Hemostasis coagulation factors

Kleinschnitz C, Stoll G, Bendszus M et al (2006) Targeting coagulation Factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med 203 513-518... 

Hemostasis and thrombosis are complex processes involving coagulation factors, platelets, and blood vessels. 

The main goal of recessively inherited coagulation disorder (RICD) treatment is to prevent and control spontaneous and surgery-related bleeding episodes. Specifically, therapeutic options improve hemostasis via replacement of deficient blood coagulation factors while minimizing the development of immune tolerance.20... 

To maintain hemostasis, blood must be retained in the vasculature as fluid. At the same time, blood components must be able to respond rapidly with a clot when a vascular injury occurs. To repair a vascular injury, platelets in blood first adhere as aggregates to the endothelial cells at the affected site and form an initial blood clot. Platelets then stimulate and activate coagulation factors found in plasma to form a more stable fibrin clot. As the injury is resolved and healed, the clot is degraded. Thrombosis is a pathological event wherein a blood clot occludes a blood vessel, resulting in ischemic necrosis of the tissue fed by the blood vessel. Ischemic necrosis involves local anemia and oxygen deprivation. Thrombosis of a coronary artery may lead to myocardial infarction or unstable angina [20]. 

Connolly AJ, Ishihara H, Kahn ML et al. (1996) Role of the thrombin receptor in development and evidence for a second receptor. Nature 381 516-519 Cui J, O Shea KS, Purkayastha A et al. (1996) Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Nature 384 66-68 Denis C, Methia N, Frenette PS et al. (1998) A mouse model of severe von Willebrand disease defects in hemostasis and thrombosis. Proc Nad Acad Sci USA 95 9524-9529 Dewerchin M, Liang Z, Moons L et al. (2000) Blood coagulation factor X deficiency causes partial embryonic lethality and fatal neonatal bleeding in mice. Thromb Haemost 83 185-190... 

FIGURE 108-2. Cell-based model of hemostasis. TF, tissue factor TFPI, tissue factor pathway inhibitor vWF, von Willebrand factor. (Reproduced from Roberts HR etal. Molecular biology and biochemistry of the coagulation factors and pathways of hemostasis. In Beutler et al. Williams Hematology, 6th ed. New York, McGraw-Hill, 2001, pp 1409-1434.)... 

Vasopressin also is a potent vasopressor whose name was chosen in recognition of its vasoconstrictor action. Vasopressin is a neurotransmitter among its actions in the CNS are apparent roles in the secretion of ACTH and in the regulation of the cardiovascular system, temperature, and other visceral functions. Vasopressin also may play a role in hemostasis by promoting the release of coagulation factors by the vascular endothelium and increasing platelet aggregation. 

The metabolic countermeasures are characterized by the regulatory role of ascorbate for metabolic systems determining the clinical risk profile for CVD. The common aim of these metabolic regulations is to decrease the vascular permeability in ascorbate deficiency. Low ascorbate concentrations therefore induce vasoconstriction and hemostasis and affect vascular wall metabolism in favor of atherosclerogenesis. Towards this end ascorbate interacts with lipoproteins, coagulation factors, prostaglandins, nitric oxide, and second messenger systems such as cyclic monophosphates (for review see 1, 3-5). It... 

Although the factors in the blood probably play a central role in blood coagulation, other factors—the platelet count and vascular reaction—are involved in controlling hemostasis. Consequently, hemorrhagic disease may result from interference with the activity of one or more factors involved in blood coagulation, from absent platelets, or from vascular disorders. At this point, we will only discuss those hemorrhagic diseases that result from transient reduction of coagulating factors. 

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). 

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