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

<p>Abstract</p> <p>Background</p> <p>Cardiovascular 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 sub...

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Main Authors: Bratseth Vibeke, Pettersen Alf-Åge, Opstad Trine B, Arnesen Harald, Seljeflot Ingebjørg
Format: Article
Language:English
Published: BMC 2012-08-01
Series:Thrombosis Journal
Subjects:
Online Access:http://www.thrombosisjournal.com/content/10/1/12
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author Bratseth Vibeke
Pettersen Alf-Åge
Opstad Trine B
Arnesen Harald
Seljeflot Ingebjørg
author_facet Bratseth Vibeke
Pettersen Alf-Åge
Opstad Trine B
Arnesen Harald
Seljeflot Ingebjørg
author_sort Bratseth Vibeke
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Cardiovascular 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.</p> <p>Methods</p> <p>Venous 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.</p> <p>Results</p> <p>We 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).</p> <p>Conclusions</p> <p>In 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 <url>http://www.clinicaltrials.gov</url>: NCT00222261.</p>
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spelling doaj.art-34c69a2fe82c4b01b2911ee63c2c5bce2022-12-21T23:41:37ZengBMCThrombosis Journal1477-95602012-08-011011210.1186/1477-9560-10-12Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatmentBratseth VibekePettersen Alf-ÅgeOpstad Trine BArnesen HaraldSeljeflot Ingebjørg<p>Abstract</p> <p>Background</p> <p>Cardiovascular 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.</p> <p>Methods</p> <p>Venous 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.</p> <p>Results</p> <p>We 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).</p> <p>Conclusions</p> <p>In 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 <url>http://www.clinicaltrials.gov</url>: NCT00222261.</p>http://www.thrombosisjournal.com/content/10/1/12Thrombin generationCoronary artery diseaseHypercoagulabilityProthrombotic markersThe CAT assayEndogenous thrombin potentialeAntiplatelet treatmentAspirinClopidogrel
spellingShingle Bratseth Vibeke
Pettersen Alf-Åge
Opstad Trine B
Arnesen Harald
Seljeflot Ingebjørg
Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment
Thrombosis Journal
Thrombin generation
Coronary artery disease
Hypercoagulability
Prothrombotic markers
The CAT assay
Endogenous thrombin potentiale
Antiplatelet treatment
Aspirin
Clopidogrel
title Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment
title_full Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment
title_fullStr Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment
title_full_unstemmed Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment
title_short Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment
title_sort markers of hypercoagulability in cad patients effects of single aspirin and clopidogrel treatment
topic Thrombin generation
Coronary artery disease
Hypercoagulability
Prothrombotic markers
The CAT assay
Endogenous thrombin potentiale
Antiplatelet treatment
Aspirin
Clopidogrel
url http://www.thrombosisjournal.com/content/10/1/12
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