Ligneous cervicitis and endometritis: A gynaecological presentation of congenital plasminogen deficiency.

BACKGROUND: Congenital plasminogen deficiency is a rare autosomal recessive condition. Plasminogen deficiency is thought to result in an inability of fibrin breakdown and therefore accumulation of fibrin and formation of ligneous changes. Ligneous lesions can form on a number of mucosal membranes including the cervix and endometrium. METHODS: We report the case of a 25-year-old woman with type 1 plasminogen deficiency with ligneous cervicitis and endometritis and her treatment and clinical course over the last few years. We then review the current literature of ligneous cases of the female genital tract and discuss available treatment options. KEY RESULTS: We found 30 reported cases of ligneous lesions affecting the female genital tract, with the cervix being the most affected part. A number of treatment options have been tried by our patient and other cases in the literature. These include use of the combined oral contraceptive pill, fresh frozen plasma infusion, topical plasmin and plasminogen and trial use of plasminogen concentrate. CONCLUSIONS: This is a chronic condition requiring a multidisciplinary approach. There is currently no definitive treatment for the condition, current trials with plasminogen concentrate replacement therapy may provide a promising option for these patients in the future.

Mode of delivery and cranial bleeding in newborns with haemophilia: a systematic review and meta-analysis of the literature.

OBJECTIVES: Cranial bleeding at birth can result in significant neurological morbidity in newborns with haemophilia. The optimum mode of delivery (MOD) of a potentially affected foetus remains controversial. AIM: The aim of this review is to ascertain overall incidence of cranial bleeding in newborns with haemophilia compared to the general population and the impact of MOD on rates of intracranial haemorrhage (ICH). METHOD: An EMBASE/MEDLINE search using key terms revealed the relevant studies. Studies included report the incidence of cranial bleeding by MOD within a newborn population. The heterogenicity across studies was assessed using Cochrane's Q test and I(2) statistic and studies were assigned appropriate weight based on a fixed-effect model. Odds ratio (OR) is the primary effect measure. RESULTS: Newborns with haemophilia are 44 times (95% CI: 34.7-57.1, P < 0.01) more likely to experience symptomatic ICH, and 8 times (95% CI: 5.38-12.6, P < 0.01) more likely to experience extracranial haemorrhage at birth, compared to the general population. In newborns with haemophilia the OR of experiencing ICH are 4.4 (95% CI: 1.46-13.7, P = 0.008) following an assisted vaginal delivery (AVD) and 0.34 (95% CI: 0.14-0.83, P = 0.018) following caesarean section (CS), compared to vaginal delivery. CONCLUSION: Cranial bleeding occurs with a significantly higher frequency in newborns with haemophilia compared to the general population. In newborns with haemophilia, delivery by a CS is associated with the lowest risk of ICH. AVD significantly increases the risk of ICH and should be avoided.

The role of rotational thromboelastometry in assessment of haemostasis during pregnancy in women with factor XI deficiency.

INTRODUCTION: Women with factor XI (FXI) deficiency are at an increased risk of bleeding complications at delivery. Obstetric management is complicated by a lack of correlation between FXI level and bleeding risk. AIM: The aims of this study were to assess the difference in rotational thromboelastometry (ROTEM® ) in parturient women with FXI deficiency compared to parturient and non-parturient controls and to evaluate the usefulness of ROTEM® in assessing bleeding risk at delivery in women with FXI deficiency. METHODS: ROTEM® was performed on 60 women: 27 with FXI deficiency, 20 age-matched parturient controls and 12 non-parturient controls. Pregnancy outcomes and haemostatic cover was reviewed in 57 deliveries of women with FXI deficiency. RESULTS: Women with FXI deficiency had a longer clotting time (CT) and clot formation time (CFT) (P < 0.001), reduced alpha angle (P < 0.001) but no difference in MCF (P = 0.054) compared to parturient controls. Compared to non-parturient controls, they had a longer CT (P < 0.001), but shorter CFT (P < 0.001), increased alpha angle (P < 0.001) and increased MCF (P = 0.005). ROTEM® was an additional helpful parameter in managing parturient women with FXI deficiency, reducing the need for factor administration. CONCLUSION: ROTEM® demonstrated hypercoagulable changes during pregnancy in women with FXI deficiency. However, they took longer to clot compared to parturient controls, but had increased clot consolidation and clot strength compared to non-parturient controls. ROTEM® is an additional test that is helpful to assess bleeding risk and provision of appropriate haemostatic cover at delivery.

