bleeding and blood clottingdisease

The evolution of high-pressure blood circulation in vertebrates has brought with it the risk of bleeding after injury to tissues. Mechanisms to prevent bleeding (i.e., hemostatic mechanisms) are essential to maintain the closed blood-circulatory system. Normal hemostasis is the responsibility of a complex system of three individual components: blood cells (platelets), cells that line the blood vessels (endothelial cells), and blood proteins (blood-clotting proteins). The blood platelet is a nonnucleated cell that circulates in the blood in an inactive, resting form. Endothelial cells line the wall of the blood vessel and inhibit blood from clotting on the vessel wall under normal conditions. Blood-clotting proteins circulate in the blood plasma in an inactive form, poised to participate in blood coagulation upon tissue injury. Blood-clotting proteins generate thrombin, an enzyme that converts fibrinogen to fibrin, and a reaction that leads to the formation of a fibrin clot.

The hemostatic mechanism involves three physiologically important reactions: (1) the formation of a blood clot, (2) the formation of a platelet plug, and (3) changes associated with the wall of the blood vessel after injury of its cells. In humans, defects in any of these processes may result in persistent bleeding from slight injuries, or, alternatively, in an overreaction that causes the inappropriate formation of blood clots (thrombosis) in blood vessels. When a blood vessel is injured, blood escapes for as long as the vessel remains open and the pressure within the vessel exceeds that outside. Blood flow can be stopped or diminished by closing the leak or by equalizing the pressure. The leak may be closed by contraction of the blood vessel wall or by the formation of a solid plug. Pressure may be equalized by an increase in external pressure as blood becomes trapped in the tissues (hematoma) or by a decrease in the intravascular pressure (the pressure within the blood vessel) caused by constriction of a supply vessel. The timing and relative importance of these events can vary with the scale of the injury. Bleeding from the smallest vessels can be stopped by platelet plugs; when bleeding is from larger vessels, blood clot formation is required; in still larger vessels the severe drop in pressure associated with shock is the last line of defense.