Srinivasan Abhay F, Rice Lawrence, Bartholomew John R, Rangaswamy Chandhiran, La Perna Lucy, Thompson James E, Murphy Scott, Baker Kelty R
Section of Hematology-Oncology, Department of Medicine, Baylor College of Medicine, Houston, Tex. 77030, USA.
Arch Intern Med. 2004 Jan 12;164(1):66-70. doi: 10.1001/archinte.164.1.66.
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.
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.
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 This emerged with unopposed warfarin in 4 patients and as a direct thrombin inhibitor was being withdrawn in 2.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.
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.
肝素诱导的血小板减少症（HIT）是一种常见且往往具有灾难性的综合征，可导致最为高凝的状态。新出现的治疗策略采用替代抗凝剂；华法林的地位正在重新审视。在华法林治疗过程早期，由于蛋白C受到抑制，可能会产生促凝净效应。对于HIT，有人提出，单独使用华法林可引发肢体静脉坏疽。也有关于华法林诱导皮肤坏死的报道。我们旨在证实并提高对HIT患者使用华法林风险的认识。
我们描述了在3个医疗中心就诊的6例HIT患者，其明确的或即将发生的肢体静脉坏疽、中心性皮肤坏死或两者均与开始使用华法林在时间上相关。
开始使用华法林时，5例患者已确诊HIT，1例后来才确诊。并发症在2至7天后出现，包括华法林诱导的皮肤坏死（n = 5）和肢体静脉坏疽（n = 2）；1例患者两者均有。4例患者单独使用华法林时出现这种情况，2例患者在停用直接凝血酶抑制剂时出现。所有患者的国际标准化比值均高于治疗水平。1例患者需要进行腿部和乳房截肢，另1例死亡。
由于对华法林对蛋白C的早期影响，在HIT这种极高凝环境中，华法林可引发肢体静脉坏疽和/或皮肤坏死。对于HIT，应避免单独使用华法林，在从直接凝血酶抑制剂转换时需谨慎。血小板恢复后，HIT患者应以中等剂量开始使用华法林。这一结论也适用于其他血栓形成性疾病患者开始使用华法林的情况。
