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[Atheroma and antithrombotic agents]
1Laboratoire d'hématologie, CHU Timone, Marseille.
Insights
Clotting factors and platelets contribute to atherothrombosis and lesion progression. Therapies targeting these factors show promise in preventing occlusive events and vessel wall damage.
Area of Science:
- Cardiovascular Science
- Hematology
- Pharmacology
Context:
- Atherothrombosis involves clotting factors and platelets in thrombus formation and lesion progression.
- Platelets release growth factors, stimulating smooth muscle cell proliferation.
- Therapeutic trials have explored platelet-inhibiting drugs for occlusive events.
Purpose:
- To review the role of clotting factors and platelet activity in atherothrombosis.
- To assess the efficacy of antiplatelet agents and anticoagulants in preventing vascular lesions.
- To highlight emerging therapeutic strategies targeting coagulation and fibrinolysis.
Summary:
- Clotting factors and activated platelets are implicated in atherothrombosis, thrombus formation, and vascular lesion development.
- Platelet anti-aggregants have shown efficacy in preventing occlusive events, but their role in preventing vessel wall lesions is less clear.
- Elevated plasma levels of fibrinogen, factor VII, and plasminogen activator inhibitor-1 (PAI-1) are coronary risk markers.
- Ongoing trials investigate vitamin K antagonists and metformin for their preventive effects on atherothrombosis.
- Some antiplatelet and lipid-lowering drugs may reduce levels of fibrinogen, factor VII, and PAI-1.
Impact:
- Understanding the multifaceted role of hemostatic factors in atherothrombosis is crucial for developing targeted therapies.
- Identifying effective treatments for preventing both occlusive events and the progression of vascular lesions can improve patient outcomes.
- The results of ongoing therapeutic trials are anticipated to guide future clinical practice in managing cardiovascular risk.
Abstract:
The clotting factors are thought to play a part in the development of atherothrombosis, not only in the formation of occlusive thrombosis but also in the progression of vessel wall lesions. Activated platelets participate in thrombus formation and stimulate the proliferation of smooth muscle cells via the growth factor that they liberate. Many therapeutic trials have been carried out with different platelet-inhibiting drugs and some have show a preventive effect on occlusive events. The role of platelet anti-aggregants in the prevention of vessel wall lesions is more difficult to demonstrate. Activation of the coagulation system or a defect in the fibrinolytic system result in the accumulation of intravascular and intraparietal fibrin. The increases in plasma concentration of factors such as the fibrinogen, factor VII, a fibrinolytic inhibitor, PAI-1, are considered to be markers of coronary risk. The preventive effect of low-dose vitamin K antagonists which reduce factor VII activity and the effect of metformin which counteracts insulin resistance and reduces PAI-1 concentrations, are at present under trial. Some platelet antiaggregants and lipid lowering drugs reduce fibrinogen, factor VII and PAI-1 concentrations. Results of therapeutic trials of these molecules are eagerly awaited.