Whelen S, Carr M E
Department of Medicine, Medical College of Virginia Hospitals, Virginia Commonwealth University, Richmond, USA.
Angiology. 2001 Oct;52(10):711-5. doi: 10.1177/000331970105201008.
Treatment of critically ill patients who have heparin-induced thrombocytopenia and thrombosis (HITT) and also renal failure is a challenge. Recombinant hirudin (Refludan, Hoechst Marion Roussel) is a direct thrombin inhibitor indicated for anticoagulation in HITT and approved by the United States Food and Drug Administration. Because this drug is renally cleared, a single dose of hirudin may induce prolonged (up to one week) unpredictable anticoagulation in patients with renal insufficiency. There are a few case reports of patients with renal failure and suspected heparin-induced thrombocytopenia (HIT) in which patients were anticoagulated with Refludan for catheter thrombosis. There is no literature on the therapeutic use of Refludan to treat HITT in patients with diffuse thrombosis and renal failure. The authors report the case of a 44-year-old female dialysis patient with HITT and extensive life-threatening thrombosis. The patient developed common iliac vein occlusion extending to the right atrium with progressive right internal jugular vein thrombus developing while on heparin. Her platelet count dropped to 60,000/microL. She was lethargic and hemodynamically unstable. Refludan was initially given as a bolus of 0.2 mg/kg (total, 12 mg) at a 50% dose reduction based on the patient's ideal body weight. This dose was based on the published pharmacokinetics of Refludan in patients with renal failure. Only 2 additional boluses of 6 mg and 3 mg were needed to extend the duration of therapeutic anticoagulation (measured by PTT) to 140 hours. The patient improved both clinically and radiographically after the treatment with Refludan. There were no additional thromboembolic events or bleeding complications. The platelets returned to normal within a few days. The patient was transitioned to coumadin and discharged from the hospital. She remains stable at 1-year follow-up.
治疗患有肝素诱导的血小板减少症和血栓形成（HITT）且伴有肾衰竭的重症患者是一项挑战。重组水蛭素（Refludan，赫斯特·马里恩·罗塞尔公司）是一种直接凝血酶抑制剂，适用于HITT的抗凝治疗，并已获得美国食品药品监督管理局的批准。由于这种药物经肾脏清除，单剂量的水蛭素可能会在肾功能不全的患者中导致抗凝时间延长（长达一周）且难以预测。有一些关于肾衰竭且疑似肝素诱导的血小板减少症（HIT）患者的病例报告，这些患者因导管血栓形成而接受Refludan抗凝治疗。目前尚无关于Refludan用于治疗弥漫性血栓形成和肾衰竭患者的HITT的治疗用途的文献。作者报告了一例44岁女性透析患者，患有HITT且有广泛的危及生命的血栓形成。该患者在使用肝素期间出现了延伸至右心房的髂总静脉闭塞，并伴有右颈内静脉血栓逐渐形成。她的血小板计数降至60,000/微升。她嗜睡且血流动力学不稳定。最初根据患者的理想体重以50%的剂量减少给予Refludan推注，剂量为每千克0.2毫克（总计12毫克）。该剂量基于已发表的Refludan在肾衰竭患者中的药代动力学。仅需另外两次6毫克和3毫克的推注，即可将治疗性抗凝的持续时间（通过活化部分凝血活酶时间测量）延长至140小时。使用Refludan治疗后，患者在临床和影像学上均有改善。没有发生额外的血栓栓塞事件或出血并发症。血小板在几天内恢复正常。患者改用华法林并出院。在1年的随访中她保持稳定。
