Recent advances in prenatal diagnosis and multidisciplinary management has improved the reproductive outlook for carriers of hemophilia and their offspring. Pre-pregnancy planning allows the woman and her partner to explore reproductive options and prepares the family for the potential delivery of an affected male infant. Non-invasive methods of prenatal diagnosis are advancing, with the aim of providing a definitive test for hemophilia. Carriers of hemophilia have an increased risk of primary and secondary postpartum hemorrhage. The affected male offspring is potentially at risk of cranial bleeding during delivery. A multidisciplinary approach provides advanced planning for the optimum mode of delivery and provision of appropriate haemostatic cover to reduce the risk of bleeding complications. This review summarises current recommendations for pregnancy management in carriers of hemophilia, from the initial pre-pregnancy counseling through to delivery and care of the neonate.

Background Thrombin activatable fibrinolysis (TAFI) is a glycoprotein that inhibits fibrinolysis. Pro-TAFI is cleaved by Factor IIa – Thrombomodulin complex, producing actived TAFI (TAFI:Ac). Pregnancy is a hypercoaguable state associated with increased levels of pro-coagulant factors; enhanced thrombin generation and impaired fibrinolysis. TAFI may contribute to the decreased fibrinolysis seen in pregnancy. Currently there are conflicting reports on TAFI antigen (TAFI:Ag) levels in pregnancy and no data on the dynamic changes in levels and activity during pregnancy and its correlation with adverse pregnancy outcome. Method Consecutive TAFI:Ag and activity (TAFI:Ac) levels were measured during the first, second and third trimester in 80 women. All participants in the study had no co-morbidities and had an uncomplicated singleton pregnancy. Results TAFI:Ag levels significantly increased with gestation peaking in the third trimester with mean levels of 120, 139 and 148 μg/ml in the first, second and third trimesters respectively (p<0.035). TAFI:Ac levels significantly increased between the first and second trimesters with mean values of 47 and 52 μg/ml respectively (p<0.01). TAFI:Ac levels then plateaued in the third trimester (with a mean value of 53 μg/ml). Conclusion TAFI antigen and activity levels are increased in normal pregnancy

Rare bleeding disorders include deficiency of fibrinogen, prothrombin, factor V, factor VII, factor X, factor XI and factor XIII together with combined deficiency disorders, factor V+VIII deficiency, and deficiency of the vitamin K-dependent factors (factor II, VII, IX and X). They account for 3-5% of all inherited coagulation disorders. Due to their rarity, information about pregnancy complications and management is limited and mostly derived from case reports. Deficiency of fibrinogen and FXIII are both found to be strongly associated with increased risk of recurrent miscarriage and placental abruption. Factor replacement is used to reduce these risks. However, the risk of miscarriage and antepartum complications is less clear in women with other bleeding disorders. Haemostatic abnormalities in women with rare bleeding disorders seem to persist throughout pregnancy especially if the defect is severe. Therefore women affected with these disorders are at risk of post-partum haemorrhage. The fetus can also be affected and potentially at risk of bleeding complications. Specialised multidisciplinary management is essential to minimise the potential maternal and neonatal complications and ensure an optimal outcome. This paper presents literature review for pregnancy complications in each of the rare bleeding disorders. In addition general principles for management of pregnancy, labour and delivery are discussed.

Bennich G, Langhoff-Roos J. 2005. Placenta percreta treated using a new surgical technique. European Journal of Obstetrics, Gynecology and Reproductive Biology 122:122–125. Chou MM, Ho ES, Lee YH. 2000. Prenatal diagnosis of placenta previa and accrete by transabdominal color Doppler ultrasound. Ultrasound in Obstetrics and Gynecology 15:28–35. Gilliam M, Rosenberg D, Davis F. 2002. The likelihood of placenta previa with greater number of caesarean deliveries and higher parity. Journal of Obstetrics and Gynecology 99:976– 980. Morkon NH, Henriksen H. 2001. Placenta percreta – two cases and review of the literature. European Journal of Obstetrics and Gynecology 100:112–115. Morrison JE. 1978. Placenta accreta. A clinicopathologic review of 67 cases. Journal of Obstetrics and Gynecology 7:107–123. Wong HS, Parker S. 2005. Ultrasound findings in conservatively treated placenta percreta. Ultrasound in Obstetrics and Gynecology 26:580–582.

