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

好的血块？

• 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

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.

心血管疾病及相关的血栓性疾病导致严重的发病率和死亡率，全世界每年有1710万人丧生。心血管疾病(包括心脏病和中风)约占英国死亡人数的十分之四。心血管疾病的发病率随着年龄的增长而显著增加，在社会贫困地区往往更高。在CVD中，内皮和血管损伤的过程以及凝血级联的激活导致异常凝块，通常伴随着过度的交联化的纤维蛋白网络。这种凝块通常被临床医生称为不良凝块。有人声称，更紧密的纤维蛋白网络会导致身体有效消化这些凝块的能力下降(溶解)。然而，全血凝块微结构和溶解之间的关系仍然存在争议。这在一定程度上是由于缺乏流变学技术来表征凝块的微观结构和适当地测量凝块溶解。表征血栓微结构和测量血栓溶解的能力将构成一种新的血液流变学设备的基础，该设备可用于诊断疾病状态(如CVD)、监测抗凝治疗、指导治疗干预和评估各种药物的有效性。该应用将解决这样的假设，即对早期血栓微结构的测量可以为新的血栓溶解生物标记物提供基础。人们普遍认为，早期的血栓微结构是随后血栓形成的模板，因此最终将控制用于溶解血栓的纤溶剂的可及性。计划通过在全血凝固过程中进行适当的流变学测量来检验这一假说。然而，由于凝块溶解的测量与血小板介导的凝块回缩同时存在，这使得凝块溶解的测量变得复杂，后者具有凝块从流变仪的测量板上拉出的效果。这项工作的一个新方面是对全血凝块进行粘弹性测量，同时保持流变仪测量板之间的零法向力。这具有预期的效果，即在凝块回缩期间，纤维蛋白网络起到将平板相互拉动的作用，从而便于对收缩的凝块进行适当的粘弹性测量。这些测量将使我们更好地了解凝块微观结构和凝块溶解之间的关系。总体而言，这项研究的最终目标是开发一种新的血液流变学工具，它有可能用于临床环境中，造福于患者。

项目成果

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
• 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

• 发表时间: 2013
• 作者: Badiei N

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

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