Good clot? Bad clot? Rheological and microstructural studies of abnormal blood clots from incipiency to breakdown

好的血块？

基本信息

批准号：
EP/I019405/1
负责人：
Karl Hawkins
金额：
$ 12.97万
依托单位：
Swansea University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2011
资助国家：
英国
起止时间：
2011 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FI019405%2F1
关键词：
Good clot Bad Rheological microstructural

项目摘要

Cardiovascular disease (CVD) and associated thrombotic disorders cause significant morbidity and mortality claiming 17.1 Million lives a year worldwide. CVD (including heart disease and stroke) accounts for around four out of ten of deaths in the UK. The incidence of CVD increases markedly with age and is often higher in socially deprived areas. In CVD, the processes of endothelial and vascular damage and activation of the coagulation cascade result in abnormal clots, often with excessively cross-linked fibrin networks. Such clots are often referred to as bad clots by the clinician. It has been claimed that tighter fibrin networks lead to a decreased ability of the body to effectively digest these clots (lysis). However, the relationships between whole blood clot microstructure and lysis remains contentious. This is in part due to the lack of rheological techniques to characterise clot microstructure and to appropriately measure clot lysis. The ability to characterise clot microstructure and measure clot lysis will form the basis of a new haemorheometrical device which can be used to diagnose disease states (such as CVD), to monitor anticoagulant therapy, to guide therapeutic interventions and to assess the efficiency of various drugs.This Application will address the hypothesis that measurement of incipient clot microstructure can provide the basis for a new biomarker of clot lysis. It is widely assumed that the incipient clot microstructure is a template for ensuing clot development, and will therefore ultimately control the accessibility of fibrinolytic agents that serve to lyse the clot. It is planned to test this hypothesis by conducting appropriate rheological measurements during whole blood coagulation. However, measurement of clot lysis has been complicated by the fact that it exists simultaneously with platelet mediated clot retraction which has the effect of the clot pulling away from the rheometer's measuring plates. A novel aspect of this work is to perform viscoelastic measurements of whole blood clots whilst maintaining a zero normal force between the rheometer's measuring plates. This has the desired effect that, during clot retraction, the fibrin network acts to pull the plates towards each other therefore facilitating appropriate viscoelastic measurements of the contracted clot. These measurements will allow a greater understanding of the relationships between clot microstructures and clot lysis. Overall, the ultimate goal of the research is to develop a new haemorheometrical tool which has the potential to be used in a clinical setting for patient benefit.

心血管疾病（CVD）和相关的血栓性疾病会导致全球一年一年生命1,710万人的死亡率和死亡率显着。在英国，CVD（包括心脏病和中风）约为十分之四。 CVD的发病率随着年龄的增长而明显增加，在社会贫困地区通常会更高。在CVD中，内皮和血管损伤的过程以及凝血级联反应的激活导致异常凝块，通常具有过度交联的纤维蛋白网络。临床医生通常将这种凝块称为坏凝块。据称，更紧密的纤维蛋白网络导致人体有效消化这些凝块的能力降低（裂解）。但是，全血凝块微观结构和裂解之间的关系仍然存在争议。这部分是由于缺乏表征凝块微观结构并适当测量凝块裂解的流变学技术。表征凝块微观结构和测量凝块裂解的能力将构成一种新的血液计量仪，可用于诊断疾病状态（例如CVD），以监测抗凝治疗，以指导治疗性干预措施并评估各种药物的效率此应用将解决以下假设：初始凝块微观结构的测量可以为新的凝块溶解生物标志物提供基础。广泛认为，初始的凝块微观结构是用于随之而来的凝块开发的模板，因此最终将控制用于凝固凝块的纤维蛋白水解剂的可访问性。计划通过在全血凝结过程中进行适当的流变学测量来检验这一假设。但是，凝块溶解的测量使它与血小板介导的凝块缩回同时存在的事实变得复杂，该凝块缩回的作用是凝块从流变仪的测量板中撤离的作用。这项工作的一个新方面是对全血凝块进行粘弹性测量，同时保持变句的测量板之间保持零正常力。这具有预期的效果，即在凝块缩回期间，纤维蛋白网络起作用可将板彼此拉动，从而促进合同的凝块的适当粘弹性测量。这些测量将使对凝块微观结构与凝块裂解之间的关系有更深入的了解。总体而言，该研究的最终目标是开发一种新的血液计量仪工具，该工具有可能在临床环境中用于患者益处。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The CentriMag centrifugal blood pump as a benchmark for in vitro testing of hemocompatibility in implantable ventricular assist devices.

DOI：
10.1111/aor.12351
发表时间：
2015-02
期刊：
Artificial organs
影响因子：
2.4
作者：
Chan CH;Pieper IL;Hambly R;Radley G;Jones A;Friedmann Y;Hawkins KM;Westaby S;Foster G;Thornton CA
通讯作者：
Thornton CA

Fractal discrimination of random fractal aggregates and its application in biomarker analysis for blood coagulation

随机分形聚集体的分形判别及其在凝血生物标志物分析中的应用

DOI：
10.1016/j.chaos.2012.04.004
发表时间：
2012
期刊：
Chaos, Solitons & Fractals
影响因子：
0
作者：
Brown M
通讯作者：
Brown M

Effects of shear flow on the microstructure and elasticity of incipient clots in whole blood and fibrin-thrombin gels

剪切流对全血和纤维蛋白-凝血酶凝胶中初期凝块的微观结构和弹性的影响

DOI：
发表时间：
2013
期刊：
影响因子：
0
作者：
Badiei N
通讯作者：
Badiei N

Reevaluation of the Harboe Assay as a Standardized Method of Assessment for the Hemolytic Performance of Ventricular Assist Devices

DOI：
10.1111/j.1525-1594.2012.01515.x
发表时间：
2012-08-01
期刊：
ARTIFICIAL ORGANS
影响因子：
2.4
作者：
Chan, Chris H. H.;Hilton, Andrew;Hawkins, Karl
通讯作者：
Hawkins, Karl

Effects of unidirectional flow shear stresses on the formation, fractal microstructure and rigidity of incipient whole blood clots and fibrin gels.

DOI：
10.3233/ch-151924
发表时间：
2015
期刊：
Clinical hemorheology and microcirculation
影响因子：
2.1
作者：
Badiei N;Sowedan AM;Curtis DJ;Brown MR;Lawrence MJ;Campbell AI;Sabra A;Evans PA;Weisel JW;Chernysh IN;Nagaswami C;Williams PR;Hawkins K
通讯作者：
Hawkins K