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Thromb Haemost 2006; 96(06): 738-743
DOI: 10.1160/TH06-08-0451
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Effect of antiplatelet agents clopidogrel, aspirin, and cilostazol on circulating tissue factor procoagulant activity in patients with peripheral arterial disease

A. Koneti Rao
1   The Sol Sherry Thrombosis Research Center and Section of Hematology, Department of Medicine
,
Vijender R. Vaidyula
1   The Sol Sherry Thrombosis Research Center and Section of Hematology, Department of Medicine
,
Shagun Bagga
1   The Sol Sherry Thrombosis Research Center and Section of Hematology, Department of Medicine
,
Gauthami Jalagadugula
1   The Sol Sherry Thrombosis Research Center and Section of Hematology, Department of Medicine
,
John Gaughan
2   Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
,
Douglas B. Wilhite
3   Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
,
Anthony J. Comerota
4   Jobst Vascular Center, Toledo, Ohio, USA
› Author AffiliationsFinancial support: These studies were supported by a grant from Otsuka Pharmaceutical, Inc.
Further Information

Publication History

Received 17 August 2006

Accepted after resubmission 20 October 2006

Publication Date:
29 November 2017 (online)

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Summary

Tissue factor (TF) is the physiological initiating mechanism for blood coagulation. Platelets play an important role in monocyte TF expression, thrombosis and inflammation. Aspirin, clopidogrel and cilostazol, which inhibit platelet responses by different mechanisms, are widely used in patients with arterial diseases. We tested the hypothesis that platelet-inhibiting agents inhibit the levels of circulatingTF procoagulant activity (TF-PCA) in patients with peripheral arterial disease (PAD).Twenty-six patients with lower extremity PAD, average age 65.9 ± 8.4 years (mean± SEM), were studied at baseline and following sequential twoweek treatment regimens with aspirin (325 mg daily), clopidogrel (75 mg daily) or a phosphodiesterase inhibitor cilostazol (100 mg twice daily) singly, and with each possible combination of these agents. Circulating TF-PCA in whole blood, and plasma factor VIIa, prothrombin fragment F1.2, thrombin-antithrombin complexes (TAT), and P-selectin were measured. Baseline TFPCA levels in the patients were elevated (131 ± 19 U/ml) compared to control subjects (23 ± 2, p<0.0001).TF-PCA levels declined following treatment with clopidogrel alone, and with combinations of clopidogrel with aspirin or cilostazol, with the lowest levels being with the triple-drug combination. Plasma P-selectin declined in all treatment groups. No changes were noted in plasma factorVIIa, F1.2 or TAT.In conclusion, treatment of PAD patients with antiplatelet agents decreases circulatingTF, a molecule with prothrombotic and proinflammatory effects. These findings suggest an unrecognized mechanism, beyond inhibiting aggregation responses, for the efficacy of antiplatelet drugs in patients with arterial diseases.

Keywords

Aspirin - clopidogrel - tissue factor - peripheral vascular disease - platelets
 

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