Contributions of contact activation pathways of coagulation factor XII in plasma.
Activation of human blood plasma coagulation by contact with hydrophilic or hydrophobic surfaces (procoagulants) is dominated by kallikrein (Kal)-mediated activation of the blood zymogen FXII (Hageman Factor). Mathematical modeling of prekallikrein (PK)-deficient platelet-poor plasma (d(PK)PPP) and PK-reconstituted d(PK)PPP (Rd(PK)PPP) coagulation shows that autoactivation of FXII (FXII-->[surface]FXII) produces no more than about 25% of the total FXIIa produced by the intrinsic pathway. Autoactivation and reciprocal-activation increase in the same proportion with procoagulant surface energy (water-wettability), whereas total amount of FXIIa produced per-unit-area procoagulant remains roughly constant for any particular procoagulant. These results suggest that procoagulant surfaces initiate the intrinsic cascade by producing a bolus of FXIIa in proportion to surface energy or surface area but play no additional role in subsequent molecular events in the cascade. Results further suggest that reciprocal-activation occurs in proportion to the amount of FXIIa produced by the initiating autoactivation step.
Chatterjee
Kaushik
K
Department of Bioengineering, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Guo
Zhe
Z
Vogler
Erwin A
EA
Siedlecki
Christopher A
CA
D001777:Blood Coagulation / Q000502:physiology; D005174:Factor XII / Q000378:metabolism*; D005175:Factor XII Deficiency; D015956:Factor XIIa / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010949:Plasma / Q000378:metabolism*; D011288:Prekallikrein / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013499:Surface Properties; D017155:Wettability
D005174:Factor XII; D011288:Prekallikrein; D015956:Factor XIIa