ACQUIRED APC RESISTANCE RELATED TO ORAL CONTRACEPTIVES AND PREGNANCY AND ITS POSSIBLE IMPLICATIONS FOR CLINICAL PRACTICE

Hereditary activated protein C (APC) resistance is an established risk factor for venous thromboembolism and a decreased sensitivity to APC is widely used to identify carriers of this mutation. The authors demonstrated differences in APC sensitivity between healthy men and women especially oral contraceptive (OC) users. To confirm an estrogen-related hormonal effect on acquired APC resistance the study was extended to healthy pregnant women. APC values obtained from 38 women at 36 weeks gestation were compared with those previously obtained in 43 healthy men 38 OC users and 42 women not using OCs. Values below the lower limit of the normal range (0.82-1.22) were found in 10% of nonusers of OCs 32% of OC users and 82% of pregnant women compared with 5% of men. The standard APR resistance test yielded false-positive results in 25% of OC users and 75% of pregnant women. When the modified sensitivity ratio was used there was no significant difference between pregnant women and men and lowered values were found in 5% of each of the study groups. Increased levels of fibrinogen and factors II VIII IX and X experienced during pregnancy and OC use could explain a lowered APC ratio by shortening the partial thromboplastin time. Clinical studies are recommended to assess the contribution of acquired APC resistance to the development of thrombosis in pregnant women and OC users either as an independent or concomitant risk factor.