Is Factor XII Deficiency Related to Recurrent Miscarriage?

Abstract

Factor XII (FXII) is an important protease that plays a major role in the initiation of the intrinsic pathway of blood coagulation. Although congenital FXII deficiency is not associated with a clinical bleeding tendency, it can be identified on a routine coagulation test, such as a prolonged activated partial thromboplastin time. This deficiency is a rare autosomal recessive disorder. It is still unclear whether FXII deficiency causes any disorders during pregnancy. Recurrent miscarriages and placental abruption were reported in cases with FXII deficiency. We successfully treated a woman whose pregnancy was complicated by congenital FXII deficiency. We report her clinical courses of gestation, delivery, and puerperium and discuss the role of maternal FXII associated with pregnancy. In our case, courses of gestation and delivery were normal. Postpartum uterine bleeding was, however, prolonged due to a subinvolution of the puerperal uterus. Our results indicate that, except for postpartum uterine contraction, FXII does not play a major role in gestation and delivery. We suggest that FXII deficiency is not associated with recurrent miscarriage and that normal gestation and vaginal delivery are possible even in cases with congenital FXII deficiency. We assert that the possible correlation of FXII deficiency with recurrent miscarriage merits reevaluation.

Pregnancies and Oral Contraceptive Therapy in Severe (Homozygons) FXII Deficiency: A Study in 12 Patients and Review of the Literature

“…None of our patients showed any undue bleeding at delivery. The same was true for other reports [30]. Five of the propositae have taken oral contraception and no thrombosis has been reported.…”

Recurrent pregnancy loss: the key potential mechanisms

“…Yamada et al also found an increased, but low, prevalence of 2.9% for FXII deficiency in 241 RPL patients [64]. Such low numbers might partly explain conflicting results; indeed, a very recent report suggested no role for FXII deficiency in recurrent miscarriage [65]. Detailed studies of FXII at the molecular level are essential for determining its developmental functions during pregnancy.…”

Autoantibodies to Factor XII and Kininogen‐Dependent Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Pregnancy Loss Augment Platelet Aggregation

“…Gallimore et al 16 reported a high incidence (20.9%) of FXII deficiency in patients who were lupus anticoagulant (LA) positive. 18 Recently, Pauer et al 19 generated mice deficient in FXII using a gene-targeting approach. They studied plasma samples from LA positive patients for the presence of anti-FXII and reported that many patients were positive for anti-FXII detected by ELISA and surface plasmon resonance.…”