RESISTANCE TO ACTIVATED PROTEIN-C IN HEALTHY WOMEN TAKING ORAL-CONTRACEPTIVES

Resistance to activated protein C (APC) is at present considered the m ost frequent laboratory abnormality in patients with deep-vein thrombo sis. An increased risk for venous thrombosis is associated to the use of oral contraceptives (OC). We studied APC sensitivity in 50 healthy women taking OC and in 50 healthy controls, matched for age, smoking h abit, educational and social levels, and the main biochemical routinar y parameters. Subjects with a personal or familial history of thrombos is and also with chronic or acute diseases were excluded. Protein C, p rotein S, antithrombin III and lupus anticoagulant activity (LAG) were also evaluated. Increased fibrinogen and protein C levels, decreased protein S, and shortened PT and APTT were also observed in women takin g OC. APC sensitivity ratio (APC-SR) was significantly lower in the OC group than in a control group (2.6 +/- 0.38 v 2.81 +/- 0.35, P < 0.01 ). Seven of eight women with APC ratio less than or equal to 2 (APC re sistant) were OC users: the difference of prevalence was statistically significant (chi-squared test, P < 0.05). Only two out of eight women were found heterozygous for the Leiden factor V mutation. Two APC-res istant women without the Leiden mutation subsequently discontinued OC and both then normalized their APC-SR. We conclude that acquired facto rs, i.e. oral contraceptives, may play an important role in determinin g plasma APC resistance.