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OVERVIEW OF HEMOSTASIS

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PRIMARY HEMOSTASIS

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Hemostasis, which may be defined as the process by which blood loss at sites of blood vessel disruption is mitigated and ultimately stopped, requires a complex and coordinated interplay of factors. The activity of platelets at the site of vascular injury constitutes primary hemostasis. Initially, platelets are exposed to collagen, fibronectin, and other molecules in the subendothelial matrix at the site of vascular injury, leading to their adherence, activation, and aggregation; the accumulated platelet mass then may span the break. von Willebrand factor (vWF) assists platelets in adherence to the site of endothelial injury especially in high-shear conditions, such as those found in arterioles. Following release from storage sites in the endothelium, vWF binds to its receptors on the platelet membrane, tethering them to the site of the vascular damage. vWF also bridges platelets to one another.

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SECONDARY HEMOSTASIS

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The activity of coagulation factors at the site of endothelial injury leading to conversion of plasma fibrinogen to a fibrin clot constitutes secondary hemostasis. Platelets that are present at the site of a vascular break provide a phospholipid surface on which coagulation factor complexes may assemble and donate tissue factor (TF), which activates coagulation. The activation of platelets also leads to release of a variety of pro-coagulant molecules, including thrombin. The tissue injury pathway of coagulation entails the conversion of factor X to factor Xa by activated factor VII in the presence of TF. Factor Xa then binds factor Va in the presence of phospholipid and calcium, forming the prothrombinase complex, which then converts factor II to factor IIa (thrombin). The common pathway involves the cleavage of factor II by prothrombinase to yield thrombin, and thrombin cleavage of fibrinogen to form fibrin, which is then cross-linked via the action of factor XIIIa. The contact pathway of coagulation begins with the activation of contact factors (kallikrein, XII, others), leading serially to formation of factors XIa and IXa; the tenase complex (factors IXa, VIIIa, and X, in the presence of phospholipid and calcium) converts factor X to factor Xa, which leads to formation of thrombin and cleavage of fibrinogen (as above).

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In vivo, the tissue injury pathway usually comprises the initial activation of coagulation, then activates the contact system through thrombin-mediated activation of factor XI. Excessive activation of coagulation is mitigated by the activity of endogenous proteins such as proteins C and S (which decrease the activity of factor V), thrombomodulin (via a negative feedback mechanism), and the plasminogenplasmin system, which leads to fibrinolysis.

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Fogarty  PF  et al.. Disorders of Hemostasis I: Coagulation. In: Rodgers  GP, editors  et al.. The Bethesda Handbook of Clinical Hematology, 3rd ed. Philadelphia: Lippincott Williams and Wilkins, 2013.

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INTRODUCTION

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In assessing patients for defects of hemostasis, the clinical context must be considered carefully (Table 14–1). Heritable ...

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