Management and Outcomes of Pregnancy and Childbirth in Known and Unknown Hemophilia Carriers: 10 Years Retrospective Evaluation from Southern Italy

Women carriers of hemophilia (HC) or affected by haemophilia (HW) are often asymptomatic, but they may experience bleeding, in particular during menses, pregnancy, childbirth, and the postpartum period, conditions where management may be particularly challenging if HC status is unknown or not adequately addressed before. Data regarding the correlation between bleeding symptoms and coagulation FVIII/FIX levels in HCs are conflicting; mainly due to considerable phenotypic variability. There are no specific guidelines, scientific societies still debate on the optimal mode of delivery and possible treatment options

AIM

This retrospective, observational study, conducted in Italy in 2022, aims to describe how known and unknown HC were managed during pregnancy and delivery, by evaluating clinical, laboratory parameters and the need for any replacement therapy (RT). The study aims to collect data to understand the most commonly adopted diagnostic and therapeutic measures for women with hemophilia during pregnancy, childbirth, and postpartum

METHODS

This study is national, and we here report the analysis performed on two regions of Southern Italy , in detail from two Haemophilia Centers in Palermo and Catanzaro. Following the approval of the Ethics Committee, HC were enrolled through Informed Consent from January 2022 to December 2022. HC and HW were defined according to the new nomenclature from ISTH. The following data were collected: age, ISTH bleeding score, genetic testing, complete blood cell count, age of menarche, awareness of HC status and age of diagnosis, prenatal diagnosis, number of pregnancies, type of delivery, FVIII and FIX levels, post-partum bleeding, and pregnancy-related complications

RESULTS

Twenty women were recruited, median age 37 y.o (22;48), at diagnosis 30 y.o (18;41), 13 from Palermo and 7 from Catanzaro, totaling 11 HC and 6 HW with Hemophilia A and 2 HC and 1 HW with Hemophilia B. The hemorrhages reported were secondary to abnormal menstrual blood loss (9/20; 45%) and the postpartum period. Data were collected on 48 pregnancies, mean 2.4 (1;5), delivered to term with a total of 36 vaginal deliveries and 12 cesarean deliveries. HC status was previously known only in 4 of the 20 women. Delivery and postpartum bleeding requiring medical intervention (pRBC transfusions and antifibrinolytic agents) was observed in 2(15%) HC and 3(43%)HW. Contrasting data were found when comparing the two centers’ populations. In Palermo’s cohort delivery and postpartum bleeding was observed in 2(20%) HC and 1(33%) HW. In the cohort from Catanzaro delivery and postpartum bleeding was observed in 0 HC and 2(50%) HW. Peripartum anesthesia was performed in 24(50%) deliveries. Episiotomy was performed in 13(27%) deliveries. No significant differences were observed between HC and HW regarding the incidence of bleeding. However, a difference between the two centers was observed: incidence of hemorrhages was different in Palermo, where HC experienced more hemorrhages during pregnancy and postpartum than HW, while in Catanzaro, HW experienced more bleeding than HC. A single HC enrolled with a BMI>30 and FVIII/IX levels above 100% had a higher incidence of bleeding compared to other HC and HW, presenting severe hemorrhages that require treatment. In women with more than one pregnancy, the management did not change after the discovery of their HC status. Interestingly 17 women out of 20 were managed outside their referral haemophilia centers and haematologist was not consulted. Only 3 women were followed during pregnancy; prenatal diagnosis was not performed, but in agreement with the gynecologist, deliveries were managed a cesarean section to avoid a potential instrumental delivery

DISCUSSION

The management of HC and HW during pregnancy and childbirth in the last ten years is quite variable, however pregnancy related complications occur in a not neglegible number of patients, this mirrors the absence of specific guidance on haemophilia and the still extremely low rate of diagnosis of carrier status, leading to the consideration that several factors, including cultural barriers, affect women with a rare disease

CONCLUSIONS

HC status is a still inadequately addressed condition, a more accurate report of pregnancy outcomes in HC is needed, a multicenter Italian study on this issue is currently ongoing,this will also contribute to unreveal cultural burdens between different areas of the Nation