Hemostasis is a complex interaction between vessels, platelets and coagulation proteins that, when working properly, stops bleeding while maintaining blood flow in the vessel. Hemostasis involves four distinct but at the same time interrelated functions: vessel wall function, platelet function, coagulation and fibrinolysis. Specific tests are available to evaluate platelet function, coagulation proteins, natural occurring inhibitors and fibrinolysis. Research assays are available to evaluate vessel wall function and damage. Platelets play an immediate and central role in hemostasis. Qualitative and/or quantitative defects may exist which lead to excessive bleeding. When vascular injury occurs, the subendothelium is exposed and in the presence of von Willebrand factor, platelets adhere to collagen. Stimulated platelets release ADP (which potentiates platelet aggregation), expose anionic phospholipid, and release factor V and fibrinogen, which promotes coagulation. The fragile primary platelet clot is quickly stabilized by fibrin formation via the coagulation cascade. For many years it was thought that coagulation proceeded via two distinct pathways, intrinsic and extrinsic, with the difference between the two being the method of activation. Today, we understand that only a single pathway exists for coagulation activation that occurs in two phases. The first phase of coagulation activation, termed the initiation phase, is dependent on exposure or transport of tissue factor to the site of the wound. Thrombin generation is slow during the initiation phase. As thrombin levels increase, thrombin activates additional platelets and factors V, VIII and XI which dramatically increases the rate of thrombin generation leading to fibrin and clot formation, this is termed the propagation phase. In vivo, almost all coagulation reactions are initiated by exposure of tissue factor and platelet activation. Tissue factor autocatalyzes factor VII to VIIa. Factor VIIa in turn activates factor IX, IXa activates X, Xa converts prothrombin to thrombin, finally resulting in conversion of fibrinogen to fibrin. In the activated partial thromboplastin time (APTT) test, the contact system is activated which in turn initiates the “intrinsic” coagulation pathway through factor XIIa. Contact phase factors include prekallikrein, high molecular weight kininogen, and factor XII, which when activated convert factor XI to XIa. Factor XIa converts IX to IXa, which then activates factor X which in turn converts prothrombin into thrombin. In vivo there are a variety of control mechanisms to limit thrombus formation through the naturally occurring inhibitors protein C, protein S and antithrombin. Thrombomodulin present on the endothelial surface binds thrombin, “modulating” its specificity and turning thrombin into an activator of protein C. Activated protein C, with its cofactor protein S, proteolytically degrades factors Va and VIIIa. Thrombin in plasma is inhibited by antithrombin. This reaction is accelerated by heparinoids on the endothelial surface and heparin given therapeutically. Activated Protein C is regulated by activated protein C inhibitor (APCI). Protein S exists in two forms in plasma: free and bound to C4b-binding protein. Only the free form of protein S is active. The fibrinolytic system plays an important role in regulating the formation and removal of thrombi. Fibrinolysis is initiated by the release of tissue plasminogen activator (tPA) from vascular endothelial cells. tPA, in the presence of fibrin, converts plasminogen to plasmin, which in turn lyses fibrin in the thrombus. The concentration of tPA in circulating blood is regulated by the secretion of tPA by the vascular endothelium, clearance of tPA by the liver and the inhibition of tPA by plasminogen activator inhibitor type 1 (PAI-1). The concentration of plasmin in the blood is regulated by antiplasmin (aka plasmin inhibitor). Increased levels of fibrinolytic activity in blood are associated with bleeding, while decreased