Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment

Abstract

BackgroundCardiovascular disease with disturbances in the haemostatic system, might lead to thrombotic complications with clinical manifestations like acute myocardial infarction (AMI) and stroke. Activation of the coagulation cascade with subsequent increased thrombin generation, characterizes a prothrombotic phenotype. In the present study we investigated whether prothrombotic markers were associated with risk factors and clinical subgroups in a cohort of patients with angiographically verified coronary artery disease (CAD). The patients were randomized to long-term treatment with the antiplatelet drugs aspirin or clopidogrel, and we further investigated the effect on hypercoagulability of such treatment for 1 year, of which limited data exists.MethodsVenous blood samples were collected in fasting condition between 08:00 and 10:30 am, at baseline when all patients were on aspirin therapy (n = 1001) and in 276 patients after 1 year follow-up on aspirin or clopidogrel. In vivo thrombin generation was assessed by prothrombin fragment 1 + 2 (F1+2) and D-dimer, and the endogenous thrombin potentiale (ETP) in the calibrated automated thrombogram (CAT) assay, representing ex vivo thrombin generation. In addition soluble tissue factor (sTF) and free- and total tissue factor pathway inhibitor (TFPI) were measured.ResultsWe found age to be significantly associated with F1+2 and D-dimer (β = 0.229 and β =0.417 respectively, p <0.001, both). Otherwise, only weak associations were found. F1+2 and D-dimer were higher in women compared to men (p <0.001 and p = 0.033, respectively). Smokers had elevated levels of ETP compared to non-smokers (p = 0.014). Additionally, patients on renin-angiotensin system (RAS) inhibition showed significantly higher levels of F1+2, compared to non-users (p = 0.013). Both aspirin and clopidogrel reduced levels of ETP after 12 months intervention (p = 0.003 and p <0.001, respectively) and the levels of F1+2 were significantly more reduced on aspirin compared to clopidogrel (p = 0.023).ConclusionsIn the present population of stable CAD, we could demonstrate a more hypercoagulable profile among women, smokers and patients on RAS medication, assessed by the prothrombotic markers F1+2, D-dimer and ETP. Long-term antiplatelet treatment with aspirin alone seems to attenuate thrombin generation to a greater extent than with clopidogrel alone. The study is registered at http://www.clinicaltrials.gov: NCT00222261.

Characterisation of clot microstructure properties in stable coronary artery disease

“…These results suggest that dual antiplatelet therapy is effective in mediating clot microstructure, where patients have lower values of d f corresponding to the production of less densely packed and more porous clots. 4 This study provides further evidence of the potential of d f in monitoring the effects of antiplatelet therapy on clot microstructure formation. 11 The limitations of this study include discrepancy in the numbers collected for both groups.…”

“…[1][2][3][4] While CAD has been linked to an increased prothrombotic state, no marker has been identified that can accurately assess abnormalities of global haemostasis due to this process and to severity of disease. Identifying a global haemostatic marker of coagulability and fibrinolysis may be important in stratifying risk of atherothrombosis and providing the basis for individualised therapeutic management.…”

Pathophysiologic Mechanisms of Cardiovascular Disease in Obstructive Sleep Apnea Syndrome

“…Hypercoagulability resulting from increased coagulation or inhibited fibrinolysis is associated with an increased risk for cardiovascular disease [81, 82]. This is another factor implicated in its association with OSAS [83, 84].…”

The genetic variation rs6903956 in the novel androgen-dependent tissue factor pathway inhibitor regulating protein (ADTRP) gene is not associated with levels of plasma coagulation factors in the Singaporean Chinese

“…Thrombin converts soluble fibrinogen to insoluble fibrin strands and form blood clots [9–11]. Previous studies have shown that coagulation factors have an essential role in advancing atherosclerosis and CAD [12–14]. High levels of FVII coagulant activity (FVIIc) and fibrinogen have been found to be significantly associated with increased risk of coronary events [15].…”