Anticoagulants
COAGULATION AND THROMBI
Haemostasis, the physiological response to vascular injury, results in the formation of a haemostatic plug that prevents blood loss. Under normal conditions, factors that promote blood coagulation are balanced by those that inhibit it. Pathologic thrombosis occurs when procoagulant stimuli overwhelm natural anticoagulant and fibrinolytic systems.
Venous thrombi, which form under low shear conditions, are predominantly composed of fibrin and red cells. Thrombi may develop anywhere within the venous system but most commonly arise in the deep veins of the leg through an interplay among 3 factors that include vessel wall damage, venous stasis, and hypercoagulability. Direct damage to the veins helps explain the propensity to deep vein thrombosis (DVT) after major orthopedic surgery. Thrombi often originate in the calf, either in the muscular sinuses or valve cusps of deep veins. Immobility delays emptying of muscular veins and retards clearance of activated clotting factors. With stasis, endothelial cells lining the avascular valve cusps are activated by hypoxemia, a process exacerbated by inflammatory cytokines generated postoperatively or in medical illness. Leukocytes tethered to activated endothelial cells express tissue factor, whereas platelets become activated and aggregate. Congenital or acquired disorders associated with hypercoagulability promote coagulation at these sites, thereby increasing the risk of thrombosis. Signs and symptoms develop when there is obstruction to venous outflow and inflammation of the vessel wall and perivascular tissue. Symptoms of pulmonary embolism arise when segments of thrombus detach and embolize to the pulmonary circulation.
Arterial thrombi form under high shear conditions and are composed primarily of platelet aggregates held together by fibrin strands. Obstruction of anterograde arterial flow leads to ischemia, which manifests as unstable angina or myocardial infarction in the case of coronary
Haemostasis, the physiological response to vascular injury, results in the formation of a haemostatic plug that prevents blood loss. Under normal conditions, factors that promote blood coagulation are balanced by those that inhibit it. Pathologic thrombosis occurs when procoagulant stimuli overwhelm natural anticoagulant and fibrinolytic systems.
Venous thrombi, which form under low shear conditions, are predominantly composed of fibrin and red cells. Thrombi may develop anywhere within the venous system but most commonly arise in the deep veins of the leg through an interplay among 3 factors that include vessel wall damage, venous stasis, and hypercoagulability. Direct damage to the veins helps explain the propensity to deep vein thrombosis (DVT) after major orthopedic surgery. Thrombi often originate in the calf, either in the muscular sinuses or valve cusps of deep veins. Immobility delays emptying of muscular veins and retards clearance of activated clotting factors. With stasis, endothelial cells lining the avascular valve cusps are activated by hypoxemia, a process exacerbated by inflammatory cytokines generated postoperatively or in medical illness. Leukocytes tethered to activated endothelial cells express tissue factor, whereas platelets become activated and aggregate. Congenital or acquired disorders associated with hypercoagulability promote coagulation at these sites, thereby increasing the risk of thrombosis. Signs and symptoms develop when there is obstruction to venous outflow and inflammation of the vessel wall and perivascular tissue. Symptoms of pulmonary embolism arise when segments of thrombus detach and embolize to the pulmonary circulation.
Arterial thrombi form under high shear conditions and are composed primarily of platelet aggregates held together by fibrin strands. Obstruction of anterograde arterial flow leads to ischemia, which manifests as unstable angina or myocardial infarction in the case of coronary
References: SITES  http://www.news-medical.net/?id=35364  http://www.chestjournal.org/cgi/content/full/119/1_suppl/95S  http://www.jbc.org/cgi/content/abstract/270/48/28629?ijkey=80ea56fd6d5cd82a7b01479c8cdd59e692c6cccb&keytype2=tf_ipsecsha  http://jpet.aspetjournals.org/cgi/content/full/292/1/351#SEC3  http://atvb.ahajournals.org/cgi/content/full/23/9/1491  http://www.jbc.org/cgi/content/abstract/281/49/37477  http://www.sciencemag.org/cgi/content/abstract/248/4955/593  http://bloodjournal.hematologylibrary.org/cgi/content/full/105/2/453