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J Intern Med. 1998 Jul;244(1):27-32.

Resistance to activated protein C, highly prevalent amongst users of oral contraceptives with venous thromboembolism.

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Medicinkliniken, Blekinge Hospital, Karlskrona, Sweden.



Inherited resistance to activated protein C (APC resistance), which is caused by a single point mutation in the factor V gene, is a frequent risk factor for venous thromboembolism. The aim of this study was to determine the prevalence of APC resistance and other coagulation disorders in fertile women with venous thromboembolism and also the risk factors these women had been exposed to in connection with thromboembolic events.


A retrospective, case-control study of 36 month duration.


The study was carried out at Blekinge Hospital, Karlskrona, Sweden.


The study population comprised 27 fertile women age 16-47 years with thromboembolic complications, referred to the department of Internal Medicine at Blekinge Hospital in Karlskrona during a 36-month period.


APC resistance was found in 10 out of 27 women. APC resistance was associated with treatment with oral contraceptives in five out of six women and with pregnancy in one of seven women. All women with resistance to APC developed venous thrombosis in association with a predisposing situation (risk situation) such as surgery, trauma, immobilization, pregnancy, inflammatory state or the use of oral contraceptives. Amongst women not resistant to APC, all but one developed thrombosis in connection with a risk situation.


APC resistance was found to be highly prevalent amongst fertile women with a history of thromboembolic complication occurring during their use of oral contraceptives.


Resistance to activated protein C (APC), caused by a single point mutation in the factor V gene, is a significant risk factor for venous thromboembolism. Studies conducted in Sweden have found prevalences of APC resistance ranging from 7% to 15%. The prevalence of this and other risk factors was investigated retrospectively in 27 fertile women 16-47 years of age admitted to Blekinge Hospital (Karlskrona, Sweden) with venous thromboembolism during a 36-month period (1992-94). APC resistance was detected in 10 (37%) of these women, 7 of whom had a family history of venous thrombosis. All 10 women with APC resistance had been exposed to at least one other risk factor. Oral contraceptive (OC) use was reported by 5 women in the APC resistance group and by 1 non-APC resistant case; 5 of these OC users took a pill containing desogestrel. 7 women with venous thromboembolism (1 in the APC-resistant group) were pregnant or postpartum. Other risk factors included surgery (n = 5) and pregnancy-related immobilization (n = 4).

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