The objectives of this study were to identify the impact of menorrhagia on the health-related quality of life (HRQOL) of women in general and those with inherited bleeding disorders and to identify the commonly used tools in assessing quality of life. A review of studies evaluating quality of life in women suffering from menorrhagia was conducted. Data sources used included electronic databases Medline and Embase. Reference lists and bibliographies of the relevant papers and books were hand-searched for additional studies. Eighteen of the 53 studies identified measured quality of life prior to treatment of menorrhagia. Ten of the studies used a validated measure of quality of life. Five studies involving a total of 1171 women with menorrhagia in general and using SF-36 were considered for further review. The mean SF-36 scores in women with menorrhagia were worse in all the eight scales when compared with normative scores from a general population of women. Three studies, involving 187 women, assessed the quality of life in women with menorrhagia and inherited bleeding disorders. None of these studies used a validated HRQOL score making it difficult for comparison. However, all reported poorer scores in study women compared to the controls. In conclusion, HRQOL is adversely affected in women with menorrhagia in general and in those with inherited bleeding disorders. HRQOL evaluation is useful in the management of women with menorrhagia for assessment of treatment efficacy.

Background: There are currently limited data on the use of the levonorgestrel-releasing intrauterine system (LNG-IUS) for the management of heavy menstrual bleeding (HMB) in women with inherited bleeding disorders (IBDs) particularly on its long-term (>12 months) efficacy. Study Design: This study involves a case series of women with IBDs who received the LNG-IUS as treatment for HMB. Menstrual blood loss before its insertion and at the time of follow-up was assessed by the pictorial blood-loss assessment chart (PBAC) and hemoglobin (Hb) concentrations. A questionnaire was used to evaluate quality of life (QOL) during menstruation before and after insertion of the LNG-IUS. Results: Twenty-six women were included. The median duration of LNG-IUS use at follow-up was 33 months (range, 14-103). The median PBAC score decreased from 255 (range, 134-683) to 35 (range, 0-89) with LNG-IUS use. The median Hb concentrations (11.2 to 13.2 g/dL) and QOL scores (median, 26 to 52) improved significantly with LNG-IUS use (p<.01). Conclusion: The LNG-IUS appears to be an effective long-term treatment for HMB in women with IBDs. (C) 2011 Elsevier Inc. All rights reserved.

The aim of the study was to review the complications, management and outcome of pregnancy in carriers of haemophilia over a 10-year period following the introduction of a multidisciplinary management guideline. Comparison was made to a 10-year cohort prior to implementation of the guidelines. A retrospective review of case notes of carriers of haemophilia (41 haemophilia A, 12 haemophilia B) who had received obstetric care at the Royal Free Hospital between 1995 and 2005 was conducted. There were 90 pregnancies (65 live births, 13 miscarriages, 12 terminations). Prenatal testing was taken up in 97% (63/65) of pregnancies where the mother was known to be a carrier of haemophilia. The majority (71%; 46/65) chose only to have non-invasive fetal sex determination. Seventeen (26%) had invasive testing (13 primarily for haemophilia and four primarily for chromosomal abnormalities). Termination of pregnancy was opted for in 67% (6/9) of pregnancies affected with haemophilia. Pregnancy was accompanied by a marked rise in factor VIII levels compared to only a small rise in factor IX levels. Invasive intrapartum monitoring techniques and instrumental deliveries were avoided in all pregnancies known to be at risk of haemophilia. Regional block was performed in 25 pregnancies for labour/delivery with no complications. The caesarean section rate was 47%. The incidence of primary and secondary postpartum haemorrhage was 19% and 2%, respectively. There were two neonatal head bleeding complications associated with prolonged labour or instrumental delivery. Availability of management guideline and care provided in a multidisciplinary approach can help to minimize bleeding complications in carriers of haemophilia and their newborns.

