Pictorial Bleeding Assessment Chart Scores Research Articles

Comparison of Bleeding Pattern and Quality of Life Before and After the Insertion of a Levonorgestrel Intrauterine System for Heavy Menstrual Bleeding: A Seven-Year Review.

Background This study aimed to examine the role of a levonorgestrel intrauterine system (LNG-IUS) in the treatment of heavy menstrual bleeding (HMB) regarding improvements in bleeding patterns and quality of life (QOL) and determine the reason for its failure or withdrawal from treatment in some patients. Methodology This retrospective study was conducted in a tertiary care center in eastern India. A seven-year assessment, with both qualitative and quantitative assessments, of the effect of LNG-IUS in women with HMB was performed using the Menorrhagia Multiattribute Scale (MMAS) and Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) score as a tool to assess the QOL, and the pictorial bleeding assessment chart (PBAC) to assess bleeding patterns. The study population was divided into the following four groups based on duration: three months to one year, one to two years, two to three years, and more than years.The continuation, expulsion, and hysterectomy rates were evaluated. Results The mean MMAS and MOS SF-36 scores increased significantly (p < 0.05) from 36.73 ± 20.40 to 93.72 ± 14.62 and 35.33 ± 6.73 to 90.54 ± 15.89, respectively. The mean PBAC score decreased from 176.36 ± 79.85 to 32.19 ± 63.87. In total, 348 women (94.25%) continued the LNG-IUS, and 3.44% had uncontrolled menorrhagia. Furthermore, at the end of seven years, the expulsion rate was 2.28% due to adenomyosis and pelvic inflammatory disease, and the hysterectomy rate was 5.75%. In addition, 45.97% and 48.27% of the participants had amenorrhea and hypomenorrhea, respectively. Conclusions LNG-IUS improves bleeding and QOL in women with HMB. In addition, it requires less skill and is a non-invasive and nonsurgical option, which should be considered first.

Reduced Activity and Quality of Life in Women Soldiers with Heavy Menstrual Bleeding and Dysmenorrhea.

The aim of the study was to examine the effect of heavy menstrual bleeding (HMB) and dysmenorrhea on daily activity and quality of life (QoL) in young women engaged in demanding activities. Cross-sectional study. A total of 422 Israeli women soldiers in combat and non-combat roles. Participants were asked to provide consent and to complete study questionnaires. A pictorial bleeding assessment chart (PBAC), visual analog scale (VAS), verbal multidimensional scoring system for assessment of dysmenorrhea, and approved Hebrew-translated age-appropriate Pediatric Quality of Life Inventory (PedsQL). HMB (PBAC >100) and severe HMB (PBAC >185) were demonstrated in 181 (50%) and 96 (26%) participants, respectively. A high PBAC score was recorded in 20% who answered "no" or "unknown" in the questionnaire on having HMB. Mild, moderate, and severe dysmenorrhea were demonstrated in 80 (21.5%), 115 (31%), and 142 (38%) participants, respectively. The prevalence of HMB and dysmenorrhea was similar in soldiers in combat and non-combat roles. Diagnosis of HMB was related to the lower fitness-for-service score, history of bleeding, and dysmenorrhea. Daily activity and QoL were both affected by the severity of HMB and dysmenorrhea. Underdiagnosis of HMB and dysmenorrhea results from a combination of unawareness from the women's side and inattention from the system. In an era of female empowerment, each woman should be at the optimal physiological and psychological level to start her career; thus, addressing the menstrual burden and providing effective treatment is needed in the military scenario and other settings with demanding activities.

Under-Diagnosed and Under-Treated Menorrhagia in Young Women Produce Suboptimal Performance

