Extrinsic coagulation system, activation

At present, the activation of the extrinsic coagulation system is considered to be of more importance in the initiation of DIC than the activation of the contact system (LI2, Cl 3). The activation of the extrinsic system starts with the release of tissue factor (TF) from endothelial cells. TF is a macromolecule, composed of a protein and a lipid fraction, that is synthesized by endothelial cells and monocytes. TF... 

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). 

Activation of the coagulation system may start after activation of the contact factors (intrinsic system) or after release of tissue factor (extrinsic system). 

The intrinsic and extrinsic system paths advance independendy through their initial interactions but eventually follow a common course. The activity of both pathways are important m vivo. The concept of separate systems provides a practical means of evaluating laboratory and clinical coagulation abnormalities. 

An overview of the coagulation cascade and sites of action for coumarins and heparin is shown in A. There are two ways to initiate the cascade (B) 1) conversion of factor XII into its active form (Xlla, intrinsic system) at intravascular sites denuded of endothelium 2) conversion of factor VII into Vila (extrinsic system) under the influence of a tissue-derived lipoprotein (tissue thromboplastin). Both mechanisms converge via factor X into a common final pathway. 

During blood coagulation either an intrinsic (all blood) system or an extrinsic (tissue juice-lipoprotein) system is activated.. In either case the pathways meet at the activation of Factor X, forming a proteolytic enzyme Factor X. This enzyme in the presence of cofactors (calcium ion, phospholipid and Factor V) will form thrombin from prothrombin. Heparin is a cofactor for a protein called antithrombin III which circulates in the plasma and is an inhibitor of both Factor Xg and thrombin. Antithrombin III neutralizes these 2 enzymes by molecular combination heparin increases the rate of this neutralization. In the past 2 years work has continued on the mechanism of blood coagulation More... 

Transient protein C deficiency can be induced when initiating treatment with warfarin because factors VII and protein C have the shortest half-lives of the coagulation factors (Table VII-1-2). Consequently, the extrinsic pathway and protein C system are inactivated, whereas the intrinsic system remains active for a few days. Hypercoagulability occurs (Figure VII-1-2), which may result in dermal vascular thrombosis and skin necrosis. 

Answer C. Warfarin inhibits the hepatic synthesis of factors II (prothrombin), VII, IX, and X. Its onset of anticoagulation activity is slow, and its impact on individual coagulation factors depends on their half-lives. Factor VII and protein C have much shorter half-lives than prothrombin, and so the extrinsic pathway and protein C system are the first to be affected by warfarin. The intrinsic pathway continues to function for 2 to 3 days, causing a state of hypercoagulability with possible vascular thrombosis. 

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