Mechanism of the participation of the contact system in the Vroman effect. Review and summary

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Abstract
The contact system comprises three zymogens (factor XII, factor XI, and prekallikrein) and the non-enzymatic activation cofactor, high-molecular-weight kininogen (HK). When blood comes into contact with negatively charged surfaces, a small amount of factor XII is adsorbed and activated which, in turn, generates kallikrein from prekallikrein. Kallikrein amplifies the activation of the contact system by producing additional factor Xlla molecules as well as by activating the cofactor, HK, to HKa. HKa, while complexed with either prekallikrein or factor XI, can penetrate a barrier of fibrinogen and adsorb to the surface, where it optimally positions these zymogens for activation by adjacent factor Xlla molecules. Factor Xla can then degrade the light chain of HKa, producing the inactive cofactor HKi, which no longer has the ability to adsorb to a surface or support coagulation. The Vroman effect refers to the ‘conversion’ of fibrinogen from plasma on a negatively charged surface. Fibrinogen is detectable within seconds after normal plasma contacts the surface but, within minutes, is undetectable. On the other hand, HK, although not initially detectable on the surface, is found at later times when fibrinogen is no longer visible. However, in plasma lacking factor XII or HK, fibrinogen remains detectable at times when it is undetectable in normal plasma. The phenomenon of the Vroman effect is explained by the mechanism of surface-dependent activation of factor XII, which both directly and indirectly (through the formation of kallikrein) generates HKa from HK. HKa (but not HK) displaces fibrinogen from the surface. However, if HKa becomes extensively degraded by factor Xla, it loses its ability to displace fibrinogen in the same manner in which it loses its ability to augment contact-activation. Therefore, the Vroman effect reflects the time and surfacedependent generation of HKa, via contact-activation of plasma, which results in the physical displacement of adherent fibrinogen from the surface.