Arterial thrombus formation

 

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Summary

Platelet and coagulation factor-dependent thrombus formation is critical to limit post-traumatic blood loss at sites of vascular injury. However, under pathological conditions like rupture of an atherosclerotic plaque, it may also lead to vessel occlusion causing myocardial infarction or stroke. Therefore, antithrombotic treatment is the prime therapeutic option in the prophylaxis and treatment of ischaemic cardio- and cerebrovascular diseases. The use of existing antithrombotic agents is, however, limited by their inherent effect on primary haemostasis. In recent years, major advances have been made in understanding the mechanisms of thrombus formation in haemostasis and thrombosis and some studies raised the interesting possibility that occlusive thrombus formation and haemo stasis may involve partially different mechanisms. This review briefly summarizes these developments and highlights newly identified mechanisms involved in platelet adhesion and activation, intracellular calcium signaling, integrin activation and initiation of coagulation. The suitability of these pathways as novel targets for antithrombotic therapy is discussed.

Zusammenfassung

Thrombozyten- und Koagulationsfaktor-abhängige Thrombusbildung ist essenziell um Blutungen nach einer Gefäßverletzung zu stoppen. Unter pathologischen Bedingungen hingegen, wie beispielsweise der Ruptur einer atherosklerotischen Plaque, kann sie auch zu einem Gefäßverschluss und damit zu Herzinfarkt oder Schlaganfall führen. Daher stellen antithrombotische Wirkstoffe die erste therapeutische Wahl in der Prophylaxe und Behandlung von ischämischen kardio- und zerebrovaskulären Erkrankungen dar. Die Anwendung existierender antithrombotischer Arzneimittel ist allerdings durch deren gleichzeitige Wirkung auf die primäre Hämostase begrenzt. In den letzten Jahren wurden große Fortschritte im Verständnis der Mechanismen der Thrombusbildung in Hämostase und Thrombose erzielt. Einige Studien deuten darauf hin, dass okklusiver Thrombusbildung und Hämostase teilweise unterschiedliche Mechanismen zu Grunde liegen. Dieser Übersichtsartikel fasst kurz diese Entwicklungen zusammen und hebt neu identifizierte Mechanismen der Thrombozyten-adhäsion und –aktivierung, den intrazellulären Kalzium-Signalwegen, der Integrinaktivierung, sowie dem Einsetzen der Koagulation hervor. Die Eignung dieser Signalwege als Angriffspunkte für eine antithrombotische Therapie wird ebenfalls diskutiert.

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