Hemostasis clot formation

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

Hemostasis is the process that stops bleeding in a blood vessel. Normal hemostasis involves a complex process of extrinsic and intrinsic factors. Figure 44-1 shows the coagulation pathway and factors involved. The copulation cascade is so named because as each factor is activated it acts as a catalyst that enhances the next reaction, with the net result being a large collection of fibrin that forms a plug in the vessel. Fibrin is the insoluble protein that is essential to clot formation. 

Hemostasis Cessation of bleeding through natural (clot formation or constriction of blood vessels), artificial (compression or ligation), or surgical means. 

Platelets play a role in each of the mechanisms of normal hemostasis vasoconstriction, formation of the platelet plug, and blood coagulation. However, they are also involved in pathological processes that lead to atherosclerosis and thrombosis (formation of a blood clot within the vascular system). Antiplatelet drugs interfere with platelet function and are used to prevent the development of atherosclerosis and formation of arterial thrombi. 

Hemostasis is the process of blood clot formation at the site of vessel injury. When a blood vessel wall breaks, the hemostatic response must be rapid, localized, and carefully regulated. Abnormal bleeding or a propensity to nonphysiologic thrombosis (i.e., thrombosis not required for hemostatic regulation) may occur when specific elements of these processes are missing or dysfunctional. The elements responsible for normal hemostasis have received extensive review. 

The balance between clot formation and breakdown is crucial in maintaining normal hemostasis. Obviously, clots should not be broken down as quickly as they are formed because then no coagulation will occur. Likewise, a lack of breakdown would enable clots to proliferate at an excessive rate, leading to thrombus formation. 

Platelet participation in normal hemostasis. The hemostatic plug is the specific response to external vessel lesion and depends on the extent of vessel wall damage, the specific interaction between endothelial cells and activated platelets, release of the contents of platelets intracellular granules in response to activation, the conjoint activity of activated factor Vll and platelet agonists, and the open conditions of blood flow. After activation, platelets also produce the external ization of membrane phosphatidylserine through the flip-flop mechanism that will support the function of the prothrombinase complex ending in thrombin generation and local clot formation. 

Upon vascular injury, the coagulation system is activated thrombocytes and fibrin molecules coalesce into a plug that seals the defect and halts bleeding (hemostasis). Unnecessary formation of an intravascular clot—a thrombosis—can be life-threatening. 

In humans, dextran administration is associated with a decrease in factor VIII activity, decreased fibrin clot formation and dilutional coagulopathy (Roberts Bratton 1998). Dextran 70 inhibits equine platelet aggregation in vitro (Heath et al 1998) but other effects on hemostasis have not been investigated. Dextran 70 has been used for its presumed antithrombotic properties in horses with a clinical diagnosis of verminous aneurysm (Table 17.9) (Greatorex 1977). Dextran 70, when combined with hypertonic saline, resulted in a... 

Activated protein C in conjunction with its cofactor, protein S, plays a key role in the anticoagulant system by inactivating membrane-bound factors Va and Villa, The inability to inactivate procoagulant factors Va or Villa could disturb hemostasis, heighten the coagulation pathway, increase the generation of thrombin, and promote clot formation. In 1993 Dahlback reported familial thrombophilia caused by resistance to activated protein C (APC). In 1994... 

The clinical presentation of these two types of priapism is different. HFP is often seen after an acute injury, and the onset can be delayed. This delayed onset may be due to initial vessel spasm, hemostasis with clot formation or a compressing hematoma. Reabsorption of this clot or hematoma is the mechanism for the late onset. The HFP is often less tumescent when compared with venous priapism. Priapism secondary to arterial causes maybe, as mentioned before, significantly less painful than venous priapism and is not considered as an emergency. The major etiology of HFP is trauma, especially in children or young adults in older men, HFP is a rare event mainly caused by malignancy [2]. High-flow priapism in acute lymphatic leukaemia has also been reported [3]. 

Hemostasis is the cessation of bleeding from a cut or severed vessel, whereas thrombosis occurs when the endothelium lining blood vessels is damaged or removed (eg, upon rupmre of an atherosclerotic plaque). These processes encompass blood clotting (coagulation) and involve blood vessels, platelet aggregation, and plasma proteins that cause formation or dissolution of platelet aggregates. 

We shall first describe the coagulation pathway leading to the formation of fibrin. Then we shall briefly describe some aspects of the involvement of platelets and blood vessel walls in the overall process. This separation of clotting factors and platelets is artificial, since both play intimate and often mutually interdependent roles in hemostasis and thrombosis, but it facifitates description of the overall processes involved. 

Blood coagulation. The third major step in hemostasis is coagulation, or the formation of a blood clot. This complex process involves a series of reactions that result in formation of a protein fiber meshwork that stabilizes the platelet plug. Three essential steps lead to clotting (see Figure 16.1) ... 

Following injury to blood vessels, hemostasis ensures that blood loss is minimized. Initially, thrombocyte activation leads to contraction of the injured vessel and the formation of a loose clot consisting of thrombocytes (hemostasis). Slightly later, the action of the enzyme thrombin leads to the formation and deposition in the thrombus of polymeric fibrin (coagulation, blood clotting). The coagulation process is discussed here in detail. 

Two separate pathways, intrinsic and extrinsic, lead to the formation of a fibrin clot. Both pathways must function for hemostasis. 

Hemostasis begins with the formation of the platelet plug, followed by activation of the clotting cascade, and propagation of the clot. One of the major multicomponent complexes in the coagulation cascade consists of activated factor IX (factor IXa) as the protease, activated factor VIII (factor Villa), calcium, and phospholipids as the cofactors, and factor X as the substrate. Factor IXa can be generated by either factor Xa activation of the intrinsic pathway or by the tissue factor/factor Vila complex. 

Normal hemostasis is a balance between excessive and inadequate blood clotting. Overactive blood clotting is harmful because of the tendency for thrombus formation and occlusion of arteries and veins. Vessels may become directly blocked by the thrombus, or a portion of the thrombus may break off and create an embolism that lodges elsewhere in the vascular system. The tendency for excessive thrombus formation in the venous system is usually treated with anticoagulant drugs such as heparin and warfarin. Platelet inhibitors such as aspirin help prevent arterial thrombogenesis. Thrombolytic drugs (streptokinase, t-PA) that facilitate the dissolution of harmful clots may successfully reopen... 

---