Validation of fractal dimension of the incipient blood clot in ST-segment-elevation myocardial infarction

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BackgroundMore than 200 combinations of antiplatelet and anticoagulant drugs can be given during an acute cardiac event. However, no biomarker is available to assess their global effect on clot formation and structure. Fractal dimension (Df) and clot formation time (TGP) are global markers of haemostasis that have been validated in healthy and anticoagulated blood. In contrast to standard coagulation assays, these biomarkers use unadulterated whole blood and are measured immediately at the bedside. Df quantifies clot microstructure whereas TGP is a real-time measure of clotting time, and both are calculated from the gel point (GP). We aimed to validate Df and TGP in ST-segment-elevation myocardial infarction (STEMI) and assess the effect of therapeutic intervention. MethodsWe recruited prospectively patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Venous blood samples were collected on admission (after 300 mg of aspirin), after PCI (after clopidogrel, heparin, and bivalirudin), and 24 h after admission. In addition to assessment of Df and TGP, each sample was assessed by standard coagulation tests and a full blood count. Wilcoxon signed-rank and paired t tests were used to compare changes from admission to after PCI and at 24 h. Spearman's correlation analysis was done to explore any associations. Normality was assessed with the Shapiro-Wilks test. This study was approved by the local Research Ethics Committee (REC Number 07/WMW02/34) and written informed consent was obtained from all participants. Findings33 patients (mean age 69 years [SD 12]; 19 men, 14 women) were included. Df on admission (mean 1·75, SD 0·05) was higher than values we have previously reported in healthy individuals despite use of antiplatelet therapy. Df after PCI was significantly lower than Df on admission (mean 1·64 [SD 0·06] vs 1·75 [0·05], p<0·0001) whereas Df at 24 h was similar to that on admission. TGP was significantly prolonged at after-PCI measurement compared with admission (median 723 s [IQR 492–1793] vs 210 [173–314], p<0·0001). Df correlated negatively with TGP (r=−0·75, p<0·0001), prothrombin time (r=−0·49, p<0·001), and partial thromboplastin time (r=−0·52, p<0·0001) but positively with fibrinogen (r=0·36, p=0·0009). There was no significant correlation observed between Df and platelets or haematocrit. InterpretationTherapeutic manipulation in STEMI especially with drugs given during PCI had a striking effect on clot structure and rate of coagulation as measured by Df and TGP. Larger studies are in progress to evaluate potential therapeutic strategies based on these biomarkers and their accuracy in detecting hypocoagulable and hypercoagulable states, and predicting cardiovascular risk. FundingNational Institute for Social Care and Health Research, Engineering and Physical Sciences Research Council.