Analysis of platelet function and dysfunction

Summary

Although platelets act as central players of haemostasis only their cross-talk with other blood cells, plasma factors and the vascular compartment enables the formation of a stable thrombus. Multiple activation processes and complex signalling networks are responsible for appropriate platelet function. Thus, a variety of platelet function tests are available for platelet research and diagnosis of platelet dysfunction. However, universal platelet function tests that are sensitive to all platelet function defects do not exist and therefore diagnostic algorithms for suspected platelet function disorders are still recommended in clinical practice.

Based on the current knowledge of human platelet activation this review evaluates point-of-care related screening tests in comparison with specific platelet function assays and focuses on their diagnostic utility in relation to severity of platelet dysfunction. Further, systems biology-based platelet function methods that integrate global and specific analysis of platelet vessel wall interaction (advanced flow chamber devices) and posttranslational modifications (platelet proteomics) are presented and their diagnostic potential is addressed.

Zusammenfassung

Thrombozyten steuern zentral die Hämostase, aber erst ihr „cross-talk” mit anderen Blutzellen, Plasmafaktoren und dem vaskulären Kompartiment ermöglicht die Bildung eines stabilen Thrombus. Multiple Aktivierungsprozesse sowie komplexe Signalnetzwerke sind für eine normale Thrombozytenfunktion essenziell. Entsprechend existieren vielfältige Thrombozyten- Funktionstests für die Erforschung und Diagnose von Thrombozyten-Funktionsstörungen. Bisher konnten keine universellen Thrombozyten- Funktionstests entwickelt werden, die eine umfassende Detektion von Thrombozyten-Defekten gewährleisten. Daher werden diagnostische Algorithmen bei Verdacht auf Thrombozyten- Funktionsstörung in der klinischen Routine angewendet.

Diese Übersicht evaluiert basierend auf dem aktuellen Verständnis der Aktivierung und Funktion humaner Thrombozyten Point-ofcare- bezogene Screenings im Vergleich zu spezifischen Thrombozyten-Funktionsstests und gibt eine Übersicht über deren diagnostischen Anwendbarkeit bezüglich des Schweregrads der Thrombozyten-Dysfunktion. Dar - über hinaus werden Systembiologie-basierte Methoden und ihr diagnostisches Potenzial vorgestellt, die eine Integration von globalen und spezifischen Analysen der Thrombozyten- Wechselwirkung mit der Gefäßwand (moderne Flusskammersysteme) bzw. Der posttranslationalen Veränderungen von Thrombozytenproteinen (quantitative Proteomanalyse) verfolgen.

Keywords

Platelet function - platelet physiology - platelet pathology - point-of-care testing - thrombin - proteomics

Schlüsselwörter

Thrombozytenfunktion - Thrombozyten- Physiologie - Thrombozyten-Pathologie - Pointof- care-Test - Thrombin - Proteomanalyse

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