patients at risk. 1, 2

Glycoprotein IIb/IIIa Inhibitors

• Abciximab, eptifibatide, and tirofiban cause severe thrombocytopenia (platelet count <50,000/μL) in 0.5% of patients and profound thrombocytopenia (<20,000/μL) in 0.2%. 1
• These agents cause early and often profound thrombocytopenia requiring immediate discontinuation if platelet count drops below 100,000/μL or decreases by >50%. 2

Antimicrobial and Immunosuppressive Agents

Antibiotics

• Linezolid causes thrombocytopenia in a duration-dependent manner, particularly with therapy exceeding 2 weeks, with 2.4% of adults developing substantially low platelet counts in clinical trials. 4
• Rifampin causes thrombocytopenia and requires special monitoring when combined with anticoagulants. 1

Immunosuppressants

• Azathioprine and mycophenolate mofetil cause dose-dependent myelosuppression leading to thrombocytopenia. 1
• Sirolimus demonstrates dose-dependent association with thrombocytopenia. 1
• Ganciclovir causes myelosuppressive thrombocytopenia. 1

Chemotherapy Agents

• Antimitotic chemotherapies including 5-fluorouracil (5-FU) and capecitabine cause thrombocytopenia through bone marrow suppression. 2
• Paclitaxel causes thrombocytopenia, particularly when combined with other agents, requiring dose reduction for platelet counts <50,000/μL. 2

Other Medication Classes

• ACE inhibitors and angiotensin receptor blockers (ARBs) may be associated with post-transplant thrombocytopenia. 1
• Quinine and quinidine (cinchona alkaloid derivatives) are frequently implicated in drug-induced immune thrombocytopenia. 5
• Sulfonamides, NSAIDs, anticonvulsants, and disease-modifying antirheumatic drugs are commonly associated with immune-mediated thrombocytopenia. 5

Clinical Recognition and Timing

• Drug-induced immune thrombocytopenia typically develops 5-10 days after drug administration with increased hemorrhage risk. 6
• Patients with platelet counts >50,000/μL are generally asymptomatic, while counts between 20,000-50,000/μL cause mild skin manifestations (petechiae, purpura, ecchymosis), and counts <10,000/μL carry high risk of serious bleeding. 7

Critical Management Principles

• Immediate discontinuation of the suspected causative drug is the cornerstone of management for all drug-induced thrombocytopenia. 1, 2
• For suspected or confirmed HIT, all heparin products must be stopped immediately and alternative anticoagulation with direct thrombin inhibitors (argatroban, lepirudin) or fondaparinux initiated, even before laboratory confirmation. 8, 2
• Platelet count monitoring every 2-3 days from day 4 to day 14 is recommended for patients receiving heparin with HIT risk >1%. 8
• Platelet transfusions should be reserved for active hemorrhage, platelet counts <10,000/μL, or high-risk invasive procedures. 8, 2
• High-dose intravenous immunoglobulin can be administered for severe thrombocytopenia with active bleeding. 1, 6

Important Caveats

• HIT is paradoxically prothrombotic rather than hemorrhagic—thrombotic complications are more common than bleeding despite low platelet counts. 6, 7
• Vitamin K antagonists (warfarin) should not be started until platelet counts recover to at least 150,000/μL in HIT patients to prevent venous limb gangrene. 8
• Pseudothrombocytopenia must be excluded by repeating platelet count in heparin or sodium citrate tubes before pursuing extensive workup. 7
• The 4Ts score should be used to estimate pretest probability of HIT before ordering laboratory testing to avoid overdiagnosis and unnecessary treatment with alternative anticoagulants. 1