Activated protein C resistance and adverse pregnancy outcome

Activated protein C resistance is a genetic disorder that predisposes to thrombosis. Hyperestrogenism strongly increases the risk of thrombosis in affected individuals. Other thrombophilic disorders, such as the antiphospholipid antibody syndrome, have been associated with adverse pregnancy outcome, probably mediated by abnormal clotting in the placental circulation. The purpose of this series is to present clinical and laboratory data on individuals with a poor obstetric history and activated protein C resistance.

Within an 18-month period seven patients with more than five early pregnancy losses, recurrent intrauterine fetal deaths, intrauterine growth restriction, and early severe preeclampsia in association with activated protein C resistance came to our attention. The initial diagnosis was made by activated protein C ratios, and molecular diagnoses of activated protein C resistance genotypes were made by polymerase chain reaction for the factor V Leiden mutation. All patients had an extensive diagnostic workup for known etiologies of the above complications and other thrombophilic disorders.

All patients had activated protein C ratios <1.7. Six patients were heterozygous for the Leiden mutation, and one patient was homozygous. A personal or family history of thromboembolism was present in one case and three cases, respectively. The diagnostic workup was otherwise unrevealing. One newborn was diagnosed of bilateral renal vein thrombosis on day 1 of life.

Activated protein C resistance was found in association with extremely poor obstetric outcomes. A family or personal history of thromboembolism was suggestive in many cases. A population-based study is needed to determine the role of activated protein C resistance in adverse pregnancy outcome.