**3. Pathophysiology**

The coagulation cascade is a complex system in which multiple components are activated to produce fibrin. An overview of the system along with the targets of various therapeutic interventions is shown in Figure 1. The coagulation pathway is separated into the intrinsic and the extrinsic pathways. The latter is activated in response to specific tissue injury. Both lead to the eventual formation of thrombin. Thrombin causes the conversion of fibrinogen to fibrin. Additionally, it activates factor XIII which stabilizes the fibrin. An endogenous fibrinolytic system balances this system. It consists of antithrombins, proteins C and S, and the plasmin-plasminogen system.

Fig. 1. Targets for anticoagulant drugs. LMWH = low-molecular-weight heparin. (Reference: Hoffman M, Dougald M. The action of high-dose factor VIIa in a cell-based model of hemostasis. *Disease a Month* 2003; 49: 14-21)

The primary pathophysiology factors that predispose any patient to VTE are the Virchow's Triad: endothelial injury, venous stasis (or turbulent blood flow), and hypercoagulability. Endothelial injury can occur due to manipulation, and retractor placement during surgery. Venous stasis can occur due to positioning and the use of a tourniquet. Hypercoagulability can occur as a result of depletion or dilution of endogenous anticoagulants. It is also associated with several pro-coagulant disease processes such as factor V Leiden deficiency, protein C and S deficiency, and others.