Changes in factor XIII level during pregnancy.

Pregnancy is associated with significant haemostatic changes, with a progressive rise in most clotting factors. There is limited data on the changes of factor XIII (FXIII) level during pregnancy. This study assesses changes in FXIII activity during normal pregnancy and establish FXIII reference range during each trimester of pregnancy and immediate postnatal period. This is a cross sectional study of 376 women with normal uneventful pregnancies. Plasma FXIII activity was measured during first (weeks 0-12, n = 116), second (weeks 13-28, n = 132), third trimester (weeks 29-42, n = 128) and postnatal (day 0-3; n = 30). Samples were also collected from non-pregnant women (n = 25) as a control group. FXIII was assayed on CS-5100 analyser using chromogenic reagent. The mean ± SD FXIII activity was 112 ± 29 IU dL(-1) during first trimester, 96 ± 26 IU dL(-1) during second trimester, 83 ± 21 IU dL(-1) during third trimester, 90 ± 19 IU dL(-1) during postnatal period, and 113 ± 26 IU dL(-1) in the control. The reference range was calculated during the first (55-169 IU dL(-1)), second (45-147 IU dL(-1)), third trimester (42-125 IU dL(-1)) and postnatal period (61-137 IU dL(-1)). There was a significant reduction in the mean FXIII activity during the second and third trimester compared to the first trimester and control group (P < 0.0001). During the immediate postnatal period, the mean FXIII activity was not statistically different compared to the third and second trimester levels but was significantly lower compared to the first trimester (P < 0.0001) level and the control group (P = 0.0002). This study establishes the reference range for FXIII activity during the three trimesters of normal pregnancy and immediate postnatal period. Women have a significantly decreased level of FXIII activity during a normal uneventful pregnancy.

Congenital factor XIII deficiency in women: a systematic review of literature.

Factor XIII (FXIII) deficiency is a rare congenital bleeding disorder. There is a paucity of data in the literature about obstetrics and gynaecological problems in women affected by FXIII deficiency. The aim of this study was to examine gynaecological problems and obstetric complications and outcome in women with congenital FXIII deficiency. An electronic search was performed to identify the published literature on PUBMED, MEDLINE, EMBASE, Journals @OVID and CINAHL Plus databases using the following keywords: 'congenital factor XIII deficiency' AND 'women OR Pregnancy'. A total of 39 relevant articles were found and included in this systematic review; 27 case reports and 12 case series dating from 1964 to 2012. A total of 121 women were identified. Menorrhagia (26%) was the second most common bleeding reported after umbilical bleeding. Ovulation bleeding reported in 8% of women. Among 63 women, 192 pregnancies were reported; of these, 127 (66%) resulted in a miscarriage and 65 (34%) reached viability stage. In 136 pregnancies without prophylactic therapy, 124 (91%) resulted in a miscarriage and 12(9%) progressed to viability stage. Antepartum haemorrhage occurred in 5/65 (8%) pregnancies reaching viability stage while postpartum haemorrhage (PPH) seen in 16 (25%) cases. Women with congenital FXIII deficiency suffer significant bleeding complications. Menorrhagia and ovulation bleeding are common gynaecological problems and more prevalent than reported. Pregnancies in women with FXIII deficiency have a significant risk of miscarriage, placental abruption and PPH if not on prophylaxis treatment.

Pregnancy complications and obstetric care in women with inherited bleeding disorders.

Women with inherited bleeding disorders (IBD) require the input of a multidisciplinary team to improve outcomes of pregnancy. The role of the haemophilia nurse within the multidisciplinary team is to provide educational and emotional support to the women and to facilitate and co-ordinate patient-centred care. Prenatal diagnosis in cases of haemophilia is an integral part of the management of early pregnancy with a recent drive towards non-invasive prenatal diagnostic techniques. There is a current lack of data on the risk of miscarriage and bleeding complications during pregnancy. A clear association has only been established in women with fibrinogen and factor XIII deficiency. In the affected neonate with severe bleeding disorders such as haemophilia, the risk of head bleeding is significant, and appropriate management of labour and delivery has an important impact on reducing the risk. Women with IBD are at risk of both primary and secondary postpartum haemorrhage. Appropriate risk assessment and advance planning for haemostatic cover can reduce the bleeding risk.

The effect of labour on the coagulation system in the term neonate.

