Schiele F, Vuillemenot A, Kramarz P, Kieffer Y, Soria J, Soria C, Camez A, Mirshahi M C, Bassand J P
Centre Hospitalier Saint Jacques, Service de Cardiologie, Besançon, France.
Thromb Haemost. 1994 May;71(5):558-62.
Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim of our study was to assess the pharmacokinetics, the results on the coagulation variables, and the safety of a recombinant hirudin (HBW 023) administered subcutaneously in patients suffering from deep vein thrombosis.
Recombinant hirudin (HBW 023) was administered subcutaneously to 10 patients with recent deep vein thrombosis, at a dose of 0.75 mg/kg of body weight twice daily for 5 days, after which standard heparin and acenocoumarol were introduced. Bilateral lower limb venography, and pulmonary angiography, and/or ventilation-perfusion lung scan were carried out on day 1 prior to recombinant hirudin injection and repeated on day 5. aPTT and recombinant hirudin plasma levels were serially assessed after the 1st and the 10th injections. Prothrombin fragments 1 + 2, thrombin-antithrombin III complexes, fibrin degradation products were collected on days 1 and 5.
Clinical evolution was uneventful in all but one patient who had a probable recurrence of pulmonary embolism on day 4. No hemorrhagic complication, no untoward biological event was observed. On days 5, Marder score was unchanged or had decreased. Plasma levels of recombinant hirudin peaked in between 3 and 4 h following the injection. aPTT values paralleled, and were significantly correlated with plasma levels of recombinant hirudin on day 1 as well on day 5 (r = 0.903, r = 0.948 respectively). Fragment 1 + 2, and thrombin antithrombin complexes non-significantly decreased from day 1 to day 5.
Subcutaneous administration of recombinant hirudin ensures prolonged stable plasma levels of recombinant hirudin which results in efficient anticoagulation. A dose-ranging study conducted with subcutaneous recombinant hirudin in comparison to conventional heparin therapy may answer the question as to efficacy.
重组水蛭素是一种纯的、特异性抗凝血酶，在治疗深静脉血栓形成方面可能比肝素更有效，但其半衰期短需要持续静脉输注，而皮下注射重组水蛭素可确保血浆水平稳定且持久。我们研究的目的是评估皮下注射重组水蛭素（HBW 023）在深静脉血栓形成患者中的药代动力学、对凝血变量的影响以及安全性。
对10例近期发生深静脉血栓形成的患者皮下注射重组水蛭素（HBW 023），剂量为0.75 mg/kg体重，每日2次，共5天，之后引入标准肝素和醋硝香豆素。在注射重组水蛭素前第1天和第5天进行双侧下肢静脉造影、肺血管造影和/或通气-灌注肺扫描。在第1次和第10次注射后连续评估活化部分凝血活酶时间（aPTT）和重组水蛭素血浆水平。在第1天和第5天收集凝血酶原片段1 + 2、凝血酶-抗凝血酶III复合物、纤维蛋白降解产物。
除1例患者在第4天可能复发肺栓塞外，所有患者临床病情平稳。未观察到出血并发症及不良生物学事件。在第5天，马德评分未改变或有所降低。重组水蛭素血浆水平在注射后3至4小时达到峰值。第1天和第5天，aPTT值与重组水蛭素血浆水平平行且显著相关（分别为r = 0.903，r = 0.948）。从第1天到第5天，片段1 + 2和凝血酶抗凝血酶复合物无显著下降。
皮下注射重组水蛭素可确保重组水蛭素血浆水平长时间稳定，从而实现有效的抗凝作用。与传统肝素治疗相比，用皮下重组水蛭素进行的剂量范围研究可能会回答疗效问题。
