Fibrinogen clots

Rgure 7 Course of fibrinogen clotting (measured Unhid i metrically) an addition of 5 NIH-U tfirombin (T) and benzoyl-thrombin [Pg.62]

In the 1940 s and early 1950 s most cells were grown in plasma or fibrinogen clots, in the presence of tissue extracts and their ultra-... 

Bleeding disorder similar to Glanzmann thrombasthenia in man platelets failed to bind fibrinogen, to aggregate and to retract a fibrinogen clot a-granules do not contain fibrinogen (Tronik-Le Roux et al. 2000). 

The covalent modification of human a-thrombin with pyridoxal 5 -phosphate involves phosphopyridoxylation at two sites.Attachment of the cofactor to the first site was accompanied by a loss in the fibrinogen clotting activity of the thrombin, whereas attachment of the cofactor to the second site resulted in a decrease in the sensitivity to heparin in the anti-(thrombin III)-thrombin reaction. 

A third form of fibrinogen dyscrasia is of unknown origin. There is a low level of normal fibrinogen clots form but they are small and soft. The cause of the defect is not known. 

Thrombin, the two-chain derivative of the prothrombin molecule, has a molecular weight of approximately 37,000 daltons. Its proteolytic properties induce the conversion of fibrinogen to fibrin to produce the initial visible manifestation of coagulation, the soluble fibrin clot. In addition, thrombin influences the activity of Factors V, VIII, and XIII and plasmin. Thrombin affects platelet function by inducing viscous metamorphosis and the release reaction with subsequent aggregation. 

Arvin [9046-56-4] is a purified fraction from the cmde venom of Agkistrodon rhodostoma (48). The action of this venom fraction is selectively specific for fibrinogen and can rapidly deplete fibrinogen in vivo safely from the ckculating blood. Blood without fibrinogen cannot undergo clot formation. 

Tissue Plasminogen Aetivator (tPA). While streptokinase and urokinase can effectively induce clot dissolution in the majority of patients if given early, they lack clot specificity. Treatment with these enzymes results in a systemic lytic state attributable to their degradative action on circulating fibrinogen. Tissue plasminogen activator (tPA) was developed to achieve rapid and specific thrombolysis. 

FIGURE 15.5 The cascade of activation steps leading to blood clotting. The intrinsic and extrinsic pathways converge at Factor X, and the final common pathway involves the activation of thrombin and its conversion of fibrinogen into fibrin, which aggregates into ordered filamentous arrays that become cross-linked to form the clot. 

Heparin inhibits the formation of fibrin clots, inhibits the conversion of fibrinogen to fibrin, and inactivates several of the factors necessary for the clotting of blood. Heparin cannot be taken orally because it is inactivated by gastric acid in the stomach therefore, it must be given by injection. Heparin has no effect on clots that have already formed and aids only in preventing the formation of new blood clots (thrombi). The LMWHs act to inhibit clotting reactions by binding to antithrombin HI, which inhibits the synthesis of factor Xa and the formation of thrombin. 

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