Blood coagulation involves a biological amplification system in which relatively few initiation substances sequentially activate by proteolysis a cascade of circulating precursors proteins (the coagulation factor enzymes) which culminate in the generation of thrombin, this in turn, converts soluble plasma fibrinogen into fibrin. Blood coagulation involves a biological amplification system in which relatively few initiation substances sequentially activate by proteolysis a cascade of circulating precursors proteins (the coagulation factor enzymes) which culminate in the generation of thrombin, this in turn, converts soluble plasma fibrinogen into fibrin. Fibrin catches or traps the platelets aggregation at the side of the injury and converts the unstable primary platelet plug to firm and solid, definite and staple haemostatic plug. Fibrin catches or traps the platelets aggregation at the side of the injury and converts the unstable primary platelet plug to firm and solid, definite and staple haemostatic plug.

Active form. Descriptive name. Factor number. Fibrin subunit FibrinogenI Serine protease ProthrombinII Receptor/ Cofactor. Tissue factor III Cofactor Labile factor V Serine protease ProconvertinVII Cofactor Antihaemophilic factor VIII Serine protease Christmas factor IX Serine protease Stuart-Prower factor. X Serine protease Plasma thromboplastin antecedent XI Serine protease Hageman (contact factor) XII Transglutaminase Fibrin stabilizing factor. XIII Serine protease Prekallikrein ( Fletcher factor) - cofactor High Molecular Weight Kininogen (HMWK). -

Factor VIII is pound in plasma to VWF. It is synthesized in the liver may be by the hepatocytes. Factor VIII is pound in plasma to VWF. It is synthesized in the liver may be by the hepatocytes. The factors I, V, VIII, XI and XII increase in inflammation, pregnancy and oral contraceptives. Thrombin interacts with them. The factors I, V, VIII, XI and XII increase in inflammation, pregnancy and oral contraceptives. Thrombin interacts with them. Vitamiin-K-dependent coagulation proteins: Clotting factors II, VII, IX and X (Procoagulant), also PC and PS (anticoagulants) are called also the Prothrombin group, vitamin K needed for synthesis, required Ca 2+ for activation and are stable factors, all synthesized by the liver. Vitamiin-K-dependent coagulation proteins: Clotting factors II, VII, IX and X (Procoagulant), also PC and PS (anticoagulants) are called also the Prothrombin group, vitamin K needed for synthesis, required Ca 2+ for activation and are stable factors, all synthesized by the liver.

Contact factor are XII, Prekallikrein and High Molecular Weight Kininogen (HMWK). They produce by the liver. XII can be non- enzymatically activated by contact with collagen fibers and other negatively charged surfaces. Contact factor are XII, Prekallikrein and High Molecular Weight Kininogen (HMWK). They produce by the liver. XII can be non- enzymatically activated by contact with collagen fibers and other negatively charged surfaces. Thrombin-sensitive coagulation proteins: these are fibrinogen, XIII, V and VIII protein complex. Thrombin-sensitive coagulation proteins: these are fibrinogen, XIII, V and VIII protein complex.

The operation of these enzyme cascade requires local concentration of circulating coagulation Factors At the site of the injury. The operation of these enzyme cascade requires local concentration of circulating coagulation Factors At the site of the injury. Surface-mediated reactions occur on exposed collagen, platelet phospholipids and tissue factor. Surface-mediated reactions occur on exposed collagen, platelet phospholipids and tissue factor. Although it has been traditional (and useful for in vitro laboratory testing) to divide the coagulation system into intrinsic and extrinsic pathways, such a division does not occur in vivo because tissue factor- factor VIIa complex is a potent activator of both factor IX and factor X. Although it has been traditional (and useful for in vitro laboratory testing) to divide the coagulation system into intrinsic and extrinsic pathways, such a division does not occur in vivo because tissue factor- factor VIIa complex is a potent activator of both factor IX and factor X.

Coagulation begins when tissue factor activated on the surface of injured cells binds and activates factor VII: the complex activates factor IX which, with cofactor VIII. Activates factor X to Xa. Coagulation begins when tissue factor activated on the surface of injured cells binds and activates factor VII: the complex activates factor IX which, with cofactor VIII. Activates factor X to Xa. Platelets accelerate the coagulation process by providing membrane phospholipid. Platelets accelerate the coagulation process by providing membrane phospholipid.

