Menstrual and obstetrical bleeding in women with inherited platelet receptor defects-A systematic review.

INTRODUCTION: Women with inherited platelet receptor defects (IPRD) may have an increased risk of heavy menstrual bleeding (HMB) and postpartum haemorrhage (PPH). AIM: To present a systematic overview of the literature on the prevalence and management of menstrual and obstetrical bleeding in women with IPRD. METHODS: Electronic databases were searched for original patient data on the prevalence and management of HMB and PPH in women with known IPRD or who were being investigated for IPRD. RESULTS: Sixty-nine papers (61 case reports/series and 8 cohort studies) were included. Overall, studies were rated as 'poor quality'. The included cohort studies reported HMB in 25% (13/52) of women with Bernard-Soulier syndrome and in 22.1% (34/154) of women with Glanzmann thrombasthenia. In total, 164 deliveries in women with IPRD were described. Excessive bleeding occurred in 16.9% (11/65) of deliveries described in the largest cohort. PPH occurred in 63.2% (55/87) of deliveries described in case reports/series. PPH occurred in 73.7% (14/19) of deliveries that were not covered by prophylaxis compared with 54.2% (32/59) of deliveries that were (OR = 2.36, 95% CI 0.75-7.40). Neonatal bleeding complications were reported in 10.0% (8/80) of deliveries. In all (6/6) deliveries with neonatal bleeding complications wherein the presence of alloantibodies was investigated, either antiplatelet or anti-HLA antibodies were detected. DISCUSSION/CONCLUSION: Menstrual and particularly obstetrical bleeding problems frequently occur in women with IPRD, based on small case reports and series of poor quality. International collaboration, preferably on prospective studies, is needed to improve clinical management of women-specific bleeding in IPRD.

Gynaecological and obstetrical bleeding in women with factor XI deficiency - a systematic review.

INTRODUCTION: Menstrual bleeding, pregnancy and delivery present an intrinsic haemostatic challenge to women with bleeding disorders such as factor XI (FXI) deficiency. AIM: To provide a systematic overview of studies on gynaecological and obstetrical bleeding problems in women with FXI deficiency. METHODS: We searched MEDLINE, EMBASE and the Cochrane library for studies that present original data on the incidence of and treatment options for gynaecological and obstetrical bleeding in FXI-deficient women. RESULTS: We identified 27 studies, including a total of 372 women with FXI deficiency. All studies were observational, no interventional treatment studies were found. Most patients had a mild deficiency (FXI ≥ 20 IU dL-1 ). Heavy menstrual bleeding (HMB) was reported in 7-67%. In 7/19 (37%) women who underwent gynaecological procedures, a bleeding complication occurred, including in 2/7 hysterectomies (29%). About 3-20% of reported pregnancies ended in a miscarriage; of these miscarriages 0-25% (4/23 miscarriages) were complicated by bleeding. Terminations of pregnancies (TOP) were complicated by bleeding in 4 out of 11 cases (36%). In 90 out of 498 (18%) deliveries a postpartum haemorrhage (PPH) was reported, ranging from 0 to 50% in individual studies. In 21% (66/321) of deliveries, prophylaxis was given. This was associated with 9% (6/66) PPH, compared to 19% in deliveries without prophylaxis (84/432). Epidural analgesia was performed without complications in 44 patients. CONCLUSION: Women with FXI deficiency have a clearly increased risk of HMB, and of bleeding complications after miscarriage, TOP and delivery. No high quality data are available regarding prophylactic treatment.

Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies.

INTRODUCTION: A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. AIM: Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. METHODS: A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed. RESULTS: In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 µg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 µg kg(-1) (divided as three doses). CONCLUSION: Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies.

Gynaecological and obstetrical bleeding in Caucasian women with congenital factor XI deficiency: Results from a twenty-year, retrospective, observational study.

INTRODUCTION: Factor XI (FXI) deficiency is a mild bleeding disorder, common among Ashkenazis, that may be underestimated in Caucasians. Management of FXI deficiency in women is a challenge, due to its unpredictable bleeding tendency and the little evidence available on this issue. OBJECTIVE: To describe gynaecological/obstetrical bleeding complications and to analyze the effectiveness and safety of the antihaemorrhagic treatment among women with FXI deficiency. MATERIAL AND METHODS: A retrospective, observational study of 214 Caucasian subjects with FXI deficiency collected during 20 years (1994-2014) without clinical selection. RESULTS: We identified 95 women with FXI deficiency. Any haemorrhagic event was communicated by 26/95 (27.4%), being abnormal uterine bleeding the most frequently found (12/95, 12.6%). Nine postpartum haemorrhages were recorded from 136 deliveries (6.6%) in 57 women. Four postsurgical bleeding complications were registered among 25 gynaecological surgeries (16%) in 20 women. Abnormal uterine bleeding, postpartum and postsurgical haemorrhages were related to both a positive bleeding history and FXI:C values ≤43.5%. Prophylaxis with fresh frozen plasma, used in 12/25 (48%) gynaecological surgeries, did not prevent from postoperative bleeding in three cases, but two developed severe adverse reactions. CONCLUSION: Women with FXI deficiency, especially those with a positive history of bleeding or FXI:C ≤43.5%, are at risk of developing gynaecological/obstetrical haemorrhages, most of them mild/moderate. Systematic prophylaxis has questionable effectiveness, but might cause severe side effects.