Coagulation can be activated via the intrinsic pathway, so called because its components, factors XII, XI, IX, VIII, prekallikrein, and high molecular weight kininogen, are all plasma proteins located intrinsically inside the lumen of the blood vessel [17]. The intrinsic pathway is activated through a process called contact activation when factor XII undergoes autoactivation to factor XIIa on a negatively charged surface [18]. Negatively charged surfaces include the artifi cial reagents in the APTT assay, such as kaolin, celite and silica, which explains the dependence of the APTT on the contact activation factors. CHAPTER 32 Routine Coagulation Assays 421 Figure 32.1 The elements of the hemostatic system showing the relationship between endothelial cells, the vascular wall, coagulation, coagulation inhibitors, and platelet activation. ECM, extracellular matrix. Extracellular Matrix Proteins Endothelial Cell Procoagulant Platelet Activation Tissue Factor Thrombin Fibrinogen Fibrin Platelet ECM Proteins Fibrinolysis Coagulation Activation Figure 32.2 Diagram of the coagulation cascade depicting the intrinsic and extrinsic pathways of activation.The extrinsic pathway of activation is started with the exposure of tissue factor (TF), coupled with factor VIIa, calcium (Ca ++ ), and phospholipid, that leads to the activation of factor X. The intrinsic pathway is started by the contact activation factors factor XII, high molecular weight kininogen (HMWK), and prekallikrein (PK) with eventual activation of factor X by the tenase complex, which consists of factors IXa, VIIIa, Ca ++ , and phospholipid. Factor IX is also activated by factor VIIa. Activated factor X (Xa) participates in the prothrombinase complex, consisting of factors Xa, Va, Ca ++ , and phospholipids, for the conversion of prothrombin to thrombin, which converts fi brinogen to fi brin monomer. Fibrin then polymerizes and is cross -linked by factor XIIIa. Further activation of coagulation is fostered by the activation of factors V, VIII, and XI by thrombin.