One of the remarkable properties of blood is its ability to clot, or coagulate, when it is withdrawn from the body. Inside the body, a clot is formed in response to tissue injury, such as muscle tear, a cut, or a sharp blow. In the blood vessels, the blood remains in a fluid condition: shortly after being withdrawn it becomes viscid and gelatinous and sets into a firm, jelly-like mass. This mass then separates into two positions, a firm red clot floating free in a transparent, straw-coloured fluid called serum.
A clot consists almost entirely of red corpuscles entangled in a network of fine fibrils or threads, composed of a substance called fibrin. It also contains platelets and plasma.
Certain substances promote coagulation (procoagulants) and others inhibit coagulation (anticoagulants). Clotting depends on the balance between procoagulants and anticoagulants in the blood. While the anticoagulants normally predominate the procoagulants get activated and cause clotting when a blood vessel is ruptured. Injury to a blood vessel causes a complex cascade of reactions leading to the formation of a clot. This is term as hemostasis. A temporary hemostatic platelet plug occurs after the initial event of constriction of the vessel and it is mediated by serotonin and other vasoconstrictors liberated from the platelets that adhere to the walls of damaged vessels.
This occurs when the platelets swell, become sticky and get aggregated, bind to the collagen and plug the hole. The loose aggregation of platelets in the temporary plug is bound together and converted into a definite clot by fibrin. This is the fundamental reaction in clotting which involves conversion of soluble plasma protein fibrinogen to insoluble fibrin.
The blood clotting factors are the inactive forms of proteolytic enzymes called serine dependent proteases. When activated they collectively form prothrombin activator via two pathways. This in the presence of calcium ions, converts prothrombin to thrombin which in turn causes the polymerization of fibrinogen to fibrin fibres within 10-15 seconds. They enmesh the platelets, blood cells and plasma forming clot. Thus, the rate limiting factor in blood coagulation is the formation of prothrombin activator. The clot begins to contract and express serum within 20-40 minutes. This process is called clot retraction. As the clot retracts the edges of a broken vessel are pulled together thus contributing to ultimate hemostasis. Addition of sodium citrate removes calcium ions from the blood and thus prevents clot. Lack of vitamin K makes impossible the maintenance of the proper amount of prothrombin in the blood. Certain diseases may lower the concentration of the various clotting proteins or of the platelets of the blood. But blood does not clot in blood vessels due to presence of anticoagulant ‘heparin’ secreted by the liver.
A deficiency in any of the factors necessary for blood coagulation leads to excessive bleeding. A decrease in platelets is known as thrombocytopenia; a decrease in clotting factor VIII results in hemophilia A (classic hemophilia); a decrease in clotting factor IX results in hemophilia B, commonly known as Christmas disease. Several of the hemorrhagic diseases, such as hemophilia, are hereditary. A genetic engineering technique for making VIII, a blood-clotting factor of vital importance for victims of the most common form of hemophilia, has been developed recently. Although clot formation is a normal process, it sometimes occurs inappropriately and constitutes a threat to life. In patients hospitalized for a long time, for example, clots form in the large vein of the legs. If these clots or thrombi travel to the lungs they can cause death.
Anticoagulants include the natural compound heparin, prepared from the lungs and livers of animals, and the synthetic chemicals dicumarol warfarin. Introduction of thrombocytes with the fatty deposits found in atherosclerotic heart disease is thought to contribute to heart attacks. Compounds such as aspirin and sulfinpyrazone, which inhibit platelet activity, may decrease heart attacks in person with atherosclerotic disease.
