Clot formation, mechanism

Mechanism of Action A blood modifier that interferes with blood coagulation by blocking conversion of prothrombin to thrombin and fibrinogen to fibrin Therapeutic Effect Prevents further extension of existing thrombi or new clot formation. Has no effect on existing clots. 

Mechanism of Action A coumarin derivative that interferes with hepatic synthesis of vitamin K-dependent clotting factors, resulting in depletion of coagulation factors II, VII, IX, and X. Therapeutic Effect Prevents further extension of formed existing clot prevents new clot formation or secondary thromboembolic complications. Pharmacokinetics ... 

FIGURE 25-1 Mechanism of blood coagulation. Factors involved in clot formation are shown above the dashed line factors involved in clot breakdown are shown below the dashed line. See text... 

SidelmannJJ, Gram J, Jespersen J, Kluft C. Fibrin clot formation and lysis basic mechanisms. Semin Thromb Hemost. 2000 26 605-618. 

The saliva of the medicinal leech contains a battery of substances that interfere with the hemostatic mechanisms of the host. One of these compounds is hirudin, a potent anticoagulant, which maintains the fluidity of the ingested blood and is the most potent inhibitor of thrombin. Upon binding to thrombin, the cleavage of fibrinogen and subsequent clot formation are prevented. The potency and specificity of hirudin make it a useful antithrombin-III-independent alternative to heparin for the control of thrombosis. 

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. 

The most important mechanism that underlies the MR appearance of ICH is the transformation of initially oxygenated hemoglobin into a series of breakdown products (deoxyhemoglobin, methemoglobin, and hemosiderin), that differ in terms of presence and number of unpaired electrons of the heme iron. Hereafter, we will discuss the influence of hemoglobin and its metabolites on T1 and T2 relaxation times. We will also briefly review the effects on MR signals of other factors such as protein concentration, clot formation and retraction, and red blood cell dehydration. 

There is a fine line between hemorrhage and thrombosis. Clots must form rapidly yet remain confined to the area of injury. What are the mechanisms that normally limit clot formation to the site of injury The lability of clotting factors contributes significantly to the cont ol of clotting. Activated factors are short-lived because they are diluted by blood flow, removed by the liver, and degraded by proteases. For example, the stimulatory protein factors V , and VIIC are digested by protein C, a protease that is switched on by the action of thrombin. Thus, thrombin has a dual function it catalyzes the formation of fibrin and it initiates the deaclivation of the clotting cascade. 

The coagulation system regulates fibrin clot formation, whereas the fibrinolytic system dissolves the polymerized clot and restores blood flow. As a regnlatory mechanism to maintain blood flow, the fibrinolytic system removes fibrin deposits and prevents formation of unnecessary fibrin clots. It also contributes to the localized repair of damaged endothelium. 

The use of an appropriate mammalian species for biocompatibility studies often has been a topic of heavy debate. The rationale for use of the dog in our system was based primarily on availability of subjects and cost. In addition, the adherence of dog platelets to cuprophane membranes was reported to be three orders of magnitude greater than the adherence of human platelets (41). The dog is also thought to have a highly potent fibrinolytic system (42). Thus, the dog should be a very sensitive animal for studying clot formation and dissolution. A clearer visualization of the mechanisms involved should therefore be possible. We believe that fundamental mechanisms underlie artificial surface-induced thrombosis and embolization in dogs, humans, and other mammalian species. 

This chapter will review the basic mechanisms of clot formation (thrombosis) and dissolution (thrombolysis or fibrinolysis), the mechanisms of the major drug classes used in the treatment, and the results from major clinical trials. This chapter will also present evidence-based recommendations and protocols for applying thrombolytic therapy to individual patients. 

The efficacy of chitosan as a haemostatic agent is another example. In vitro studies with blood have indicated that its haemostatic mechanism is independent of the classical coagulation cascade and it is due to an interaction between the cell membrane of erythrocytes and chitosan, with clot formation in the absence of coagulation factors or platelets, according to early reports by Klokkevold et al. 

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]. 

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