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血浆凝血与纤溶动力学I:凝血-纤溶系统时间进程的基本动力学模型及其在临床研究中的潜在应用。

Kinetics of plasma coagulation and lysis I: Basic kinetic model for time course of coagulation-lysis systems and its potential application to clinical studies.

作者信息

Garrett E R, Daver J, Desnoyers P, Kosser M, Vincent M

出版信息

J Pharm Sci. 1978 Feb;67(2):145-51. doi: 10.1002/jps.2600670206.

DOI:10.1002/jps.2600670206
PMID:621627
Abstract

The time courses of coagulation and coagulation-lysis were spectrophotometrically monitored after the addition of thrombin or thrombin-streptokinase to plasma, diluted 1:5 with normal saline, obtained from normal and presumably abnormal subjects. The kinetics of clotting, after an initial lag period of 0.5-1.5 min, demonstrated essentially first-order dependence on the amount of fibrinogen available to form the clot, and the asymptotic absorbance was independent of thrombin concentration. The rate of clotting was a function of added thrombin, and the ratios of the rate constants at 2.5 and 1.25 units of thrombin/ml of undiluted plasma were 1.65 +/- 0.03 SEM. At early times, the coagulation-lysis curve with thrombin-streptokinase could be superimposed on the clotting curve with thrombin alone for a given plasma with minor compensation for variable lag times. Subsequently, the curves diverged; lysis was monitored by the decrease in absorbance of the coagulation-lysis system. The rate of fibrinolysis increased with streptokinase concentration and was a function of the extent of lysis, and it permitted the description of the kinetics of lysis by a pseudoautocatalytic mechanism where the bimolecular rate constant appears proportional to streptokinase concentration. Ranges of clotting and lytic parameters for the plasma of normal subjects are given, and their potential use in diagnosing abnormalities is described.

摘要

向取自正常和疑似异常受试者、用生理盐水按1:5稀释的血浆中加入凝血酶或凝血酶-链激酶后,用分光光度法监测凝血和凝血溶解的时间进程。凝血动力学在最初0.5 - 1.5分钟的延迟期后,显示出对可用于形成凝块的纤维蛋白原量基本上呈一级依赖性,并且渐近吸光度与凝血酶浓度无关。凝血速率是添加的凝血酶的函数,在未稀释血浆中凝血酶浓度为2.5和1.25单位/毫升时,速率常数之比为1.65±0.03(标准误)。在早期,对于给定血浆,凝血酶-链激酶的凝血-溶解曲线可以叠加在仅用凝血酶的凝血曲线上,只是对不同的延迟时间进行了少量补偿。随后,曲线分开;通过凝血-溶解系统吸光度的降低来监测溶解。纤维蛋白溶解速率随链激酶浓度增加,并且是溶解程度的函数,这使得可以通过假自催化机制来描述溶解动力学,其中双分子速率常数似乎与链激酶浓度成正比。给出了正常受试者血浆的凝血和溶解参数范围,并描述了它们在诊断异常中的潜在用途。

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