What medications can cause thrombocytopenia?

Drugs Causing Thrombocytopenia

Unfractionated heparin (UFH) is the most common and dangerous cause of drug-induced thrombocytopenia, affecting up to 15% of patients, and paradoxically causes life-threatening thrombosis rather than bleeding. 1

High-Risk Anticoagulants and Antiplatelet Agents

Heparin Products

• Unfractionated heparin (UFH) causes heparin-induced thrombocytopenia (HIT) in up to 15% of patients, making it the most frequent culprit, with thrombocytopenia typically developing 5-10 days after initiation 1, 2
• Low molecular weight heparin (LMWH) causes HIT less frequently than UFH but through the same immune mechanism involving PF4-heparin antibody complexes 1, 2
• Fondaparinux does NOT cause HIT and serves as a safe alternative in patients at risk 1, 2
• HIT may occur earlier (within 24 hours) in patients recently exposed to heparin within the previous 3 months, or may be delayed beyond 3 weeks, especially with LMWH 3, 4

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, 2
• These agents cause early and often profound thrombocytopenia, requiring immediate discontinuation if platelet count drops below 100,000/μL or decreases by >50% 3, 2

Immunosuppressive and Transplant Medications

• Azathioprine and mycophenolate mofetil cause myelosuppression leading to thrombocytopenia, anemia, and leucopenia 1
• Sirolimus has dose-dependent association with thrombocytopenia 1
• ACE inhibitors and angiotensin receptor blockers (ARBs) may be associated with post-transplant thrombocytopenia 1

Chemotherapy Agents

• Antimitotic chemotherapies (5-fluorouracil, capecitabine) cause thrombocytopenia through bone marrow suppression 4, 2
• Paclitaxel causes thrombocytopenia, particularly when combined with other agents, requiring dose reduction for platelet counts <50,000/μL 2

Antimicrobial Agents

• Rifampin causes thrombocytopenia and requires special consideration when used with anticoagulants 1
• Ganciclovir (antiviral) causes myelosuppression contributing to thrombocytopenia 1

Critical Diagnostic Approach

For Suspected HIT

• Use the 4Ts score to assess pretest probability, evaluating: (1) degree of Thrombocytopenia, (2) Timing of platelet fall, (3) presence of Thrombosis, and (4) absence of oTher causes 3, 1, 4
• Do NOT order HIT testing or initiate empiric treatment in patients with low-probability 4Ts score 1
• Thrombocytopenia in HIT is typically moderate (30-70 G/L, rarely <20 G/L) with a >50% decrease from baseline 3

Common Pitfalls to Avoid

• Early thrombocytopenia (within first 2 days of UFH) may represent direct heparin effect or hemodilution, not immune HIT 3, 4
• Post-transfusion purpura presents with sudden, major platelet decrease and hemorrhagic context, requiring urgent diagnosis and specific treatment 3
• Antiphospholipid syndrome, thrombotic thrombocytopenic purpura (TTP), and DIC can mimic HIT with both thrombocytopenia and thrombosis 3, 4
• Perioperative hemodilution, platelet consumption in extracorporeal circuits (ECMO, ventricular assist devices, cardiac surgery) commonly cause thrombocytopenia in ICU patients 3, 4

Immediate Management Priorities

Universal First Step

• Discontinue the suspected causative drug immediately when drug-induced thrombocytopenia is identified—this is the cornerstone of management for all cases 1, 2

For Confirmed or Suspected HIT

• Stop ALL heparin products immediately, even before confirmatory testing 3, 2, 5
• Initiate alternative anticoagulation with direct thrombin inhibitors (argatroban, bivalirudin) or fondaparinux 3, 1
• Rivaroxaban (15 mg twice daily until day 21 or platelet recovery, then 20 mg daily for ≥1 month) is the most evaluated DOAC for HIT treatment 3
• Monitor platelet counts every 2-3 days from day 4 to day 14 in patients receiving heparin with HIT risk >1% 1

Critical Contraindications in HIT

• NEVER use vitamin K antagonists (warfarin) alone in acute HIT—they promote venous thrombosis progression, gangrene, and skin necrosis 3, 1
• Only start warfarin when platelet count recovers to >150,000/μL under cover of effective alternative anticoagulation 3, 1
• Do NOT transfuse platelets in acute HIT unless life-threatening or functional bleeding occurs 3, 1
• Do NOT prescribe oral antiplatelet agents to treat acute HIT 3
• Do NOT insert inferior vena cava filters in acute HIT 3

Platelet Transfusion Guidelines

• Reserve platelet transfusions for active hemorrhage, platelet counts <10,000/μL, or high-risk invasive procedures 1, 2
• For cancer patients with thrombocytopenia and acute coronary syndrome, use full-dose anticoagulation if platelet count >50,000/μL without bleeding 2

Antiplatelet Therapy Thresholds

• Dual antiplatelet therapy can be used for platelet counts >30,000/μL 2
• Aspirin alone for platelet counts >10,000/μL 2