Primary haemostasis and its assessment by laboratory tests

Summary

Platelets constantly patrol the inner surface of blood vessels searching leaks to be sealed, in order to prevent blood loss. When they detect a vessel injury their action can be divided into three phases. Adhesion: The platelets adhere to the injured blood vessel wall via their receptors glycoprotein (GP) Ib and integrin α2bβ3 (GPIIb/IIIa) mediated by the ligands von Willebrand factor (VWF), fibrinogen and others. Aggregation: Platelets stick to each other through fibrinogen bridging integrin α2bβ3 (GPIIb/IIIa) on adjacent platelets. Secretion: During activation the content of platelet granules is released by exocytosis, thus augmenting and propagating formation of a haemostatic plug or thrombus.

Laboratory tests mimic one or several aspects of these three phases to obtain reliable data on a patients platelet function. In this overview assays, test principles, and pitfalls are presented.

Zusammenfassung

Thrombozyten patrouillieren ständig die innere Oberfläche der Blutgefäße auf der Suche nach Lecks, um drohenden Blutverlust zu verhindern. Entdecken sie eine Gefäßverletzung treten sie in Aktion. Man kann dabei drei Phasen unterscheiden: Adhäsion: Die Thrombozyten haften an der verletzten Gefäßwand durch ihre Rezeptoren Glykoprotein (GP) Ib und Integrin α2bβ3 (GPIIb/IIIa), die an den Liganden von Willebrand Faktor (VWF), Fibrinogen und anderen binden. Aggregation: Thrombozyten haften aneinander durch Fibrinogen, das die Integrin α2bβ3 Rezeptoren benachbarter Plättchen miteinander verbindet. Sekretion: Plättchenaktivierung führt zur Exozytose thrombozytärer Granula und Freisetzung des Granulainhaltes. Dadurch wird die Bildung eines hämostatischen Verschlusses oder Thrombus gesteigert und vermehrt. Labor-Tests bilden einen oder mehrere Aspekte dieser drei Phasen nach, um verlässliche Daten zur Thrombozytenfunktion zu erhalten. Diese Übersicht präsentiert Testverfahren, Testprinzipien und Fallstricke.

Keywords

Platelets - adhesion - aggregation - von Willebrand factor

Schlüsselwörter

Thrombozyten - Adhäsion - Aggregation - von-Willebrand- Faktor

• References

• 1 Savage B, Ginsberg MH, Ruggeri ZM. Influence of fibrillar collagen structure on the mechanisms of platelet thrombus formation under flow. Blood 1999; 94: 2704-15.
• 2 Butenas S, Branda RF, vanဩt Veer C. et al. Platelets and phospholipids in tissue factor-initiated thrombin generation. Thromb Haemost 2001; 86: 660-7.
• 3 Ruggeri ZM, Saldivar E. Platelets, Hemostasis and Thrombosis. In: Ruggeri ZM. (ed). Von Willebrand factor and the mechanisms of platelet function. Berlin Heidelberg: Springer; 1998: 7-8.
• 4 Livio M, Gotti E, Marchesi D. et al. Uraemic bleeding: role of anaemia and beneficial effect of red cell transfusions. Lancet 1982; 2: 1013-5.
• 5 Karnis A, Goldsmith HL, Mason SG. Axial migration of particles in Poiseuille flow. Nature 1963; 200: 159-60.
• 6 Goldsmith HL, Turitto VT. Rheological aspects of thrombosis and haemostasis: Basic principles and applications. ICTH-report – subcommittee on rheology of the International Committee on Thrombosis and Haemostasis. Thromb Haemost 1986; 55: 415-35.
• 7 Goldsmith HL, Cokelet G, Gaehtgens P. et al. Evolution of his concepts cardiovascular physiology. Am J Physiol 1989; 257: H1005-15.
• 8 Slichter SJ, Harker LA. Thrombocytopenia: mechanisms and management of defects in platelet production. Clin Haematol 1978; 7: 523-39.
• 9 Refaai MA, Laposata M. Platelet count. In: Michelson AD. (ed). Platelets. San Diego: Academic Press; 2002: 279-82.
• 10 Lind SE. Bleeding time. In: Michelson AD. (ed). Platelets. San Diego: Academic Press; 2002: 283-9.
• 11 Barthels M, von Depka M. Das Gerinnungskompendium. Stuttgart: Thieme; 2003
• 12 Cattaneo M, Federici AB, Lecchi A. et al. Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease. Thromb Haemost 1999; 82: 35-9.
• 13 Domsch Ch, Müller-Beißenhirtz H, Spannagl M. Einsatz des PFA-100 bei angeborenen und errworbenen hämorrhagischen Diathesen. Hämostaseologie 1999; 19: 176-81.
• 14 Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-9.
• 15 Refaai MA, Laposata M. Platelet aggregation. In: Michelson AD. (ed). Platelets. San Diego: Academic Press; 2002: 291-6.
• 16 Schneppenheim R, Budde U. Classification of von Willebrand disease. Hämostaseologie 2004; 24: 27-36.
• 17 Ruggeri ZM. Type IIB von Willebrand disease: a paradox explains how von Willebrand factor works. J Thromb Haemost 2004; 2: 2-6.
• 18 Michelson AD, Barnard MR, Krueger LA. et al. Flow cytometry. In: Michelson AD. (ed). Platelets. San Diego: Academic Press; 2002: 297-315.
• 19 Steinhubl SR, Kereiakes DJ. Ultegra Rapid Platelet Function Analyzer. In: Michelson AD. (ed). Platelets. San Diego: Academic Press; 2002: 317-23.
• 20 Francis JL. Platelet Function Analyzer (PFA)-100. In: Michelson AD. (ed). Platelets. San Diego: Academic Press; 2002: 325-35.
• 21 Varon D, Savion N. Cone and Plate(let) Analyzer. In: Michelson AD. (ed). Platelets. San Diego: Academic Press; 2002: 337-45.