Characterisation of clot microstructure properties in stable coronary artery disease

Abstract

BackgroundCoronary artery disease (CAD) is associated with an increased prothrombotic tendency and is also linked to unfavourably altered clot microstructure. We have previously described a biomarker of clot microstructure (df) that is unfavourably altered in acute myocardial infarction. The df biomarker assesses whether the blood will form denser or looser microstructures when it clots. In this study we assessed in patients with stable chest pain whether df can differentiate between obstructed and unobstructed CAD.MethodsA blood sample prior to angiography was obtained from 251 consecutive patients undergoing diagnostic coronary angiography. Patients were categorised based on angiographic findings as presence or absence of obstructive CAD (stenosis ≥50%). The blood sample was assessed using the df biomarker, standard laboratory markers and platelet aggregometry (Multiplate).ResultsA significant difference (p=0.028) in df was observed between obstructive CAD (1.748±0.057, n=83) and unobstructive CAD (1.732±0.052, n=168), where patients with significant CAD produce denser, more tightly packed clots. df was also raised in men with obstructive CAD compared with women (1.745±0.055 vs 1.723±0.052, p=0.007). Additionally df significantly correlated with the platelets response to arachidonic acid as measured by the ASPItest area under the curve readings from platelet aggregometry (correlation coefficient=0.166, p=0.008), a low value of the ASPItest indicating effective aspirin use was associated with looser, less dense clots.ConclusionsFor the first time, we characterise clot microstructure, as measured by df, in patients with stable CAD. df can potentially be used to risk-stratify patients with stable CAD and assess the efficacy of therapeutic interventions by measuring changes in clot microstructure.

Detection of Exhaust Particulate Induced Blood Clotting Anomalies using Rheometric Techniques

“…However, once the ERIC procedure is applied, the 𝑑 𝑓 values indicate a slight increase from 3.4 x10 9 particles ml -1 , commensurate with literature for alternative pathologies (148,149). As seen in Figure 4-36, as the number of particles present in the gel samples increased, it appears that the 𝑡 𝑔𝑒𝑙 decreases, with an anomalous data point at 1.1 x10 9 particles ml -1 .…”

“…Obstructive coronary artery disease (CAD) also resulted in a significantly increased 𝑑 𝑓 value of 𝑑 𝑓 =1.748 ± 0.057 when clots were analysed rheologically (149).…”

“…These studies (54,143,148,149) used GP analysis to determine 𝑑 𝑓 which is linked to the stress relaxation characteristic of the incipient gel network through Muthukumar's Relation.…”

Does Exercise Influence the Susceptibility to Arterial Thrombosis? An Integrative Perspective

“…Fractal dimension provides a description of the incipient clot, which is the initial templating structure of the clot, which leads to its ongoing mechanical structure and strength ( Figure 1 ) ( Curtis et al, 2011 , 2013 ). Low values of fractal dimension are equivalent to a weak and less dense clot with low number of branches, whereas high values are equivalent to a strong and dense clot with a high number of complex structured branches, which is more difficult to break down therapeutically ( Evans et al, 2010 ; Sabra et al, 2017 ). In acute vascular inflammatory disease such as ischemic stroke and myocardial infarction, there is considerable over-production of mass and cross-linking at this templating phase, which leads to a very strong and abnormally structured clot, as compared to clot formation in healthy individuals ( Figures 1 , 2 ).…”

“…In acute vascular inflammatory disease such as ischemic stroke and myocardial infarction, there is considerable over-production of mass and cross-linking at this templating phase, which leads to a very strong and abnormally structured clot, as compared to clot formation in healthy individuals ( Figures 1 , 2 ). In contrast to standard and conventional coagulation measurements like PT or APTT, fractal dimension is performed in untreated blood within minutes after blood withdrawal and provides a rapid measurement of the integrated hemostatic property and thereby an immediate indication of the risk of cardiovascular events ( Sabra et al, 2017 ). Limitations include the requirement of relatively expensive equipment, and as with platelet aggregometry, the measurement is made in vitro without physiological hemodynamic impact.…”