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 f actor XII (FXII), factor XI (FXI), prekallikrein (PK), and high molecu lar weight kininogen (HK) were obtained in immunoassays by comparing w ith control plasma. The plasma levels of FXII and PK were significantl y increased in OC plasma, to 147% and 146% respectively, whereas no si gnificant increase could be registered for FXI (106%) or for HK (107%) . Functional assays carried out with different peptide substrates (S-2 222 for FXIIa, and S-2222, S-2302 and Bz-Pro-Phe-Arg-pNA for kallikrei n) showed increases in OC plasma to about 150% for both proteases, in accordance with results obtained in radial immunodiffusion (RID). Howe ver, when FXIIa was measured with the high molecular weight substrate PK, no significant increase could be registered. Further experiments s uggested this result to be due to the low level of FXI present in OC p lasma, as compared to the levels of FXII and PK. Assays were carried o ut in mixtures of test plasma (OC or control plasma) and plasma defici ent in FXI or FXII. The results obtained suggested that FXIa was prese nt in some kind of association with part of FXIIa and part of kallikre in present. At low concentrations of FXI the functional activity of FX IIa was reduced, and the assay data indicated that an appropriate leve l of FXI was required to obtain maximum rate of hydrolysis of prekalli krein by FXIIa. PKA assays carried out in the presence of lima bean tr ypsin inhibitor (a more potent inhibitor for FXIa than for FXIIa) redu ced the activity of FXIIa in control plasma, but not in OC plasma. Als o experiments carried out with addition of purified FXI supported the suggestion of the significance of FXI for the assay values of FXIIa: T he measured level of FXII was increased in OC plasma, but not in contr ol plasma. At high concentrations of FXI and conditions found to favou r the stability of contact protease association (presence of benzamidi ne), the assay values for both FXIIa and kallikrein were strongly redu ced.