Thrombosis coagulation cascade

Describe the processes of hemostasis and thrombosis, including the role of the vascular endothelium, platelets, coagulation cascade, and thrombolytic proteins. 

Pharmacologic techniques counteract the propensity for thrombosis formation by dampening the coagulation cascade. Appropriately selected therapy can dramatically reduce the incidence of VTE after hip or knee replacement, general surgery, myocardial infarction, and ischemic stroke. 

Pathophysiologically, thrombosis is the same sequence of events but now occurring in abnormal anatomical sites with intravascular obstruction that results in distal tissue ischaemia. These are often systemic disorders affecting the whole circulation and are described as hypercoagulable syndromes. Defects may lie at the level of the endothelium, inappropriate activation of the coagulation cascade or impaired activity of the fibrinolytic system. Segments of thrombus can become detached and travel peripherally in arterial tree, giving rise to acute insufficiency. Conversely, on the venous side, these are... 

Thrombus versus embolus A clot that adheres to a vessel wall is called a thrombus, whereas an intravascular clot that floats within the blood is termed an embolus. Thus, a detached thrombus becomes an embolus. Both thrombi and emboli are dangerous, because they may occlude blood vessels and deprive tissues of oxygen and nutrients. Arterial thrombosis most often involves medium-sized vessels rendered thrombogenic by surface lesions of endothelial cells caused by atherosclerosis. In contrast, venous thrombosis is triggered by blood stasis or inappropriate activation of the coagulation cascade, often as a result of a defect in the normal defense hemostatic mechanisms. 

Five known mechanisms regulate the coagulation cascade. Abnormalities can lead to an increased tendency towards thrombosis ... 

Die begins with the activation and production of the proinflam-matory cytokines such as TNF, IL-1, and IL-6, which appear to be the principal mediators, along with endotoxin, of endothelial injury, activation of the coagulation cascade, and inhibition of fibrinolysis. The combination of excessive fibrin formation, inhibited fibrin removal from a depressed fibrinolytic system, and endothelial injury results in microvascular thrombosis and DIC. ... 

Thrombin (factor Ha) is the last enzyme protease involved in the coagulation cascade, and it converts fibrinogen to insoluble fibrin that forms the fibrin gel either in physiological conditions or in a pathological thrombus (28). Thrombin has also hormonelike properties, and it is involved in thrombosis and platelet activation. Therefore, thrombin plays a central role in a number of cardiovascular diseases (29), and it is thought to regulate many processes in inflammation and tissue repair at the vessel wall. 

Fondaparinux is a selective inhibitor factor Xa possessing a selective inhibition of antithrombin III (ATIII), which potentiates the innate neutralization of factor Xa by ATIII. Nentralization of factor Xa interrupts the blood coagulation cascade and inhibits thrombin formation and thrombus development. It is indicated for prophylaxis of deep vein thrombosis (DVT) that may lead to pulmonary embolism in patients undergoing hip fracture surgery including extended prophylaxis, hip replacement surgery, or knee replacement surgery. When administered in conjunction with warfarin, fondaparinux is indicated for treatment of acute DVT and acute pulmonary embolism. 

Regulatory mechanisms within the blood coagulation cascade and antifibrinolytic mechanisms prevent random coagulation within blood vessels that might obstruct blood flow. Impairments in these mechanisms lead to thrombosis. 

Because plaque mpture and subsequent thrombosis are the initial events in most myocardial infarctions, there has been an interest in inhibiting both platelet aggregation and the coagulation cascade in patients at risk for an event. Traditionally, such... 

The rat carotid artery injured by a balloon catheter has been widely used as a model of angioplasty. The rat model is a proliferation model without foam cells (93). This form of injury causes immediate coagulation and thrombosis cascade in which platelets adhere, spread, and degranulate on the denuded surface of the artery, and approximately 24 hours later SMC begin to proliferate. Liposomal BPs, clodronate, and alendronate were injected to male sabra rats, 15 and 3mg/kg, respectively (52,69,76). Marked neointimal formation and decreased luminal area were observed in control animals. Neointima/media (N/M) ratio was 1.3 0.2, and luminal stenosis was 44 3%. LC and LA suppressed intimal growth when administered intravenously on day -1 and day 6. N/M ratios were reduced by 60% and 69% for LC and LA, respectively. 

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