Mathematical modeling of material-induced blood plasma coagulation
Mathematical modeling of material-induced blood plasma coagulation
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DOI：
10.1016/j.biomaterials.2005.06.021
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发表时间：
2006-02-01
期刊：
影响因子：
14
通讯作者：
Siedlecki, CA
中科院分区：
文献类型：
--
作者：
Guo, Z;Bussard, KM;Siedlecki, CA
当促凝血物质与凝血因子XII（FXII）相互作用产生蛋白水解酶FXIIa时，血液凝固级联的内源性途径的接触活化开始。促凝血剂的表面性质被认为在活化中起重要作用。为了研究促凝血材料与血浆之间的相互作用机制，开发了一种形式和推导方式与Michaelis-Menten酶动力学相似的数学模型，以获得剂量（表面积和能量）与响应（凝血时间（CT））之间的易处理关系。将该模型应用于实验数据表明，CT取决于FXIIa浓度，并且可以使用线性依赖于接触时间的模型来分析产生的FXIIa的量。从这些实验和建模分析得出结论，凝血激活的主要机制涉及FXII通过促凝血剂表面的自激活或激肽释放酶介导的FXII的相互激活。FXIIa诱导的FXII自身扩增是不显著的。(c)2005爱思唯尔有限公司保留所有权利。
Contact activation of the intrinsic pathway of the blood coagulation cascade is initiated when a procoagulant material interacts with coagulation factor XII, (FXII) yielding a proteolytic enzyme FXIIa. Procoagulant surface properties are thought to play an important role in activation. To study the mechanism of interaction between procoagulant materials and blood plasma, a mathematical model that is similar in form and in derivation to Michaelis-Menten enzyme kinetics was developed in order to yield tractable relationships between dose (surface area and energy) and response (coagulation time (CT)). The application of this model to experimental data suggests that CT is dependent on the FXIIa concentration and that the amount of FXIIa generated can be analyzed using a model that is linearly dependent on contact time. It is concluded from these experiments and modeling analysis that the primary mechanism for activation of coagulation involves autoactivation of FXII by the procoagulant surface or kallikrein-mediated reciprocal activation of FXII. FXIIa-induced self-amplification of FXII is insignificant. (c) 2005 Elsevier Ltd. All rights reserved.