A study was conducted to evaluate the value of screening for inherited bleeding disorders in women with primary postpartum haemorrhage (PPH). Over a 2-year period, women identified to have PPH (defined as > 500 mL blood loss for spontaneous vaginal delivery, > 700 mL for instrumental deliveries and > 1000 mL for caesarean sections within 24 h of delivery) were invited to participate in this study testing for a possible underlying bleeding disorder at 3-9 months postdelivery. Women known to have an inherited bleeding disorder were excluded. Of the 5744 deliveries in our unit during the study period, 152 (3%) fulfilled the criteria for primary PPH and 50 women agreed to participate in the study. Of these, 25 (50%) had a spontaneous vaginal delivery, 8 (16%) had an instrumental delivery and 17 (34%) had a caesarean section. Half of the women were multiparous and five (20%) had PPH in their previous pregnancy. Nineteen (38%) and 12 (24%) reported at least one significant personal and family bleeding history, respectively. One (2%) woman was identified to have von Willebrand disease. In conclusion, primary PPH does not appear to be a strong predictor of inherited bleeding disorders. Further studies are required to assess the prevalence of inherited bleeding disorders among these women.

Women face particular hemostatic challenges during their life owing to their monthly menstruation and childbirth. Thus women with inherited bleeding disorders are particularly at risk. Hemophilia, a severe bleeding disorder characterized by recurrent, potentially life-threatening bleeding episodes, is commonly considered as a condition associated with men due to its X-linked inheritance. Its incidence is approximately one in 10,000 male births. It became a widely recognized disorder as a result of its existence in the royal family. Queen Victoria was identified to be a carrier of hemophilia soon after the birth of her eighth child, Leopold, who had inherited the disorder. Although hemophilia affects men, women who are carriers may also have low clotting factor levels and hence experience considerable bleeding problems. More importantly, von Willebrand's disease (VWD), the most common bleeding disorder, with an incidence of 1% (1) in the general population, presents more commonly in women despite affecting both men and women. In the original description by Eric von Willebrand (2), 16 of the 23 affected members of the extended family were females, including the index case, who ultimately bled to death at the onset of her fourth menstrual period at age 13 years. Although her mother safely delivered 12 children, her grandmother died in childbirth due to postpartum hemorrhage (PPH). A significant proportion of women presenting with menorrhagia have an underlying inherited bleeding disorder (4). A systematic review of 11 prevalence studies of VWD in 988 women with menorrhagia has reported an overall prevalence of 13% (3). Conversely, menorrhagia is one of the commonest symptoms in women with inherited bleeding disorders. In published series, 32–100% of women with type 1 VWD and 10–70% of those with other inherited bleeding disorders were reported to have heavy menstrual periods (5). Using a semi-objective method, the pictorial blood assessment chart (PBAC) to assess menstrual loss, menorrhagia was found in 74%, 59%, and 57% of women with VWD, factor XI deficiency, and VWD respectively (6). The duration of menstruation was also found to be significantly longer and episodes of flooding more common in women with inherited bleeding disorders (p = 0.001). A significant proportion of women with VWD have undergone hysterectomy for menorrhagia and often at a young age, as early as 14 years old (7). The health status and health-related quality of life (HRQL) of individuals with VWD is significantly worse in females compared to males (8). The overall HRQL scores amongst these women have been found to be as low as those in HIV-infected individuals with severe hemophilia. Women with VWD are less likely to achieve postsecondary education (5.5% of females compared to 35% males) (8). This could be explained by the frequent absenteeism from school due to menstrual problems. Menstruation has been shown to have a significant impact on the quality of life of women with VWD: 39% had to cut down the time they spent on work and other activities; 47% felt they had accomplished less than they would like; and 38% were limited by the type of work they could do (9). Childbirth presents another hemostatic challenge to women with inherited bleeding disorders. Amongst hemophilia carriers, the incidence of primary and secondary PPH has been reported to be 22% and 11% compared to 5% and 0.7%, respectively, in the general population (10). In three series, which included 51 women with VWD and information on 92 deliveries, primary and secondary PPH complicated 16–29% and 20–29% of pregnancies, respectively (11–13). There is undoubtedly a lack of awareness of the significant obstetric and gynecological morbidities of inherited bleeding disorders. In a recent survey amongst obstetricians and gynecologists in the UK, more than 80% of the respondents considered the prevalence of VWD in women with menorrhagia and no gynecological pathology to be less than 1% while the reported prevalence in the literature is 13% (14). Consequently, only 12% and 2% of the respondents would consider testing for VWD in an 18- and a 35 year-old with such a presentation. This is comparable to the findings of a survey from the USA where 16% and 4% of gynecologists were likely to consider VWD as the cause of menorrhagia in girls near menarche and in women of reproductive age, respectively (15). There is currently an international effort via organizations such as the Haemophilia Society (Women Bleed Too) in the UK and National Hemophilia Foundation (Project Red Flag) in the USA to address and raise the awareness of these issues in order to identify and improve the quality of care and life of women with inherited bleeding disorders. Guidelines on the obstetric and gynecological management of these women were published recently in support of these initiatives (16). In this era when, as a result of the reduced size of families, women experience a significantly higher number of menstrual periods in their lifetime compared to their ancestors, it is important for health care providers to recognize the significant adverse effects of inherited bleeding disorders on women and that not only men can be affected by severe bleeding disorders, as ‘women bleed too’.

