Warfarin-induced limb gangrene in the setting of lung adenocarcinoma.

A 53-year-old man with lung adenocarcinoma developed pulmonary embolism and bilateral popliteal venous thrombosis. Treated with intravenous unfractionated heparin and discharged home on warfarin, he returned a week later with extending thrombosis. Treatment with heparin followed by warfarin was reinitiated. Twenty-four hours following the re-administration of warfarin, the patient's INR increased to 14.5. The platelet count dropped by more than 50%, and he developed venous limb gangrene of the left leg and skin necrosis of the right leg. Heparin-induced thrombocytopenia was ruled out, and coagulation studies showed a severe depletion of protein C as well as increased thrombin generation. The patient was transfused with fresh frozen plasma, and vitamin K was given. Heparin was continued, and after 4 weeks, the patient improved markedly showing only minimal necrosis of the toes. Venous limb gangrene is a major complication associated with warfarin therapy. Its pathogenesis is explained by a transient hypercoagulable state produced by protein C depletion that leads to microvascular thrombi progressing to venous limb gangrene. The present case emphasizes the importance of careful anticoagulation with heparin followed by slow initiation of low-dose warfarin, in order to minimize thrombotic complications.

Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study.

Among patients with von Willebrand disease (VWD) who are unresponsive to desmopressin therapy, replacement with plasma-derived concentrates is the treatment of choice. Because prospective studies are lacking, such treatment has been largely empirical. A multicenter, prospective study has been conducted in 81 patients with VWD (15 patients with type 1, 34 with type 2, and 32 with type 3 disease) to investigate the efficacy of a high-purity factor VIII/von Willebrand factor (FVIII/VWF) concentrate for treatment of bleeding and surgical prophylaxis. Two preparations of the concentrate-one virally inactivated with solvent detergent, the other with an additional heat-treatment step--were evaluated. Pharmacokinetic parameters were similar for both preparations. Using pre-established dosages based on the results of pharmacokinetic studies, 53 patients were administered either preparation for the treatment of 87 bleeding episodes, and 39 patients were treated prophylactically for 71 surgical or invasive procedures. Sixty-five (74.7%) and 10 (11.5%) of the bleeding episodes were controlled with 1 or 2 infusions, respectively. Patients with severe type 3 VWD typically required more infusions and higher doses, at shorter time intervals, than did patients with generally milder types 1 and 2. Among patients undergoing surgical procedures, blood loss was lower than that predicted prospectively, and losses exceeding the predicted value did not correlate with the postinfusion skin bleeding time. In conclusion, the concentrate effectively stopped active bleeding and provided adequate hemostasis for surgical or invasive procedures, even in the absence of bleeding time correction.