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重组水蛭素用于治疗血液系统恶性肿瘤患者的弥散性血管内凝血

Recombinant hirudin for the treatment of disseminated intravascular coagulation in patients with haematological malignancy.

作者信息

Saito M, Asakura H, Jokaji H, Uotani C, Kumabashiri I, Morishita E, Yamazaki M, Aoshima K, Matsuda T

机构信息

Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.

出版信息

Blood Coagul Fibrinolysis. 1995 Feb;6(1):60-4. doi: 10.1097/00001721-199502000-00010.

Abstract

The purpose of this pilot study was to determine the effect of recombinant hirudin (r-hirudin) on coagulopathy and the relationship between concentrations of thrombin-antithrombin III (ATIII) complex (TAT) and thrombin-hirudin complex (THC) in patients with disseminated intravascular coagulation (DIC). Five patients with haematological malignancy associated with DIC were studied. r-Hirudin was administered by continuous intravenous infusion at a dose of 0.005 mg/kg/h for 4-9 days to each patient. Fibrin/fibrinogen degradation products (FDP), D-dimer, TAT and plasmin-alpha 2 antiplasmin complex (PAP) concentrations decreased after treatment with r-hirudin in four patients studied. However, in one patient, serum creatinine increased to 1.7 mg/dl and aPTT was prolonged to 74.4s. Statistical analysis disclosed significant positive correlations between plasma concentrations of hirudin and THC, and between concentrations of THC and TAT. The concentrations of THC were much higher than those of TAT. In conclusion, these findings indicate that r-hirudin more strongly inhibited thrombin than did ATIII without heparin, and that administration of r-hirudin to renal insufficiency required individual adjustment of dosage. The present findings also suggest that r-hirudin can be considered a new agent for the treatment of DIC.

摘要

本初步研究的目的是确定重组水蛭素(r-水蛭素)对弥散性血管内凝血(DIC)患者凝血病的影响,以及凝血酶-抗凝血酶III(ATIII)复合物(TAT)和凝血酶-水蛭素复合物(THC)浓度之间的关系。研究了5例与DIC相关的血液系统恶性肿瘤患者。对每位患者以0.005mg/kg/h的剂量持续静脉输注r-水蛭素,共4 - 9天。在所研究的4例患者中,用r-水蛭素治疗后纤维蛋白/纤维蛋白原降解产物(FDP)、D-二聚体、TAT和纤溶酶-α2抗纤溶酶复合物(PAP)浓度降低。然而,1例患者血清肌酐升至1.7mg/dl,活化部分凝血活酶时间(aPTT)延长至74.4秒。统计分析显示,水蛭素血浆浓度与THC浓度之间,以及THC浓度与TAT浓度之间存在显著正相关。THC的浓度远高于TAT的浓度。总之,这些发现表明,在无肝素的情况下,r-水蛭素比ATIII更强烈地抑制凝血酶,并且对肾功能不全患者给予r-水蛭素需要个体化调整剂量。目前的研究结果还表明,r-水蛭素可被视为治疗DIC的一种新药。

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