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Thrombosis and disabilities

Objectif

The European Concerted Action on Thrombosis and Disabilities (ECAT) is a collaborative multicentre effort to elucidate the role of thrombotic processes in the pathogenesis of various arterial and venous vessel diseases.

The major activities of the ECAT are focused on finding laboratory assays which are able to predict which persons are at risk of suffering thrombosis. If such assays are available, more insight into the pathogenetic mechanisms of thrombosis may be obtained, individuals at high risk may be identified and, ultimately, effective measures can be developed for intervention on high-risk patients. The assays being tested are based on factors playing a role in processes underlying thrombosis: these factors are derived from vascular endothelium, blood platelets, the coagulation and fibrinolysis systems. Prediction of thrombotic events by assays presupposes the existence of a prethrombotic state in the blood circulation.
A European study has been set up to elucidate the role of thrombotic processes in the pathogenesis of various arterial and venous vessel diseases. This involved analysis of the results of haemostasis assays for important in thrombus formation, and correlation to subsequent clinical events. It was found that patients at risk of a coronary event had increased levels of the haemostatic fators fibrinogen and von Willebrand factor (vWF) and a depressed fibrinolytic activity, mainly indicated by increased t-plasminogen activator (t-PA) antigen which is linked to low t-PA activity. Also patients with blood group A and B are more prone to coronary events than blood group O which may be explained by the occurrence of blood group A and B structures in the vWF, indicating a genetic determinant.
The acute phase protein C-reactive protein (CRP) was increased in patients at risk of a coronary event, but remained below concentrations of 10 mg/l. This important finding show that CRP is a sensitive marker to follow the progression of atherosclerosis. It explains partially the increase of levels of fibrinogen, which is known to be an acute phase reactant. It also explains previously reported risk indicators of a myocardial infarction such as increased erythrocyte sedimentation rate (ESR) and increased white blood cell count.
Results obtained with coronary angiography support the role of fibrinogen in the progression of atherosclerosis in that patients with stenoses had higher levels of this factor.
The assays indicated the risk independent of other, known risk factors. They do not correlate with total cholesterol in plasma, which was only weakly predictive for a myocardial infarction in patients with angina pectoris.
It is suggested that risk scores for patients with angina pectoris should now incorporate the levels of fibrinogen, vWF and t-PA antigen.

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TNO Gaubius Institute
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PO Box 430
2300 AK Leiden
Pays-Bas

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