VARIABILITY OF THE RESPONSE TO ACTIVATED PROTEIN-C DURING NORMAL-PREGNANCY

The response to activated protein C (APC) was investigated in 28 healt hy women, non-carriers of the Arg(506)-Gln mutation in factor V, throu ghout pregnancy (gestation weeks 12, 20, 28, 32 and 37) and after the delivery. A suppression of APC response was observed which reached low est values by week 28 (nAPC-ratio 0.78 +/- 0.13), sustained low up to the end of pregnancy and rose after delivery (1.11 +/- 0.22; P < 0.05) . APC resistance (nAPC ratio < 0.75) was registered in 16 of the 28 wo men (57%). A reduction of APC ratio was directly related to its value in the non-pregnant state, being most pronounced in the women with the highest APC ratio. Factor VIII increased during pregnancy and correla ted inversely to APC ratio (Z coefficient = -0.645, P<0.0001). The cor relation became weaker in the course of pregnancy, losing significance by week 32. This was explained by the difference in profiles of the t wo variables: the lowest measured APC ratio preceded the peak of facto r VIII in most cases. The most pronounced rise of factor VIII was foun d in the women with minimal levels of APC ratio between 0.8 and 0.7. T hese results allowed us to speculate that APC response is closely regu lated during pregnancy, aiming to maintain a certain relevant level. T ransitory reduction of APC response is connected to factor VIII and di scussed as a prevalent mechanism of functional APC resistance during p regnancy.