The complex of Xa and Va, activated from cofactor V acts on prothrombin (factor II) to generate thrombin. The complex of Xa and Va, activated from cofactor V acts on prothrombin (factor II) to generate thrombin. Thrombin then converts fibrinogen into fibrin monomers, which are able to polymerize non-enzymatically and become a gel. Thrombin then converts fibrinogen into fibrin monomers, which are able to polymerize non-enzymatically and become a gel. This early fibrin clot is relatively solubilized and digested by the fibrinolytic system. A tough insoluble fibrin colt is formed after interaction with factor XIII. This early fibrin clot is relatively solubilized and digested by the fibrinolytic system. A tough insoluble fibrin colt is formed after interaction with factor XIII.

Factor VIII protein complex (factor VIII:C) consists of two proteins: factor VIII procoagulant protein and vWF. Factor VIII protein complex (factor VIII:C) consists of two proteins: factor VIII procoagulant protein and vWF. Factor VIII:C and vWF (the last makes up over 99% of the complex) circulate in plasma as a complex and probably stabilize and protect each other. Factor VIII:C and vWF (the last makes up over 99% of the complex) circulate in plasma as a complex and probably stabilize and protect each other.

Coagulation cascade:1-2 1 Injury initiates release of tissue factor (TF).which binds and activates factor VII. Injury initiates release of tissue factor (TF).which binds and activates factor VII. Tie TF VIIa complex activates factors X and IX. Tie TF VIIa complex activates factors X and IX. The activity of the TF VIIa complex is inhibited by T F pathway inhibitor (T FPI ). The activity of the TF VIIa complex is inhibited by T F pathway inhibitor (T FPI ). The VIIIa-IXa complex amplifies Xa production from X. The VIIIa-IXa complex amplifies Xa production from X. Thrombin is generated from prothrombin by the action of Xa-Va complex leads to fibrin clot formation. Thrombin is generated from prothrombin by the action of Xa-Va complex leads to fibrin clot formation.

Thrombin also: Thrombin also: Activates XI leading to increased IXa production. Activates XI leading to increased IXa production. Cleaves VIII from its carrier protein vWF activating VIII. Cleaves VIII from its carrier protein vWF activating VIII. Activates V to Va. Activates V to Va. Activates XIII to XIIIa, which stabilizes the fibrin clot. Activates XIII to XIIIa, which stabilizes the fibrin clot.

Note that: TFPI inhibits TF/VIIa, and Xa. TFPI inhibits TF/VIIa, and Xa. Activated PC and PS will inhibit Va and VIII. Activated PC and PS will inhibit Va and VIII. Antihrombin inhibits thrombin, Xa, IXa. Antihrombin inhibits thrombin, Xa, IXa. Extrinsic pathway: Factor VII. Extrinsic pathway: Factor VII. Intrinsic pathway: Factors XI, IX, VIII. Intrinsic pathway: Factors XI, IX, VIII. Common pathway: Factors X, V, II and fibrinogen. Common pathway: Factors X, V, II and fibrinogen. Factor XIII crosslink the polymer to form a more stable clot. Factor XIII crosslink the polymer to form a more stable clot.

Thrombin has a number of key rules in the coagulation process: Thrombin has a number of key rules in the coagulation process: It converts plasma fibrinogen into fibrin. It converts plasma fibrinogen into fibrin. It amplifies coagulation by: Activating factor XI which increases IXa production. Activating factor XI which increases IXa production. Cleaving factor VIII from its carrier molecule vWF to activate it and augment Xa pro ­ duction. Cleaving factor VIII from its carrier molecule vWF to activate it and augment Xa pro ­ duction.

Activating factor V to factor Va. Activating factor V to factor Va. It activates factor XIII to factor XIII in. which stabilizes the fibrin clot. It activates factor XIII to factor XIII in. which stabilizes the fibrin clot. It potentates platelet aggregation. It potentates platelet aggregation. It hinds to thrombomodulin on the endothelial cell surface to form a complex which activates protein C, which is involved in regulating coagulation. It hinds to thrombomodulin on the endothelial cell surface to form a complex which activates protein C, which is involved in regulating coagulation.