Ten carriers of haemophilia referred for prenatal diagnosis were offered first trimester non‐invasive fetal gender determination by ultrasound and analysis of free fetal DNA (ffDNA) in maternal plasma in an attempt to reduce the need for an invasive diagnostic procedure in female pregnancies. Although repeat testing was required in three cases, fetal gender was determined correctly in all cases (four females, six males) at a median gestation of 12 +3 (11 +2 to 14 +1 ) using both methods. In all cases of a female fetus, the mothers opted not to have invasive testing. Both methods provide a reliable option of avoiding invasive testing in female pregnancies.

A pilot study was conducted over a 6-month period to evaluate antenatal screening for factor XI (FXI) deficiency amongst Ashkenazi Jewish women booking for their pregnancy in a single obstetric unit. Fifty-four women of Ashkenazi Jewish origin were recruited during their visit for the routine first trimester ultrasound scan. They completed a questionnaire about their personal bleeding symptoms and had blood taken for FXI levels (FXI:C). Seven (13%) women had partial FXI deficiency. Five (9%) were newly diagnosed, and in the remaining two, the diagnosis was known previously. One infant with severe FXI deficiency was identified as a result of maternal testing. This study has shown that FXI deficiency is common amongst women of Ashkenazi Jewish origin and supports its antenatal screening in this population. However, further studies are required to evaluate its cost-effectiveness and the effect on pregnancy outcome.

The gynaecological and obstetric management of women with inherited coagulation disorders requires close collaboration between obstetrician/gynaecologists and haematologists. Ideally these women should be managed in a joint disciplinary clinic where expertise and facilities are available to provide comprehensive assessment of the bleeding disorder and a combined plan of management. The haematologist should arrange and interpret laboratory tests and make provision for appropriate replacement therapy. These guidelines have been provided for healthcare professionals for information and guidance and it is also intended that they are readily available for women with bleeding disorders.

