重组人活化蛋白C、肝素和水蛭素在脐带血与成人血浆中的情况

Recombinant human activated protein C, heparin and melagatran in umbilical cord versus adult plasma.

作者信息

Koestenberger Martin, Cvirn Gerhard, Gallistl Siegfried, Kutschera Joerg, Muntean Wolfgang

机构信息

Department of Paediatrics, Ludwig Boltzmann Research Institute for Paediatric Haemostasis and Thrombosis, Medical University of Graz, Auenbruggerplatz 30, A-8036 Graz, Austria.

出版信息

Acta Paediatr. 2005 Jul;94(7):884-9. doi: 10.1111/j.1651-2227.2005.tb02006.x.

DOI:10.1111/j.1651-2227.2005.tb02006.x

PMID:16188810

Abstract

AIM

We investigated the anticoagulant effects of recombinant human activated protein C (rhAPC), unfractionated heparin (UH) and melagatran (a new direct thrombin inhibitor [DTI]), when administered individually and in combinations of rhAPC with either UH or melagatran, in umbilical cord and adult plasma. rhAPC is a promising candidate treatment to improve the outcome of severe sepsis in neonates and adults; the DTI melagatran represents a potential advance in antithrombotic therapy.

METHODS

The anticoagulant efficacy of these drugs was measured using the standard coagulation assays activated partial thromboplastin time (aPTT) and prothrombin time (PT).

RESULTS

Administered individually, rhAPC, UH and melagatran dose-dependently prolonged aPTT to a significantly greater extent in umbilical cord than in adult plasma. Melagatran alone, but not rhAPC or UH alone, dose-dependently prolonged the PT in both umbilical cord and adult plasma. Combining rhAPC with either UH or melagatran significantly augmented aPTT prolongation in both umbilical cord and adult plasma.

CONCLUSION

Our results, which facilitate estimation of rhAPC and melagatran dose requirements in umbilical cord plasma, may be of benefit in critically sick newborns with severe sepsis.

摘要

目的

我们研究了重组人活化蛋白C（rhAPC）、普通肝素（UH）和 melagatran（一种新型直接凝血酶抑制剂[DTI]）在脐带血和成人血浆中单独使用以及 rhAPC 与 UH 或 melagatran 联合使用时的抗凝作用。rhAPC 是改善新生儿和成人严重脓毒症预后的一种有前景的候选治疗药物；DTI melagatran 代表了抗血栓治疗的一项潜在进展。

方法

使用活化部分凝血活酶时间（aPTT）和凝血酶原时间（PT）这两种标准凝血试验来测定这些药物的抗凝疗效。

结果

单独给药时，rhAPC、UH 和 melagatran 剂量依赖性地延长 aPTT，在脐带血中延长的程度明显大于成人血浆。单独使用 melagatran 可剂量依赖性地延长脐带血和成人血浆中的 PT，但单独使用 rhAPC 或 UH 则无此作用。rhAPC 与 UH 或 melagatran 联合使用可显著增强脐带血和成人血浆中 aPTT 的延长。