Claudia Chi

The obstetric and gynaecological management of women with inherited bleeding disorders – review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors’ Organization

Summary.  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.

Pregnancy and rare bleeding disorders

Summary.  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 ante‐partum 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.

Pregnancy in carriers of haemophilia

Summary.  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.

Review of quality of life: menorrhagia in women with or without inherited bleeding disorders

Summary.  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.

Menorrhagia in Adolescents with Inherited Bleeding Disorders

STUDY OBJECTIVES We reviewed the management and treatment outcomes of menorrhagia in adolescents with inherited bleeding disorders and assessed the impact of menorrhagia on their quality of life. DESIGN Retrospective review of case notes and a questionnaire study. SETTING Comprehensive-care hemophilia treatment center. PARTICIPANTS Adolescents with inherited bleeding disorders who had registered at the center and were attending the multidisciplinary hemophilia and gynecology clinic for management of menorrhagia. INTERVENTIONS Review of medical records and assessment of menstrual blood loss using the pictorial blood assessment chart and quality of life measurements during menstruation using a questionnaire. MAIN OUTCOME MEASURES Scores on pictorial blood assessment charts and quality of life measurements before and after treatment. RESULTS Of 153 girls aged 12 to 19 years who had registered at the center and had an inherited bleeding disorder, 42 (27%) attended the multidisciplinary clinic for management of menorrhagia. The majority (38/42; 90%) had experienced menorrhagia since menarche. Of the group, 5 (12%) required hospital admission for acute menorrhagia and severe anemia. Treatment options for menorrhagia included tranexamic acid, desmopressin, combined oral contraceptive pills, clotting factor concentrate, and the levonorgestrel intrauterine system. These treatment modalities, alone or in combination, were associated with a reduction in menstrual blood loss (median pre- and posttreatment pictorial blood assessment chart scores were 215 and 88, respectively) and improvement in quality of life scores (median pre- and posttreatment were 26 and 44, respectively). CONCLUSIONS Menorrhagia is a common symptom in adolescents with inherited bleeding disorders. It can present acutely, and it adversely affects quality of life. Treatment options include hemostatic and/or hormonal therapies and can improve the quality of life of affected girls.

Levonorgestrel-releasing intrauterine system for the management of heavy menstrual bleeding in women with inherited bleeding disorders: long-term follow-up.

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.

Non‐invasive first trimester determination of fetal gender: a new approach for prenatal diagnosis of haemophilia

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.

Identification and management of women with inherited bleeding disorders: a survey of obstetricians and gynaecologists in the United Kingdom

Summary.  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 Willebrands 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.

The obstetric experience of women with factor XI deficiency

Objectives. To assess the obstetric outcome in women with factor XI (FXI) deficiency. Design. Retrospective review of medical records. Setting. Tertiary referral university hospital. Population. Women with FXI deficiency. Method. Review of pregnancies over a 10‐year period (1997–2006). Main outcome measures. Pregnancy outcome, mode of delivery, changes in FXI levels during pregnancy, use of prophylaxis during labor and delivery, antepartum hemorrhage, and postpartum hemorrhage (PPH). Results. There were 61 pregnancies among 30 women with FXI deficiency (two severe, FXI level <15–20 IU/dL, and 28 partial, FXI level 20–70 IU/dL) resulting in 49 live births (two sets of twins), eight miscarriages, and six terminations of pregnancy. The modes of delivery included 38 spontaneous vaginal deliveries, three instrumental deliveries, and six cesarean sections (two emergency and four elective). No significant change in FXI levels was observed during pregnancy. Intrapartum prophylaxis with FXI concentrate or tranexamic acid was given in 19 deliveries where the mother had a positive bleeding history. Four women had excessive bleeding related to pregnancy loss and three experienced antepartum bleeding. All these women had a positive bleeding history. There were five (11%) primary and five (11%) secondary PPHs among seven women including four with a positive bleeding history. Conclusion. Women with FXI deficiency, particularly those with a positive bleeding history, are at risk of bleeding complications related to miscarriage or childbirth. The unpredictable nature of their bleeding tendency demands careful planning and close collaborations between obstetricians and hematologists.

Inherited bleeding disorders in pregnancy

Women with inherited bleeding disorders may face several haemostatic challenges during pregnancy and childbirth. Pregnancy in these women requires specialised and individualised care. Prenatal diagnosis is primarily considered in families affected by severe bleeding disorder such as haemophilia. Non-invasive fetal sex determination by analysis of free fetal DNA in maternal blood offers carriers of haemophilia a means of avoiding invasive testing and its associated risks in female pregnancies. With the exception of fibrinogen and factor XIII deficiencies, it is currently unclear whether women with inherited bleeding disorders are at increased risk of miscarriage or antepartum haemorrhage. However, they are at increased risk of primary and secondary postpartum haemorrhage. The fetus, if severely affected, is at risk of cranial bleeding during labour and delivery. Appropriate haemostatic cover during labour and delivery, avoidance of prolonged labour and traumatic delivery, and active management of third stage of labour can minimise the risk of bleeding complications for the mother and her fetus.