Eighty-one women with a history of thrombosis were classified into three groups: group I (n = 29), women in whom thrombosis developed during oral contraception; group II (n = 33), those who used oral contraceptives (OC) without complications but experienced vascular occlusion in other risk situations; group III (n = 19), women who never used OC. The level of antibodies to anionic phospholipids (PLa), a response to activated protein C (APC), and the presence for the mutation in the coagulation factor V gene causing APC resistance were studied. In the studied groups, APC resistance was present in 14% to 42% of patients. PLa were elevated in about half of APC-resistant patients. The incidence of APC resistance correlated with the recurrency of the thrombotic events within the groups. In most cases it was tightly connected to the mutation in the factor V gene. Women in whom thrombosis developed while they were taking OC (group I) differed from the others, having a remarkable disagreement between the lowest incidence of APC resistance and a relatively increased number of the mutation (14% vs 38%, p < 0.025). This finding suggested that the APC response is flexible. An influence of OC that predisposes a reduction in APC response is discussed.
PIP: In Sweden, clinicians at the Karolinska Hospital in Stockholm interviewed and took blood samples from 81 women aged 18-52 to examine the incidence of an insufficient response to activated protein C (APC), an increased level of antibodies to anionic phospholipids (Pla), and the presence of the mutation in the factor V gene in women who developed thrombosis while using oral contraceptives (OCs), in OC users who developed thrombosis during other risk situations (pregnancy or delivery, surgery, idiopathic), and in non-users who had a history of thrombosis. Women who had thrombosis during OC use had fewer pregnancies before developing thrombosis (p 0.05) and fewer recurrences after the thrombotic event than women in the other two groups. Non-users had the highest proportion of thrombotic recurrences (26%). Pulmonary embolism occurred more often as a result of the thrombotic event during OC use than during pregnancy, delivery, or surgery (p 0.01). APC resistance occurred in 27% of all women. The normalized ACP (nACP) ratio ranged between 0.41 and 1.48. Women who developed thrombosis during OC use had a significantly lower APC resistance than the other two groups (p 0.05). APC resistance increased as did the recurrence of thrombotic events (14-42%). The mean nACP ratio was highest among women who developed thrombosis during OC use and lowest in non-users (0.94 vs. 0.72). 40% of all women had mutation in the factor V gene. All but one woman was heterozygous. This mutation was present in relatively the same proportion in all three groups. The frequency of mutation was greater than that with laboratory-identified APC resistance in women with a history of thrombosis during OC use (38% vs. 14%; p 0.025). Coagulation and genetic analyses were highly correlated (p = 0.001). Pla were present in all three groups at essentially the same levels. Yet lupus anticoagulant activity was more common in OC users who developed thrombosis during other risk situations than the other two groups (p 0.05). 12% of all women had APC resistance and Pla. These findings show a flexible APC response.