Fibrin clot

They release adenosine diphosphate [58-64-0 (ADP) and thromboxane [57576-52-0] which results in vascular contraction and, indirectiy, in the formation of fibrin clot. Platelet transfusions are indicated for patients with thrombocytopenia, ie, a shortage of healthy platelets or thrombocytopathy, ie, platelet malignancy associated with spontaneous hemorrhages. 

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. 

Thrombolytic Enzymes. Although atherosclerosis and the accompanying vascular wall defects are ultimately responsible for such diseases as acute pulmonary embolism, arterial occlusion, and myocardial infarction, the lack of blood flow caused by a fibrin clot directly results in tissue injury and in the clinical symptoms of these devastating diseases (54). Thrombolytic enzyme therapy removes the fibrin clot by dissolution, and has shown promise in the treatment of a number of thrombo-occlusive diseases (60). 

Streptokinase. The fibrinolytic activity of streptokinase, isolated from strains of hemolytic Streptococci, was first demonstrated in 1933 (63). Streptokinase is a secreted protein product inasmuch as filtrates free of demonstrable bacteria were found to dissolve fibrin clots with rapidity. 

Streptokinase dissolves such fibrin clots, thereby permitting effective antibiotic therapy (201). 

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. 

Although the exact action of the thrombolytic dragp is slightly different, these drugs break down fibrin clots by converting plasminogen to plasmin (fibrinolysin). Plasmin is an enzyme that breaks down the fibrin of a blood clot. This reopens blood vessels after their occlusion and prevents tissue necrosis. 

When using urokinase to clear an occluded IV catheter, the nurse follows the manufacturer s instructions in the packaged insert. The nurse avoids using excessive pressure when the drug is injected into the catheter. Excessive force could rupture the catheter or expel the clot into the circulation. It is important to remember that if the catheter is occluded by substances other than blood fibrin clots, such as drug precipitates, urokinase is not effective. 

Two pathways lead to fibrin clot formation the intrinsic and the extrinsic pathways. These pathways are not independent, as previously thought. However, this artificial distinction is retained in the following text to fa-cihtate their description. 

Initiation of the fibrin clot in response to tissue injury is carried out by the extrinsic pathway. How the intrinsic pathway is activated in vivo is unclear, but it involves a negatively charged surface. The intrinsic and extrinsic pathways converge in a final common path-vray involving the activation of prothrombin to thrombin and the thrombin-catalyzed cleavage of fibrinogen to form the fibrin clot. The intrinsic, extrinsic, and final common pathways are complex and involve many different proteins (Figure 51-1 and Table 51-1). In... 

Figure 51-5. Formation of a fibrin clot. A Thrombin-induced cleavage of Arg-Gly bonds of the Aaand B(3 chains of fibrinogen to produce fi-brinopeptides (left-hand side) and the a and p chains of fibrin monomer (right-hand side). B Cross-linking of fibrin molecules by activated factor XIII (factor Xllla).

A number of laboratory tests are available to measure the phases of hemostasis described above. The tests include platelet count, bleeding time, activated partial thromboplastin time (aPTT or PTT), prothrombin time (PT), thrombin time (TT), concentration of fibrinogen, fibrin clot stabifity, and measurement of fibrin degradation products. The platelet count quantitates the number of platelets, and the bleeding time is an overall test of platelet function. aPTT is a measure of the intrinsic pathway and PT of the extrinsic pathway. PT is used to measure the effectiveness of oral anticoagulants such as warfarin, and aPTT is used to monitor heparin therapy. The reader is referred to a textbook of hematology for a discussion of these tests. 

Fibrinolysins are produced by both staphylococci (staphylokinase) and streptococci (streptokinase). These toxins dissolve fibrin clots, formed by the host around wounds and lesions to seal them, by indirect activation of plasminogen, thereby increasing the likelihood of organism spread. Streptokinase m be employed elinieally in conjunction with streptodomase (Chapter 25) in the treatment of thrombosis. 

Activated partial thromboplastin time aPTT is performed by adding calcium phospholipids and kaolin to citrated blood and measures the time required for a fibrin clot to form. In this manner, aPTT measures the activity of intrinsic and common pathways. Prolongation of aPTT may be due to a deficiency or inhibitor for factors II, V, VIII, IX, X, XI, and XII. It also may be due to heparin, direct thrombin inhibitors, vitamin K deficiency, liver disease, or lupus anticoagulant. 

Thrombin time is an assessment of the time required for the appearance of the fibrin clot after thrombin is added... 

Von dem Borne P. A. K., Meijers J. C. M., Bouma B. N. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood 1995 86, 3035 -42. 

Mosesson MW. Fibrinogen and fibrin polymerization appraisal of the binding events that accompany fibrin generation and fibrin clot assembly. Blood Coagul Fibrinol 1997 8 257-267. 

Yang SH et al (2008) Three-dimensional culture of human nucleus pulposus cells in fibrin clot comparisons on cellular proliferation and matrix synthesis with cells in alginate. Artif Organs 32(l) 70-73... 

Hirudin exhibits its anticoagulant effect by tightly binding thrombin, thus inactivating it. In addition to its critical role in the production of a fibrin clot, thrombin displays several other (non-enzymatic) biological activities important in sustaining haemostasis. These include ... 

The ability of some component of human urine to dissolve fibrin clots was first noted in 1885. It was not until the 1950s, however, that the active substance was isolated and named urokinase. 

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