1

Figure 36-3

Extrinsic pathway for initiating blood clotting

2. Activation of Factor X—role of Factor VII and tissue factor. The lipoprotein complex of tissue factor further complexes with blood coagulation Factor VII and, in the presence of calcium ions, acts enzymatically on Factor X to form activated Factor X (Xa).

3. Effect of activated Factor X (Xa) to form prothrombin activator—role of Factor V. The activated Factor X combines immediately with tissue phospholipids that are part of tissue factor or with additional phospholipids released from platelets as well as with Factor V to form the complex called prothrombin activator. Within a few seconds, in the presence of calcium ions (Ca++), this splits prothrombin to form thrombin, and the clotting process proceeds as already explained. At first, the Factor V in the prothrombin activator complex is inactive, but once clotting begins and thrombin begins to form, the proteolytic action of thrombin activates Factor V. This then becomes an additional strong accelerator of prothrombin activation. Thus, in the final prothrombin activator complex, activated Factor X is the actual protease that causes splitting of prothrombin to form thrombin; activated Factor V greatly accelerates this protease activity, and platelet phospholipids act as a vehicle that further accelerates the process. Note especially the positive feedback effect of thrombin, acting through Factor V, to accelerate the entire process once it begins.

Intrinsic Pathway for Initiating Clotting

The second mechanism for initiating formation of prothrombin activator, and therefore for initiating clotting, begins with trauma to the blood itself or exposure of the blood to collagen from a traumatized blood vessel wall. Then the process continues through the series of cascading reactions shown in Figure 36-4. 1. Blood trauma causes (1) activation of Factor XII and (2) release of platelet phospholipids. Trauma to the blood or exposure of the blood to vascular

Blood trauma or contact with collagen

(HMW kininogen, prekallikrein)

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Essentials of Human Physiology

Essentials of Human Physiology

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