A mail survey of members and fellows of Royal College of Obstetricians and Gynaecologists was carried out to determine current practices of obstetricians and gynaecologists in the United Kingdom in the management of women with inherited bleeding disorders. In total, 3929 questionnaires were sent, 707 returned and analysis was limited to 545 valid questionnaires. In the past 5 years, 91% have managed women with inherited bleeding disorders. The majority (83%) considered inherited bleeding disorders to be under diagnosed in obstetrics and gynaecology. More than 80% considered the prevalence of von Willebrand's disease (VWD) to be < 0.2% in the general population and < 1% in women with menorrhagia and no gynaecological pathology, although the reported prevalence is 1% and 5-25% respectively. Twelve percent of the respondents would arrange testing for VWD when reviewing an 18-year-old with menorrhagia and no pelvic pathology, while only 2% would do the same for a 35-year-old with the same presentation. Twenty-one percent thought elective caesarean section is indicated in all fetuses known to be at risk of being affected by haemophilia. Eighty-four percent considered vacuum extraction unsafe in these cases, but 76% would consider the use of low forceps. In conclusion, obstetricians and gynaecologists underestimate inherited bleeding disorders as an underlying cause for menorrhagia. Increased awareness and management guidelines are essential in minimizing haemorrhagic complications and improving quality of care of these women.

A 30-year-old waitress booked at 15 weeks in her second pregnancy. At her booking visit she gave a history of a painless swelling in her left groin. On examination she had a 10-cm lump in her left groin. The swelling was reducible, soft and non-tender. On further questioning she gave a history of the same swelling in her left groin in her first pregnancy that resolved spontaneously after delivery. A provisional diagnosis of a left inguinal hernia was made. She was referred to the general surgeons for advice on subsequent management. On review at 28 weeks' gestation she was well but the groin swelling had persisted (see Fig. 1) and was no longer reducible. There were no signs of obstruction. The general surgeons recommended conservative management with a plan to discuss surgical repair postnatally. She also reported unsightly varicose veins on her left leg and an occasional ache from the groin swelling. Left inguinal swelling caused by round ligament varicosities. An ultrasound of the lump was arranged and revealed multiple dilated varicosities within and around the round ligament extending from the left inguinal ring, through the inguinal canal. No loops of bowel were present and there was no evidence of a varix thrombus. She went into spontaneous labor at term followed by an uncomplicated vaginal delivery. She was reviewed at 6 weeks' postdelivery and on examination the inguinal swelling was no longer present. There are several differential diagnoses for a groin swelling. The most common of which, is an inguinal hernia, although it occurs 10 times less frequently in women than in men. Its incidence in pregnancy has been reported as 1 in 1000–3000 (1). Other causes of a groin swelling include a femoral hernia, an enlarged lymph node, a vascular aneurysm and a subcutaneous lipoma. In women, persistent embryonic remnants of the process vaginalis can enlarge to form cysts and by traversing the inguinal canal may produce a bulge in the anterior part of the labium majora. Less commonly round ligament varicosities may also present as an inguinal mass (2). We report a case of round ligament varicosities mimicking an inguinal hernia in pregnancy. The distinction between the two is difficult clinically as the symptoms and signs are similar. Both traverse the inguinal canal. Both can be reducible or irreducible, as round ligament varicosities are valveless and may not empty completely. Round ligament varicosities also transmit cough impulses, similar to inguinal hernias, because transmitted abdominal pressure leads to vein distension. A clue that may suggest round ligament varicosities is the coexistence of lower limb or labial varicosities. The incidence of round ligament varicosities is unknown, but physiological changes in pregnancy can precipitate their formation. These include relaxation of venous smooth muscle, an increase in venous return from the lower limbs and pelvic venous obstruction caused by the gravid uterus. Ultrasound examination has been reported as a useful diagnostic tool in distinguishing round ligament varicosities from an inguinal hernia (2). The characteristic ultrasound appearances of varicosities simulating pelvic masses in pregnant and non-pregnant women have been described using high-resolution real time ultrasonic equipment (3). These include a prominent venous plexus with accompanying dilated draining veins and the typical 'bag of worms' appearances of smaller varices. Round ligament varicosities require close monitoring during pregnancy as rupture of varices and acute variceal thrombosis, especially in the peripartum period, have both been reported (4,5). Painful groin swellings need prompt investigation, and surgical exploration may be required. This case highlights the potential difficulty in diagnosing inguinal swellings clinically in pregnancy. By increasing the awareness of round ligament varicosities as part of the differential diagnosis and by highlighting the importance of ultrasound examination, we hope unnecessary surgery and its associated morbidity can be avoided.