Background: Menorrhagia can have a significant impact on a woman's life. It can lead to anemia, fatigue, difficulty with physical activities, absence from work, and avoidance of social activities and may be the first sign of a bleeding disorder. We presumed that many young women with menorrhagia do not seek medical advice or are under-treated. This study aimed to document the prevalence of menorrhagia, by questionnaire, visual scores and self-assessment; its association with bleeding disorders, and the effect of menorrhagia on activity and quality of life (QoL) in young adults engaged in compulsory military service. The military service in Israel is obligatory for women as for men, making this cohort similar to the general population. Method: In this cross-sectional study we gave a short oral lecture presenting the study objective and plan to female soldiers in combat and non-combat roles. Participants were asked to consent to complete a one page coded, unidentified, initial questionnaire. After providing an additional informed consent, study participants were asked to complete additional study questionnaires, including personal and family bleeding history, pictorial bleeding assessment chart (PBAC), dysmenorrhea questionnaire, and age-appropriate PedsQL™. All forms were coded with the same number as the initial questionnaire. PBAC scores above 100 were diagnostic for menorrhagia and above 200 signified severe menorrhagia. Results: Of 422 women soldiers completing the initial questionnaire, 365 (86.5%) completed all study questionnaires. Characteristics of women not completing all study questionnaires were similar to those with complete study data except there were more soldiers in a combat role in the former (P=0.02). The median (range, 25th-75th interval) of the PBAC score was 100 (4-590, 55-189). PBAC scores &amp;gt; 100 and 200 were reported by 181 (50%) and 81 (22%), respectively. Most participants correctly self-assessed menorrhagia; still, a high PBAC score was also recorded in some who answered "no" or "unknown" in the initial questionnaire (Figure 1). Diagnosis of menorrhagia was associated with a history of bleeding, specifically cutaneous and bleeding from the oral cavity (Figure 2), yet none of the participants reported a diagnosis of a known bleeding disorder. The use of NSAIDs during menstruation was associated with a higher rate of menorrhagia (Table 1). No association was found with the current army role. However, the diagnosis of menorrhagia was related to the pre-enrolment fitness ranking [a score reflecting the overall per-recruitment health status] (Table 1). Those with menorrhagia suffered from higher pain levels and moderate to severe negative effects on activity during the days of menstruation compared to those without menorrhagia (Table 1, Figure 3). A trend for lower QoL was found in those with menorrhagia (Table 1). Discussion: Menorrhagia in young adults is a significant clinical problem effecting activity and quality of life. It is under-recognized and under-treated. The association with other bleeding manifestations may suggest an under diagnosis of bleeding disorders. In a world of women empowerment, any treatable cause, leading to suboptimal performance should be addressed. Thus, assessment for menorrhagia and dysmenorrhea should be part of well-being visit also in young adults to provide appropriate management to reduce the undesired effects of menorrhagia. Disclosures Revel-Vilk: Takeda: Honoraria; sanofi-Genzyme: Honoraria; Pfizer: Honoraria.

Bleeding in Patients with Clinically Severe Von Willebrand Disease: Preliminary Results of Athn 9, a Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Severe Von Willebrand Disease (VWD)

Bleeding in Patients with Clinically Severe Von Willebrand Disease: Preliminary Results of Athn 9, a Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Severe Von Willebrand Disease (VWD)

Clinical significance of diagnostic algorithm in detection of mild hemostasis disorders in women with menorrhagia

Background/Aim. Coagulation disorders could be a cause of menorrhagia in women of reproductive age. The aim of the study was to estimate frequency of coagulation disorders and design an appropriate algorithm for detection of coagulation disorders. Methods. We investigated coagulation in 115 women (36.1 ? 9.6 years) with anamnestic data of menorrhagia, verified using semiquantitative method ? Pictorial Bleeding Assessment Chart (PBAC) with score ? 100. Results. Menorrhagia was objectively verified in sixty-four women (55.7%) and in comparison with those with normal menstruation they had higher PBAC score of menstrual cycle [median (Md) = 150.0 vs. Md = 50.0; p &lt; 0.001] but not its duration (7.2 ? 2.1 days vs. 7.3 ? 1.9 days; p &gt; 0.05). Coagulation defects was found in 12 (10.4%) women ? decreased F IX: Ac in 4 (3.5%), decreased F VII: Ac in 1 (0.9%), decreased F X: Ac in 1 (0.9%), decreased F XI: Ac in 1 woman (0.9%), while 5 (4.3%) women matched criteria for mild von Willebrand disease (VWD) type 1. Women with coagulation disorders had prolonged prothrombin time (PT) [Md = 13.1 s, range: 12.2?14.8 s vs. Md = 12.5 s, range 10.6?18.3 s; p = 0.032]. Anemia was diagnosed in 61 (53.0%) women. The strongest predictor of the hemostasis disorder was menorrhagia (Quotient of probability 0.018), then anemia presence (12.43), P? (2.35), menstrual cycle duration (1.16) and the PBAC score (0.98). Conclusion. The results of the study indicate the need to form a diagnostic algorithm for hemostasis disorders, primarily VWD. Sophisticated analysis of hemostasis is required, especially if predictive factors of statistical models are detected: objectively verified menorrhagia, anemia, prolonged menstrual cycle, PBAC score &gt; 100 and extended PT.

