What is a commonly used drug that can cause thrombocytopenia?

Heparin is the Commonly Used Drug That Causes Thrombocytopenia

The correct answer is D. Heparin. Heparin is a commonly used anticoagulant that can cause immune-mediated thrombocytopenia known as heparin-induced thrombocytopenia (HIT), which is a potentially devastating prothrombotic adverse drug reaction 1, 2.

Mechanism and Clinical Significance of HIT

Heparin-induced thrombocytopenia is caused by the formation of antibodies against the heparin-platelet factor 4 complex, which can lead to:

• Platelet activation and aggregation
• Paradoxical thrombosis despite low platelet counts
• Significant morbidity and mortality due to life and limb-threatening thrombotic complications 1

The incidence of HIT varies by patient population:

• Women have twice the risk of developing HIT compared to men 2
• Moderate thrombocytopenia (platelet counts between 100,000/mm³ and 50,000/mm³) occurs at a rate of 3.0% in surgical patients receiving fondaparinux 3
• Severe thrombocytopenia (platelet counts less than 50,000/mm³) occurs at a rate of 0.2% in patients receiving fondaparinux 3

Diagnostic Features of HIT

HIT has distinctive clinical features that help differentiate it from other causes of thrombocytopenia:

• Timing: Typically occurs 5-10 days after heparin initiation, but can occur rapidly within 24 hours in patients with recent heparin exposure or be delayed up to 3 weeks after heparin cessation 2
• Platelet count: Generally moderate thrombocytopenia (rarely below 20,000/μL) with a decrease of >50% from baseline 1
• Thrombosis: Paradoxically increased risk of venous and arterial thrombosis despite low platelet counts 1
• Clinical assessment: The 4T score is recommended to determine the clinical probability of HIT 1

Management of Suspected or Confirmed HIT

When HIT is suspected or confirmed:

1. Immediately discontinue all forms of heparin (including heparin flushes and heparin-coated catheters) 2
2. Initiate alternative anticoagulation with one of the following:
   • Direct thrombin inhibitors (argatroban, lepirudin, bivalirudin) 1
   • Factor Xa inhibitors (fondaparinux) 1
   • For patients with renal insufficiency, argatroban is preferred 1
3. Monitor platelet counts closely and discontinue therapy if platelet count falls below 100,000/mm³ 3
4. Avoid warfarin in the acute phase of HIT as it can lead to venous limb gangrene 4

Other Drugs and Thrombocytopenia

While the other options can affect platelets, they are not as strongly associated with immune-mediated thrombocytopenia as heparin:

• Aspirin (option B): Can affect platelet function but does not typically cause significant thrombocytopenia
• Ibuprofen (option A): Rarely causes thrombocytopenia
• Warfarin (option C): Can cause skin necrosis but is not typically associated with thrombocytopenia

Common Pitfalls in HIT Management

• Delayed recognition of HIT, often not suspected until after thrombotic complications occur 5
• Continued heparin administration after HIT is suspected 5
• Infrequent or delayed use of alternative anticoagulants 5
• Inappropriate use of warfarin in acute HIT 4

HIT remains an underdiagnosed and undertreated condition despite its significant clinical impact 6. Prompt recognition, laboratory testing, and alternate anticoagulation are essential for reducing morbidity and mortality in affected patients.