The coagulation system of the foetus is markedly different from that of adults. To assess the influence of maternal age, mode of delivery and intrapartum events, and foetal gender and weight on the foetal coagulation system. Cord blood was collected from 154 healthy pregnant women, with gestational age 37 - 42 weeks at birth. Mann-Whitney test was used for analysis of binary data and continuous variables were analysed using Pearson's correlation coefficient. Mean cord blood levels of FVIII:C, VWF:Ag, VWF:CB, FIX, FXI, FXII and plasminogen were significantly higher in babies delivered after labour, compared to those delivered after an elective caesarean. Mean cord blood levels of FII (P = 0.003), FV (P = 0.009), FVII (P = 0.0004) and FX (P = 0.0009) were significantly lower in the babies with meconium stained liquor in labour, compared with those with clear liquor. Augmentation with oxytocin, instrumental delivery, did not affect any of the factor levels and duration of labour did not have an effect on the level of coagulation proteins in cord blood. This study provides valuable information about effect of labour on the coagulation system of the foetus. It is concluded that, in cord blood, the results of coagulation parameters in the newborn baby should be considered in light of mode of delivery and events of labour.

The outcome of endometrial ablation in women with inherited bleeding disorders.

There are currently limited data on the use of endometrial ablation in the treatment of heavy menstrual bleeding (HMB) in women with inherited bleeding disorders (IBDs). A retrospective review of prospectively collected data was performed. Twelve women with IBDs who had received endometrial ablation for the treatment of HMB were identified and their records reviewed. Details of their menstrual history; quality of life (QOL) and amount of menstrual blood loss [as assessed by pictorial blood-loss assessment chart (PBAC) and haemoglobin (Hb) concentration] pre and post-ablation were collected. Twelve women were included. The median duration of follow-up post-ablation was 32 months (range, 6-76). The median duration of menstruation decreased from 11 to 0 days after treatment (P = 0.004). Median PBAC scores decreased from 1208 preop to 0 post-ablation (P = 0.002).The median Hb concentrations (10.5-13.1 g dL(-1)) and QOL scores (median, 17-54) improved significantly after endometrial ablation (P < 0.01). Endometrial ablation appears to be a safe and effective long-term treatment for HMB in women with IDBs. It significantly decreases menstrual blood loss and improves QOL.

A systematic review: The use of desmopressin for treatment and prophylaxis of bleeding disorders in pregnancy.

Desmopressin (DDAVP) is commonly used for treatment and prevention of bleeding complications in patients with bleeding disorders including haemophilia A, von Willebrand's disease (VWD) and other less common disorders. This article reviews the current evidence for the use of DDAVP in pregnancy to clarify its efficacy and safety with regard to maternal and foetal outcome. A search of the literature found 30 studies that reported DDAVP use in pregnancy for prophylaxis or treatment of bleeding complications with 216 pregnancies reported in total. The most common indication was prophylaxis for prevention of bleeding during pregnancy and postpartum haemorrhage. DDAVP was used successfully in the first and early second trimester for bleeding prophylaxis in 50 pregnancies. No postpartum bleeding complications were reported in 167 out of 172 pregnancies when DDAVP was used for peripartum haemostatic cover. Twenty-nine studies reported no significant adverse events as a result of treatment with DDAVP. One case of water intoxication seizure and one case of premature labour following the use of DDAVP was reported in a single study. Other maternal side effects included facial flushing and headache and were reported by one study. These side effects were generally well tolerated by patients. There were no other significant adverse events reported in any of the studies as a result of DDAVP use. Foetal outcome was recorded in ten studies with no adverse foetal outcomes. In conclusion, this review shows that DDAVP in selected cases is effective in reducing bleeding complications associated with pregnancy and childbirth with a good safety record. Further research is needed to confirm these findings as they are based on the currently available evidence from small studies and case series only.

Changes in the levels of factor VIII and von Willebrand factor in the puerperium.

To determine changes in Factor VIII (FVIII) and von Willebrand Factor (VWF) in the first 3 days of the puerperium. A prospective study assessing FVIII clotting activity, VWF activity and antigen levels in 95 women (with singleton uncomplicated pregnancies) during labour and on days 1, 2 and 3 of the puerperium. There were no significant differences in FVIII, VWF:Ag and VWF:CB on days 1 and 2 of the puerperium compared with levels during labour. There was a significant decrease in VWF:Ag (P = 0.009) and VWF:CB (P = 0.04) on day 3. Age, ethnicity, duration of labour and mode of delivery did not have any significant effect on the changes in FVIII and VWF levels. The pregnancy induced increase in FVIII and VWF is maintained in the first 48 h after delivery. VWF levels start to decline on day 3 postdelivery.

