Sarah Bos

10 CHAPTER 1 Hemostasis Hemostasis is a process to prevent and stop bleeding. It is a complex balance in which damage to the endothelium is managed and normal flow through the vessels is maintained. The interplay between the endothelium of the vessel wall, platelets, coagulation, and the fibrinolytic system (primary, secondary and tertiary hemostasis, respectively) normally ensure an adequate hemostatic balance. Disruption of this interplay can lead to thrombotic or hemorrhagic tendency. Primary hemostasis Primary hemostasis entails the activation, adhesion and aggregation of platelets onto a damaged site in a vessel wall. The exposure of platelets to the damaged vessel wall initiates primary hemostasis. The exposed subendothelial elements further promote the recruitment of platelets in order to repair the defect. The presence of multimeric protein von Willebrand factor (VWF) at the site of injury is the key step in the mechanism of endothelial reparation. Circulating VWF will bind to the exposed subendothelial collagen and adhere to the platelet membrane. For further progression of plug formation, activation of feedback between nearby platelets is also necessary and mediated by agonists such as adenosine diphosphate and thromboxane A2.(1,2) Regulation of the multimeric VWF is essential for hemostasis; its main inhibitor is ADAMTS13 (a disintegrin an metalloproteinase with a thrombospondin type 1 motif, member 13). Coagulation Coagulation or secondary hemostasis is a complex interplay of pro- and anticoagulant proteins which leads to the generation of thrombin. The widely known classic pathway of coagulation includes the intrinsic and extrinsic coagulation pathway and uses the sequential activation of coagulation factors leading to the formation of thrombin. The cell based model reflects in vivo hemostasis more accurately and does not present coagulation as a cascade but it suggests coagulation presents in overlapping stages.(3–5) Coagulation starts when tissue factor (TF) is exposed to the bloodstream.(2) Factor VII gets in contact with TF through exposed extravascular tissues. These two factors form a complex, activate factor IX and X, and serve as a bridge between extrinsic and intrinsic pathway. The complex of factor Xa and factor V that is formed activates factor II (prothrombin to thrombin). Next to multiple positive feedback loops, the negative feedback loop of thrombin generation is regulated by protein C, S and tissue factor pathway inhibitor (TFPI).(6)