Extrinsic pathway of coagulation

The extrinsic pathway of coagulation is activated when circulating factor VII encounters tissue factor. Tissue factor is a transmembrane glycoprotein, which is normally expressed by subendothelial fibroblast-like cells, which surround the blood vessel. An intact endothelium normally shields the circulating blood from exposure to tissue factor. The tissue factor molecule consists of a 219 amino acid hydrophilic extracellular domain, a 23 amino acid hydrophobic region that spans the membrane, and a 21 amino acid cytoplasmic tail that anchors the molecule to the cell membrane (15,16). Other sites of tissue factor expression include activated monocytes, activated endothelial cells, and atherosclerotic plaques. 

Rao, K.W.M. 1987. Studies of mechanisms inhibiting the initiation of extrinsic pathway of coagulation. Blood 69 645-651. 

Factor X is a plasma protein involved in both the intrinsic and extrinsic pathways of blood coagulation. Factor X has a mass of 55kDa and the activated Xa of 40kDa. The normal concentration in plasma is 6-8 pg/ml. Post-translational modifications of the protein involve y-carboxylation of specific glutamic acid residues, 3-hydroxylation of one aspartic acid residue, and N- and 0-linked glycosylation. 

Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vase Biol 2007 27(8) 1687-93. 

Lipids play an essential role in both the intrinsic and extrinsic pathways of proArombin activation. They enter the coagulation sequence after it has been initiated by surface contact and other protein interactions. There is no evidence that they initiate the coagulation process. The lipid is normally derived from the blood platelet where it probably exists as lipoprotein. It exerts a surface catalytic action on the plasma coagulation proteins with which it may bind in the presence of calciiun. The resulting complex could contain platelet liproprotein or its lipid moiety alone and may mediate prothrombin activation. 

Extrinsic Pathway. Coagulation is initiated when tissue extracts with Hpid—protein properties are released from the membranes of endothehal cells following injury or insult. These substances, collectively designated tissue thromboplastin, complex with circulating Factor VII and in the presence of calcium ions subsequentiy activate Factor X (Fig. 1). In vitro evidence suggests that Factor X can be activated less rapidly through the interaction of kaUikrein [9001-01-8] with Factor VII. 

Figure 51-1. The pathways of blood coagulation. The intrinsic and extrinsic pathways are indicated. The events depicted below factor Xa are designated the final common pathway, culminating in the formation of cross-linked fibrin. New observations (dotted arrow) include the finding that complexes of tissue factor and factor Vila activate not only factor X (in the classic extrinsic pathway) but also factor IX in the intrinsic pathway, in addition, thrombin and factor Xa feedback-activate at the two sites indicated (dashed arrows). (PK, prekallikrein HK, HMW kininogen PL, phospholipids.) (Reproduced, with permission, from Roberts HR, Lozier JN New perspectives on the coagulation cascade. Hosp Pract [Off Ed] 1992Jan 27 97.)...

The coagulation system that generates thrombin consists of intrinsic and extrinsic pathways. Both pathways are composed of a series of enzymatic reactions eventually producing thrombin, fibrin, and a stable clot. In parallel with the coagulation, the fibrinolytic system is activated locally. Plasminogen is converted to plasmin, which dissolves the fibrin mesh1 2 3 (Fig. 64—1). 

Two coagulation factors function uniquely in the extrinsic pathway factor III (tissue factor) and factor VII. Tissue factor is an integral membrane protein present in a wide variety of tissue types (particularly lung and brain). This protein is exposed to blood constituents only upon rupture of... 

Extrinsic pathway Coagulation is activated by release of tissue thromboplastin, a factor not found in circulating blood. Clotting occurs in seconds because factor III bypasses the early reactions. 

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