Thrombotic Complications of Antithrombotic Therapy: A Paradox with Implications for Clinical Practice

Heparin and warfarin have been the standard therapy for thromboembolic disease for more than 50 years. During this time, the clinical indications for their use have expanded. Heparin is the standard initial therapy for acute venous thrombosis or pulmonary embolism; it is also widely used to treat acute coronary syndromes and prevent thrombosis during vascular surgery or angioplasty, ex vivo thrombi during cardiopulmonary bypass surgery and hemodialysis, and postoperative venous thromboembolism in high-risk patients. The use of warfarin has also expanded in recent years to include prevention of thromboembolic stroke in patients with atrial fibrillation, a condition that affects many thousands of elderly patients each year in the United States. The wider use of warfarin has been facilitated by the finding that the risk for bleeding is reduced (without loss of antithrombotic efficacy) when the warfarin dose is adjusted to achieve a less intense anticoagulant effect than had been used in North America in previous years [1].

Bleeding is the most common complication of treatment with heparin or warfarin. Aside from this, heparin and warfarin have had remarkably good safety records for 50 years. Nevertheless, two rare but serious nonhemorrhagic complications have been documented and widely reported: heparin-induced thrombocytopenia with thrombosis [2] and warfarin-induced skin necrosis [3]. Paradoxically, both of these complications are associated with thrombosis, the very problem that anticoagulant treatment is supposed to treat or prevent.

Heparin-induced thrombocytopenia occurs in 1% to 3% of patients who receive heparin for deep venous thrombosis [2]. It usually occurs more than 5 days after the start of heparin therapy but may occur earlier in patients who have had recent exposure to heparin. Heparin-induced thrombocytopenia is caused by heparin-dependent antibodies …