Chapter 4: Hemostasis and Coagulation
Which of the following is true regarding the intrinsic and extrinsic coagulation pathways?
(A) In the classic model of coagulation, the extrinsic pathway initiates coagulation by interaction of circulating factors already within the blood.
(B) In the classic model of coagulation, the intrinsic pathway initiates coagulation by interaction with subendothelial tissue factor.
(C) Defects in the intrinsic pathway lead to elevations of the activated partial thromboplastin time (aPTT).
(D) Defects in the intrinsic pathway lead to elevations of the prothrombin time (PT).
(E) The intrinsic pathway requires the presence of factor VII and Ca2+.
(C) Older textbooks divide the coagulation cascade into the intrinsic and extrinsic pathways. This traditional depiction is useful in interpreting coagulation test abnormalities, such as PT and aPTT. The intrinsic pathway can be activated without an extravascular source. The extrinsic pathway, in contrast, requires an extravascular component, such as tissue factor (TF), for activation. Both pathways are thought to be activated simultaneously to initiate and sustain clot formation (Fig. 4-10).
FIGURE 4-10. Schematic representation of the traditional coagulation scheme or “waterfall hypothesis.”
Elevations in the aPTT arise from defects in the intrinsic pathway. This pathway begins with trauma to the blood vessel and exposure of blood to collagen in a damaged vascular wall, but as the name implies, it can also occur outside the vascular wall with most “wettable” surfaces, such as tables and glass. In response to these stimuli, factor XII (Hageman factor) is activated to form factor XIIa. Activated factor XII then activates factor XI to factor XIa. Activated factor XI converts factor IX to factor IXa. Factor IXa then converts factor X to factor Xa. This activation of factor X is also greatly accelerated by factor VIIIa. Activated factor X converts the inactive molecule prothrombin to the active thrombin.
Elevations in the PT arise from defects in the extrinsic pathway. This pathway requires either a vascular wall to be penetrated or the presence of extravascular tissue. TF is found predominantly on most nonendothelial cells. Damage to vessel walls causes the plasma to be exposed to TF. TF combines with factor VII to form the TF-VIIa complex. TF-VIIa complex in the presence of Ca2+ and phospholipids can activate factor X to Xa, leading to thrombin formation.
Once thrombin has formed, it has numerous other jobs, including cleaving fibrinogen into the fibrin monomers. Fibrin monomers consist of fibrinopeptides A and B, which each undergo conformational changes to expose the active components and allow for polymerization. Polymerization of fibrin occurs by cross-linking ...