Clot formation

The calcium ion, necessary for blood-clot formation, stimulates release of bloodclotting factors from platelets (see Blood, coagulants and anticoagulants) (25). Neuromuscular excitabihty also depends on the relative concentrations of Na", Ca ", Mg ", and (26). Upon a decrease in... 

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. 

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). 

Hirudin is a polypeptide derived from the saliva of the leech Hirudo medicinalis that binds to the blood serine proteinase, thrombins, and thus blocks clot formation. 

The international normalized ratio (INR) is a method to standardize repotting of the prothrombin time, using the formula, INR = (PTpatie t/PTcontroi)ISI, where PT indicates the prothrombin times (for the patient and the laboratory control), and ISI indicates the international sensitivity index, a value that varies, depending upon the thromboplastin reagent and laboratory instrument used to initiate and detect clot formation, respectively. 

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. 

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. 

Angiotensin II is a neurohormone produced primarily in the kidney. It is a potent vasoconstrictor and stimulates the production of aldosterone. Together, angiotensin II and aldosterone increase blood pressure and sodium and water retention (increasing ventricular wall tension), cause endothelial dysfunction, promote blood clot formation, and cause myocardial fibrosis. 

Duplex ultrasonography is the most commonly used test to diagnosis DVT. It is a non-invasive test that can measure the rate and direction of blood flow and visualize clot formation in proximal veins of the legs. It cannot reliably detect small blood clots in distal veins. Coupled with a careful clinical assessment, it can rule in or out (include or exclude) the diagnosis in the majority of cases. 

FIGURE 8-3. The physiologic clotting cascade. Clot formation beginning with vessel or tissue injury. Tissue injury starts the complex process involving clotting factors and resulting in cross-linked fibrin. This is a schematic of the factors and steps involved in the process. 

Deep vein thrombosis A disorder of thrombus (blood clot) formation causing obstruction of a deep vein in the leg, pelvis, or abdomen. 

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

Phenyl indandiones With an acidic hydrogen often interfere with clot formation. When electron withdrawing groups are present in the p-position, acidity is increased and activity goes up. The opposite effect is seen with electron-donating substituents. Synthesized in the usual way, the anticoagulant bromindione (15) results from sodium acetate-catalyzed condensation of phthalic anhydride and p-a-bromophenyl-acetic acid. ... 

Positive feedback nature of clot formation. Thrombin promotes clot formation at several points in the coagulation cascade through positive feedback. Activities of thrombin include ... 

Surfactin Bacterial lipopeptide biosurfactant inhibits clot formation (387)... 

Development of the LAL assay was based upon the observation that the presence of Gramnegative bacteria in the vascular system of the American horseshoe crab, Limulus polyphemus, resulted in the clotting of its blood. Tests on fractionated blood showed that the factor responsible for coagulation resided within the crab s circulating blood cells, i.e. the amoebocytes. Further research revealed that the bacterial agent responsible of initiation of clot formation was endotoxin. 

Figure 7.8 Activation of clot formation by endotoxin. The presence of endotoxin causes stepwise, sequential activation of various clotting factors present naturally within the amoebocytes of the American horseshoe crab. The net result is the generation of the polypeptide fragment coagulin, which polymerizes, thus forming a gel or clot...

Although blood clot formation is essential to maintaining haemostasis, inappropriate clotting can give rise to serious, sometimes fatal medical conditions. The formation of a blood clot (a thrombus) often occurs inappropriately within diseased blood vessels. This partially or completely obstructs the flow of blood (and hence oxygen) to the tissues normally served by that blood vessel. 

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