Contact factors in plasma from women on oral contraception - Significance of factor XI for the measured activity of factor XII

The plasma levels of contact activation factors were measured in women using a low estrogen dose oral contraceptive (OC). Basic values for factor XII (FXII), factor XI (FXI), prekallikrein (PK), and high molecular weight kininogen (HK) were obtained in immunoassays by comparing with control plasma. The plasma levels of FXII and PK were significantly increased in OC plasma, to 147% and 146% respectively, whereas no significant increase could be registered for FXI (106%) or for HK (107%). Functional assays carried out with different peptide substrates (S-2222 for FXIIa, and S-2222, S-2302 and Bz-Pro-Phe-Arg-pNA for kallikrein) showed increases in OC plasma to about 150% for both proteases, in accordance with results obtained in radial immunodiffusion (RID). However, when FXIIa was measured with the high molecular weight substrate PK, no significant increase could be registered. Further experiments suggested this result to be due to the low level of FXI present in OC plasma, as compared to the levels of FXII and PK. Assays were carried out in mixtures of test plasma (OC or control plasma) and plasma deficient in FXI or FXII. The results obtained suggested that FXIa was present in some kind of association with part of FXIIa and part of kallikrein present. At low concentrations of FXI the functional activity of FXIIa was reduced, and the assay data indicated that an appropriate level of FXI was required to obtain maximum rate of hydrolysis of prekallikrein by FXIIa. PKA assays carried out in the presence of lima bean trypsin inhibitor (a more potent inhibitor for FXIa than for FXIIa) reduced the activity of FXIIa in control plasma, but not in OC plasma. Also experiments carried out with addition of purified FXI supported the suggestion of the significance of FXI for the assay values of FXIIa: The measured level of FXII was increased in OC plasma, but not in control plasma. At high concentrations of FXI and conditions found to favour the stability of contact protease association (presence of benzamidine), the assay values for both FXIIa and kallikrein were strongly reduced.