Sensitivity to Activated Protein C; Influence of Oral Contraceptives and Sex

Abstract

SummaryWe investigated sensitivity to activated protein C (APC) in 43 men, 42 women not using oral contraceptives (OC) and 38 women using OC containing 30.0-37.5 μg ethinyl estradiol. A commercially available kit was used. Men were more sensitive to APC as compared with women not using OC (p <0.005), but this difference seems not to be of clinical importance. Women using OC showed to be significantly less sensitive to APC, reflected by a lower APC-ratio, as compared with men (p <0.005) and women not using OC (p <0.05).So, in normal individuals the APC-sensitivity differs according to sex and estrogen intake. This should be taken into account when interpreting APC-ratios.

Acquired APC resistance and oral contraceptives: differences between two functional tests

“…The data presented here, however, show that our plasma collection yields results that are in agreement with earlier publications in which rather small effects of OC use on the aPTT-based APCsr were reported (Henkens et al, 1995;Olivieri et al, 1995;Schramm & Heinemann, 1997).…”

“…Table I summarizes the data together with the results for men and women, separately. In both tests women appeared slightly more resistant to APC than men, confirming earlier reports (De Stefano et al, 1996;Henkens et al, 1995;Koster et al, 1993;Rosing et al, 1997), but only in the ETP-based assay did the gender difference reach statistical significance (P < 0·05, Table I). Fig 2 and Table II summarize the effects of OC use on nAPCsr obtained in both tests for plasmas of normal healthy women who do not carry the factor V Leiden mutation and of women heterozygous for the factor V Leiden mutation.…”

“…Since the effects of oral contraceptives on APC sensitivity ratios determined with other APC-resistance tests appeared to be marginal (Henkens et al, 1995;Olivieri et al, 1995;Schramm & Heinemann, 1997), it was argued (Schramm & Heinemann, 1997) that our earlier observations in the ETP-based assay may have been caused by the selection of OC users or by an ex vivo effect on the plasma collection. The data presented here, however, show that our plasma collection yields results that are in agreement with earlier publications in which rather small effects of OC use on the aPTT-based APCsr were reported (Henkens et al, 1995;Olivieri et al, 1995;Schramm & Heinemann, 1997).…”

“…Acquired APC resistance particularly occurs in plasma of women who use oral contraceptives (Henkens et al, 1995;Olivieri et al, 1995;Rosing et al, 1997) or who are pregnant (Meinardi et al, 1997) and is particularly observed in a functional test in which the ability of APC to down-regulate coagulation is quantitated by measuring its effect on thrombin generation initiated in plasma via the extrinsic pathway .…”

“…However, screening methods that are based on measurement of the effect of APC on the aPTT of undiluted plasma do not fully discriminate between carriers and non-carriers of the factor V Leiden mutation (Engel et al, 1996;Rosen & Sturk, 1997;. In particular, women who are using oral contraceptives (Henkens et al, 1995;Olivieri et al, 1995;Rosing et al, 1997) or who are pregnant (Meinardi et al, 1997) appear to be less sensitive to the anticoagulant action of APC and hence are considered to have acquired APC resistance.…”