Management of pregnancy, labour and delivery in women with inherited bleeding disorders.

Pregnancy, labour and delivery present intrinsic haemostatic challenges to women with and carriers of bleeding disorders and their offspring. Deficiency of fibrinogen and factor XIII are associated with miscarriage, placental abruption and foetal loss. The risk of antenatal complications including antepartum haemorrhage is unknown in women with other bleeding disorders. There is a significant risk of postpartum haemorrhage (primary and secondary) in women with all types of bleeding disorders. This can be serious and life threatening in those with severe defects such as Bernard Soulier syndrome and Glanzmann's thrombasthenia. Three to four percent of infants with haemophilia experience cranial bleeding that occurs during labour and delivery. The safest method of delivery for affected babies remains controversial. However, the rate of planned Caesarean section is increasing among known carriers of haemophilia. If vaginal delivery is planned, prolonged labour and difficult delivery especially vacuum extraction are associated with the highest risk of cranial bleeding and should be avoided. The optimal management of pregnancy in women with inherited bleeding disorders requires a multidisciplinary approach and advanced individualized management plan taking into consideration obstetric and bleeding risk factors. Women with mild or moderate bleeding disorders can be managed at their local maternity unit in close collaboration with a tertiary centre. However, those with severe or rare disorders or carrying an affected infant should be managed in a tertiary centre with an onsite Haemophilia centre.

Seroprevalence and risk factors of toxoplasmosis among University of Kirkuk female students.

The study was conducted in the College of Education/Hawija, University of Kirkuk from September 1st, 2018 until the period February 28th, 2019. The first part included determine the prevalence of Toxoplasma gondii, which involved collecting blood from the female students from different stages in the different colleges of the University of Kirkuk, Kirkuk province (northeastern Iraq), ranged ˂20-24 years old. All necessary information was recorded using a questionnaire prepared for this purpose. In the current cross-sectional study, 210 blood specimens were collected from participants. Blood specimens were examined for evaluated the levels of specific anti-toxoplasma IgM and IgG antibodies using the protocol of an enzyme-linked immunosorbent assay (ELISA). The results revealed that the total infection of Toxoplasma gondii antibodies was 9.05% for IgG via 3.33% for IgM with significant difference at p<0.05. According to risk factors, the univariate logistic regression analysis revealed that only increase in domestic cats' owners and directly contact with the soil (gardening in the house) had a corresponding increase with distribution of the infection (p<0.05). Data in the present study revealed that the toxoplasmosis seroprevalence ratio among participants was 12.38%. It was observed that all of the risk factors in the present study had no statistically association with the toxoplasmosis seroprevalence, except cat ownership and house gardening once, where they were showed a highest odd ratio.

Laparoscopic management of a full-thickness uterine niche with subsequent pregnancy outcome.

BACKGROUND: Uterine niche is the consequence of impaired healing of the myometrium following a lower segment transverse caesarean section (CS). Although there is conflicting evidence on the management of these cases, laparoscopic repair is a commonly used surgical treatment modality. OBJECTIVES: To demonstrate the management and laparoscopic repair of the niche with subsequent pregnancy outcome. MATERIALS AND METHODS: We report a case of a 33-year-old patient who had a significant haematoma in the niche. The haematoma resolved after conservative management however, she remained symptomatic. Therefore, she had a laparoscopic repair. The narrated surgical video article demonstrates the dissection of the uterovesical fold overlying the niche, followed by the excision of the scar tissue and its repair with laparoscopic suturing. Ultrasound and magnetic resonance imaging images of the uterus demonstrating the haematoma at the caesarean section site, the niche after resolution of the haematoma and post-repair imaging are also provided. MAIN OUTCOME MEASURES: Repair of the niche, symptomatic relief of abnormal uterine bleeding, spontaneous conception and live birth. Ultrasonographic images also demonstrate uterine wall continuity post laparoscopic repair. RESULTS: The patient recovered uneventfully. Full-thickness of myometrium was demonstrated with post-operative imaging and confirmed at the subsequent caesarean section. Gynaecological symptoms resolved following the repair. The patient conceived spontaneously after surgery and delivered at term by caesarean section without any complications. CONCLUSION: Laparoscopic management of the niche should be considered where there is a complete myometrial defect or significant thinning of the myometrium, especially in symptomatic women who desire future pregnancy.

