Factors Influencing the Acceleration of Human Factor XIa

Controversy exists in the literature concerning the potentiating effect of heparin on the inactivation rate of factor Xla by antithrombin Ill (AT Ill) in both purified systems and in plasma. We have analyzed the factors that could influence this reaction and found that ionic strength of the medium, as well as the type and concentration of the heparin preparations accounted for the major discrepancies in the literature. At I = 0.43 N, a preparation of bovine lung heparin at 1 U/mL did not augment the inactivation rate of factor Xla by inhibitors in plasma or by purified AT Ill. However, when ionic strength was decreased, a progressive increase in the potentiating effect was observed, reaching 6.5-fold at I = 0.1 5 N. At saturating concentrations of heparin, which results in the formation of 1 00% AT Ill-heparin complex, (> ten-fold molar excess over AT Ill) in purified systems, all heparin preparations (porcine. bovine. low molecular weight [1MW], and high affinity) yielded an -30-fold augmentation of the factor Xla inactivation rate. However, when heparin was less than saturating, we observed that various heparin preparations affected the