Outline the process of coagulation. Explain how blood coagulation is affected by the following: (a) vitamin K deficiency (b) heparin (c) thrombocytes

Outline:

·        Initiation of coagulation

·        Extrinsic mechanism for initiating clotting

·        Intrinsic mechanism for initiating clotting

·        Factors involved in clotting

Essay:

            The fundamental reaction in the clotting of blood is conversion of the soluble plasma protein fibrinogen to insoluble fibrin. The process involves the release of 2 pairs of polypeptides from each fibrinogen molecule. The remaining portion, fibrin monomer, then polymerizes with other monomers to form fibrin. The fibrin is initially a loose mesh of interlacing strands. It is converted by the formation of covalent cross-linkages to a dense, tight aggregate. This latter reaction is catalyzed by factor III, the fibrin-stabilizing factor, and requires Ca²⁺. The conversion of fibrinogen to fibrin is catalyzed by thrombin. Thrombin is a serine protease that is formed from its circulating precursor, prothrombin, by the action of activated factor X. Factor X can be activated by reactions in either of 2 systems, an extrinsic and an intrinsic system. In both the extrinsic and intrinsic pathway a series of different plasma proteins, especially beta-globulins, play major roles. They are called blood-clotting factors and they are inactive forms of proteolytic enzymes. When converted to active forms, their enzymatic actions cause the successive, cascading reactions of the clotting process.

            The extrinsic mechanism for initiating the formation of prothrombin activator begins with a traumatized vascular wall. Traumatized tissue releases a complex of several factors called tissue factor or tissue thromboplasin. This is composed of phospholipids from the membrane of the tissues and a lipoprotein complex containing an important proteolytic enzyme. The lipoprotein complex of tissue factor further complexes with blood coagulation Factor VII and, in the presence of calcium ions, acts enzymatically on Factor X to form activated Factor X. The activated Factor X combines with tissue phospholipids that are part of the tissue factor or with those released from platelets as well as Factor V to form prothrombin activato which splits prothrombin to form thrombin.

            The intrinsic mechanism begins with trauma to the blood itself or exposure of the blood to collagen in a traumatized blood vessel wall. Blood trauma causes activation of Factor XII and release of platelet phospholipids. The activated Factor XII acts enzymatically on Factor XI to activate this as well. This reaction requires high molecular weight kiniogen and is accelerated by prekallikrein. The activated Factor XI then acts enzymatically on Factor IX to activate it. The activated factor IX. acting in concert with activated Factor VIII and with the platelet phospholipids and factor 3 from the traumatized platelets, activates Factor X which then forms prothrombin. This step in the intrinsic pathway is the same as the last step in the extrinsic pathway.

            Rupture of blood vessels causes clotting to be initiated by both pathways simultaneously. Tissue factor initiates the extrinsic pathway, whereas contact of Factor XII and the platelets with collagen in the vascular wall initiates the intrinsic pathway. With severe tissue trauma, clotting can occur in as little as 15 seconds. The intrinsic pathway is much slower to proceed, usually requiring 1 to 6 minutes to cause clotting as it involves more steps.

(a)        Vitamin K is necessary for formation of five of the important clotting factors, prothrombin, Factor VII, Factor IX, Factor X and protein C. In the absence of vitamin K, insufficiency of these coagulation factors can lead to a serious bleeding tendency. Vitamin K is continually synthesized in the intestinal tract by bacteria. In gastrointestinal disease, vitamin K deficiency often occurs as a result of poor absorption of fats from the gastrointestinal tract because vitamin K is fat-soluble and ordinarily absorbed into the blood along with the fats.

(b)        Heparin is a powerful anticoagulant, preventing blood clotting from taking place in the normal vascular system. Heparin is a highly negatively charged conjugated polysaccharide produced mainly by the basophilic mast cells. It combines with antithrombin III and increases its effectiveness in removing thrombin.

(c)            Platelets play many important roles in the blood coagulation process. When a blood vessel is damaged, the platelets first aggregate to form a temporary plug to stem blood loss. This plug is bound together and converted into the definitive clot by fibrin. Platelets are required for the conversion of prothrombin to thrombin. It releases phospholipids which combine with Factor V to form the complex called prothrombin activator which splits prothrombin to form thrombin.