Effect of Heparin on the Inactivation Rate of Human Activated Factor XII by Antithrombin

Human antithrombin Ill (ATIII) is a plasma inhibitor of several serine proteases of the blood coagulation system. Previous investigations have reported that the presence of heparin has a multifold accelerating effect on the inhibition of factor Xlla and Xllf, the active species derived from factor XII. Recent studies from our laboratories have confirmed that ATIII inactivates factor XIla and factor Xllf, but only contributes 2% to 3% to the inhibition of activated factor XII species in plasma. The major inhibitor is Cl inhibitor. Therefore, we have reexamined the heparin effect on the rate of inhibition of factor XIIa and factor Xllf in purified systems. We also have studied the effect of heparin on the inactivation of both factor XlI-derived active species by various plasmas. Using purified factor XlIa and ATIII, we found that heparin (0.7 to 34.0 U/mL) increased the rate of inhibition of Factor XIIa. However, at heparin concentrations usually achieved during anticoagulant therapy (0.7 U/mI), the inhibition was accelerated only fourfold. This implies only a 6% contribution to the inhibitory