The impact of menstrual disorders on quality of life in women with inherited bleeding disorders.

SUMMARY: Menorrhagia, heavy menstrual bleeding, is a common condition that has a substantial impact on the lives of many women. The objective measurement of menorrhagia is often impractical; therefore diagnosis and treatment are usually based on the direct perception of the woman. Menstrual problems are likely to be worse in women with bleeding disorders, as they are more likely to have heavy and painful menstrual periods and ovulation bleeding and pain. These can have a major impact on the quality of women's lives, especially those who suffer heavy menstruation. These problems can also lead to limitations at work and school and hinder educational and academic achievements. Only few studies describe how quality of life (QOL) changes in women with an underlying haemostatic defect; poorer QOL being associated with more frequent bleeding symptoms. Early recognition, accurate diagnosis and appropriate management of bleeding disorders should improve not only the quality of care for affected women but also their QOL. Increased awareness of the high prevalence of menstrual problems especially menorrhagia is essential for early diagnosis and provision of appropriate treatments without any delay. Accurate knowledge of the impact of menorrhagia on health-related quality of life (HRQOL) and its adequate assessment help individualize treatment and assess the magnitude of changes in HRQOL. An ideal situation would be to use a generic and a disease-specific measure together so that comparisons can be made on a general and disease-specific level.

Bernard Soulier syndrome in pregnancy: a systematic review.

Bernard Soulier syndrome (BSS) is a rare disorder of platelets, inherited mainly as an autosomal recessive trait. It is characterised by qualitative and quantitative defects of the platelet membrane glycoprotein (GP) Ib-IX-V complex. The main clinical characteristics are thrombocytopenia, prolonged bleeding time and the presence of giant platelets. Data on the clinical course and outcome of pregnancy in women with Bernard Soulier syndrome is scattered in individual case reports. In this paper, we performed a systematic review of literature and identified 16 relevant articles; all case reports that included 30 pregnancies among 18 women. Primary postpartum haemorrhage was reported in 10 (33%) and secondary in 12 (40%) of pregnancies, requiring blood transfusion in 15 pregnancies. Two women had an emergency obstetric hysterectomy. Alloimmune thrombocytopenia was reported in 6 neonates, with one intrauterine death and one neonatal death. Bernard Soulier syndrome in pregnancy is associated with a high risk of serious bleeding for the mother and the neonate. A multidisciplinary team approach and individualised management plan for such women are required to minimise these risks. An international registry is recommended to obtain further knowledge in managing women with this rare disorder.

The effect of fetal sex on the outcome of labour induction.

The aim of this study was to determine the effect of fetal sex on the process and the outcome of induction of labour. This was a retrospective study of 658 women carrying singleton cephalic pregnancies induced at 37-42 completed weeks' gestation. Male fetuses demonstrated significantly more CTG abnormalities and need for fetal blood sampling. Male infants were also more likely to be delivered by emergency caesarean section. The total admission rate to the neonatal unit was higher among male babies. Male infants do not tolerate induction of labour as well as females. Fetal sex can be used as a predictive factor of the outcome in cases of induced labour.

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

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.

Relevance of quantitative assessment of bleeding in haemorrhagic disorders.

In the last few years, there has been a growing interest in the diagnosis of mild bleeding disorders (MBD) to find reliable tools for the assessment of their inherent bleeding risk and minimum criteria for the definition of a clinically useful diagnosis. Unlike in more severe haemorrhagic disorders, in MBD, the bleeding history may overlap with that reported by normal people. This problem has required the development of strategies that could allow the assessment of bleeding symptoms from both a qualitative (presence or absence) and quantitative (bleeding severity) aspect. An example of high quality clinical research in bleeding disorders was given by the systematic approach used for the evaluation of menorrhagia. For this symptom, the most common in women with bleeding disorders, the use of pictorial charts provided many new insights. Dr Kadir will review its use in a clinical context. The assessment of the whole bleeding history requires first, the development of reproducible tools to collect symptoms and secondly, formulation of easily applicable criteria to convert the collected data into clinical information. Dr Tosetto will propose a bleeding questionnaire in which clinical criteria were developed and validated, and show how a summative, quantitative index of bleeding severity (the Bleeding Score) could be used in von Willebrand disease. Finally, Dr James will review the development of quantitative analysis in children, a particularly important and difficult application, but one that needs to be tackled urgently.

Pregnancy in carriers of haemophilia.

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.