The Cell-Based Coagulation Model
Hemostasis has traditionally been divided into primary and secondary hemostasis. In primary hemostasis, once subendothelial collagen is exposed to blood by vascular injury, von Willebrand factor (vWF) binds to collagen and platelets to form vWF-platelet c
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The Cell-Based Coagulation Model Christoph Sucker and Rainer B. Zotz
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Introduction
The term “hemostasis” summarizes a variety of physiological processes that lead to a cessation of bleeding in case of vascular injury. Hemostasis keeps blood within damaged blood vessels and is therefore a life-saving mechanism. Furthermore, adequate hemostasis is a prerequisite for effective wound healing following injury. The process of hemostasis is complex. In the initial phase, constriction of injured blood vessels leads to a reduction of blood flow. Then a plug forms, consisting of adhering and aggregating platelets and fibrin; this leads to a complete control of blood loss and allows for the repair of the vascular and tissue defect. Since antiquity, physicians have been developing and extending theories to explain the process of coagulation. Some of the most important steps on this journey were the description of fibrin as the main content of blood clots, by Johannes Mueller (1801–1858); the description of its precursor, fibrinogen, by Rudolf Virchow (1821–1902); and its isolation by Prosper Sylvain Denis (1799–1863). Alexander Schmidt (1831–1894) and Rudolf Virchow were the first to suggest that the formation of fibrin from fibrinogen is an enzymatic process. Alexander Schmidt termed the fibrinogen-converting enzyme “thrombin” and its precursor “prothrombin” (Schmidt 1872, 1892). In 1890, calcium was found to be essential for coagulation
C. Sucker LaboMed Gerinnungszentrum Berlin, Tauentzienstrasse 7 b/c, Berlin 10789, Germany e-mail: [email protected] R.B. Zotz (*) Centrum für Blutgerinnungsstörungen und Transfusionsmedizin (CBT), Immermannstrasse 65 a, Düsseldorf 40210, Germany e-mail: [email protected]
C.E. Marcucci, P. Schoettker (eds.), Perioperative Hemostasis, DOI 10.1007/978-3-642-55004-1_1, © Springer-Verlag Berlin Heidelberg 2015
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C. Sucker and R.B. Zotz
(Arthus and Pagès 1890). Platelets were discovered in 1865 and described further in the following years (Brewer 2006). Paul Morawitz (1879–1936) published his classic theory of plasmatic hemostasis just over 100 years ago. According to his model, prothrombin is converted to thrombin by tissue-derived thrombokinase; thrombin then converts fibrinogen to fibrin – the most important step of coagulation (Morawitz 1905). This first concept of hemostasis was modified and extended over the following years. In particular, more coagulation factors were discovered, allowing for the development of more detailed concepts of the hemostatic process (Wright 1962; Douglas 1999). This resulted in the publication of the “Cascade Model” by MacFarlane and the “Waterfall Sequence Model” of plasmatic hemostasis by Davie and Ratnoff (MacFarlane 1964; Davie and Ratnoff 1964). In the following sections, we illustrate the process of primary hemostasis, defined as all aspects of platelet adhesion and platelet aggregation, and secondary hemostasis, defined as the process of fibrin formation and fibrin stabilization. In the final section, we briefly review the most important an
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