Gynecological and obstetric outcome in the French cohort of women with factor XIII deficiency

Abstract

Introduction: Congenital factor XIII deficiency is a very rare bleeding disorder affecting 33 patients in France. Besides its role in fibrin clot stabilization, factor XIII is involved in placental attachment. Fetal miscarriages represent a frequent and concerning issue for these patients. The aim of the present study was to describe clinical characteristics of women presenting severe congenital FXIII deficiency in France, to focus on gynecological and obstetrical events, and to report the management of these rare situations. Methods: We conducted a retrospective study in the French Hemophilia Comprehensive Care and Clinical Hemostasis Centers. Women between 15 and 65 years with factor XIII activity <10 IU dL − 1 were included. Biological, clinical and therapeutic events that occurred to these patients during their gynecological and obstetrical period were recorded. Results: Among 31 centers, eleven patients were included. The median age at diagnosis was 1.5 years (range: 0-35), and at inclusion it was 30 years (range: 15-63). Fetal miscarriage was the primary manifestations in 2 (18%) patients, the remaining were diagnosed during hemorrhage. Menorrhagias were reported by 2 women (27%), 13 pregnancies were reported by 9 women including one abortion. Every pregnancy was conducted under factor XIII substitution, no hemorrhagic episode was reported. Four patients (36%) experienced at least one fetal miscarriage with a total amount of 30 miscarriages with 6 occurring during substitution. Conclusion: Altogether, our data confirmed the high incidence of miscarriage in women with factor XIII deficiency. Good outcome of pregnancies required prophylaxis in accordance with international guidelines.

Challenges Regarding the Management of Gynecological and Obstetric Complications in Women with Inherited Factor XIII Deficiency

“…Regarding miscarriages, Sharief et al report that, in 121 women with FXIIID, the risk of miscarriages was very high, nearly 70% [20]. Without FXIII substitution, the frequency of pregnancy with birth of a healthy infant was estimated to be 10%, and miscarriages occurred mainly during the first trimester [20]; a high risk of miscarriage was also the main feature of pregnancies in women with FXIIID in the French study: 30 miscarriages in 4 patients, including 12 in one patient who did not receive FXIII substitution before or during pregnancies [21], and 97% of these miscarriages occurred during the first trimester. These results are similar to those published by Naderi et al who reported 17 cases in Iran [7].…”

“…In the French study previously mentioned, 11 pregnancies conducted under the administration of pdFXIII doses ranging from 400 to 800 IU per week throughout the pregnancy had a good outcome [21]; and increasing doses were prescribed during 3 pregnancies. These results suggest that at least one infusion of 400 IU per week of pdFXIII could lead to safe child birth [21].…”

“…Regarding menorrhagia in these patients, the RBDs Database international registry reports menometrorrhagia in women with levels of FXIII around 2.6 IU dL -1 (0-23.7 IU dL -1 ) [5]. A retrospective French series conducted in 11 women provided the largest series from Western countries of gynecological issues in patients with severe FXIIID (levels < 10 IU dL -1 ) [21]. In this series, only 2 of the 11 patients (18%) under prophylaxis reported menorrhagia, whereas 3 (27%) women reported not experiencing menorrhagia before initiating treatment; no life-threatening peritoneal bleeding was observed [21].…”

“…A retrospective French series conducted in 11 women provided the largest series from Western countries of gynecological issues in patients with severe FXIIID (levels < 10 IU dL -1 ) [21]. In this series, only 2 of the 11 patients (18%) under prophylaxis reported menorrhagia, whereas 3 (27%) women reported not experiencing menorrhagia before initiating treatment; no life-threatening peritoneal bleeding was observed [21]. The low rate of gynecological bleeding could be explained by the long-term prophylaxis treatment received by the patients; for example, in women without prophylaxis, the occurrence of menorrhagia reported ranges from 35% in 20 women in the series from Iran [22] to 63% in 11 women in a review [23]; a larger systematic review, however, found that only 31 (26%) of 121 women described with FXIIID, presented menorrhagia or heavy menstrual bleeding (HMB), and peritoneal bleeding due to ruptured ovarian cyst was reported in 10 (10%) women [20].…”

“…Other authors have advocated for the use of 250 FXIII IU per week from the beginning of the pregnancy until the 6 th month, followed by 500 IU per week and an additional dose of 1000 IU at the time of delivery [30,31]. In the French study previously mentioned, 11 pregnancies conducted under the administration of pdFXIII doses ranging from 400 to 800 IU per week throughout the pregnancy had a good outcome [21]; and increasing doses were prescribed during 3 pregnancies. These results suggest that at least one infusion of 400 IU per week of pdFXIII could lead to safe child birth [21].…”