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Warfarin-Induced Skin Necrosis and Venous Limb Gangrene in the Setting of Heparin-Induced Thrombocytopenia
Abhay F. Srinivasan, MD;
Lawrence Rice, MD;
John R. Bartholomew, MD;
Chandhiran Rangaswamy, MD;
Lucy La Perna, DO;
James E. Thompson, MD;
Scott Murphy, MD;
Kelty R. Baker, MD
Arch Intern Med. 2004;164:66-70.
Background Heparin-induced thrombocytopenia (HIT) is a common, often catastrophic, syndrome that produces the most hypercoagulable of states. Emerging therapeutic strategies use alternative anticoagulants; warfarin's place is being reexamined. Early in the course of warfarin therapy, there may be net procoagulant effects because of the inhibition of protein C. With HIT, it has been suggested that unopposed warfarin can precipitate venous limb gangrene. There are also reports of warfarin-induced skin necrosis. We seek to confirm and increase awareness of the risks of warfarin with HIT.
Methods We describe 6 patients with HIT seen at 3 medical centers in whom frank or impending venous limb gangrene, central skin necrosis, or both were temporally related to warfarin initiation.
Results At warfarin initiation, 5 patients had recognized HIT and 1 had it recognized later. Complications emerged after 2 to 7 days, and consisted of warfarin-induced skin necrosis (n = 5) and venous limb gangrene (n = 2); 1 patient had both. This emerged with unopposed warfarin in 4 patients and as a direct thrombin inhibitor was being withdrawn in 2. All had supratherapeutic international normalized ratios. One patient required leg and breast amputations, and another one died.
Conclusions Because of the early effects on protein C, warfarin can precipitate venous limb gangrene and/or skin necrosis in the extreme hypercoagulable milieu of HIT. With HIT, unopposed warfarin should be avoided and caution is needed during transition from a direct thrombin inhibitor. Warfarin should be initiated at modest doses in patients with HIT after platelet recovery. Implications extend to warfarin initiation with other thrombotic diatheses.
From the Section of Hematology-Oncology, Department of Medicine, Baylor College of Medicine, Houston, Tex (Drs Srinivasan, Rice, and Baker); the Section of Vascular Medicine, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio (Drs Bartholomew and La Perna); the Division of Cardiology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor (Dr Rangaswamy); the Division of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia (Dr Thompson); and American Red Cross Blood Services and the Department of Medicine, University of Pennsylvania, Philadelphia (Dr Murphy). Drs Rice and Bartholomew have been consultants for and on the speakers bureau of Berlex Pharmaceuticals (which markets lepirudin for heparin-induced thrombocytopenia) and GlaxoSmithKline (which markets argatroban for heparin-induced thrombocytopenia); Dr Rice has received research support (not for this study) from GlaxoSmithKline; and Drs Rice and Bartholomew have been consultants for The Medicines Company (which markets bivalirudin for percutaneous coronary intervention in patients with heparin-induced thrombocytopenia).
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