Heavy Menstrual Bleeding in Adolescent Females with Platelet Function Disorders

Background: Heavy menstrual bleeding (HMB) occurs frequently in adolescent females and a significant proportion have an underlying bleeding disorder. As diagnostic techniques for platelet function disorders (PFD) improve, these disorders are now recognized to commonly cause HMB and may be as prevalent as von Willebrand disease. Limited data exists about the prevalence of PFD in adolescents with HMB. Even less is reported on management and treatment outcomes in patients with HMB and PFD. HMB can negatively impact quality of life and cause serious adverse effects. In order to appropriately treat heavy menstrual bleeding in adolescent females with PFD, more information is needed about the prevalence, clinical manifestations, and management of these patients.Objectives: To evaluate the prevalence, clinical features, management, and outcomes of HMB in adolescent females with platelet function disordersMethods: A retrospective, single center chart review was performed of female patients aged 9-21 years with HMB and a diagnosed PFD treated at a tertiary care pediatric hospital from January 1, 2000 until December 31, 2017. Heavy menstrual bleeding was defined as menses lasting longer than 7 days, use of 8 or more pads or tampons per day during menstrual cycle, pictorial bleeding assessment chart score greater than 100, or symptomatic anemia. Patients were identified from our Hemophilia Treatment Center (HTC) registry, review of patients seen at a comprehensive clinic staffed by pediatric hematologists and gynecologists for adolescent females with HMB and bleeding disorders, and by an Electronic Medical Record (EMR) query of admission and discharge diagnoses of HMB and anemia. Data obtained included demographics, clinical features, laboratory results, treatment modalities, and outcomes.Results: 41 patients with PFD who achieved menarche were identified. 36 of these (88%) met criteria for HMB. The median age at presentation of HMB was 14 years (range 10-18). 35/36 patients had documented abnormal platelet aggregometry (PA) and the majority of patients (27/35) had at least 2 sets of abnormal PA. All patients were diagnosed with non-specific PFD. 15 of the 36 patients (41%) required hospitalization and packed red blood cell transfusion for severe anemia at time of presentation. Mean and median hemoglobin at presentation of HMB respectively were 9.5 gm/dL and 11.3 gm/dL (range 3.1-14.8) and 21 patients (58%) were anemic at presentation. 26 patients had ferritin obtained at presentation and 18 (69%) were iron deficient using our lab's reference range of ferritin less than 13 ng/dL. Half of the patients (18/36, 50%) failed first-line treatment. Successful first-line treatment included hormonal therapy alone (4 patients), hemostatic therapy alone with tranexamic acid (4 patients), hormonal plus hemostatic therapy (7 patients), and intra-uterine device plus hemostatic therapy (1 patient). The mean duration of HMB until report of resolution was 8.2 months (median 5 months; range 1-24). 8% (3/33) of patients reported continued HMB at last documented clinic visit.Conclusions: HMB occurred in the majority of adolescent female patients with PFD. These patients were frequently anemic and iron deficient. Severe and life-threatening anemia requiring hospitalization and packed red blood cell transfusion was common. First line treatment of HMB was not uniform and failed in 50% of the patients. Prospective studies are needed to standardize treatment of HMB in adolescents with PFD. DisclosuresCarpenter:Kedrion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria; CSL Behring: Speakers Bureau; Kane County State's Attorney: Consultancy; National Hemophilia Foundation (Impact Education): Speakers Bureau; HEMA Biologics: Consultancy; Novo Nordisk: Consultancy; Nationwide Children's Hospital: Speakers Bureau; American Academy of Pediatrics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech Incorporated: Membership on an entity's Board of Directors or advisory committees; Kedrion Biopharmaceuticals: Consultancy; 4th Judicial District Attorney's Office- Colorado: Consultancy; Novo Nordisk Pharmaceuticals, Inc: Consultancy.

Outcomes of Levonorgestrel Intrauterine System and Rollerball Ablation in Treatment of Menorrhagia

Aim: To compare the efficacy, safety and satisfaction of rollerball ablation (RBA) with that of levonorgestrel intrauterine system (LNGIUS) in control of heavy menstrual bleeding (HMB). Patients and Methods: An open label prospective randomized controlled trial was conducted between October 2014 and March 2017 in Benha University Hospital, Benha, Egypt. Eighty four Eligible women with functional HMB (Aged ≥ 35 years and ≤45 years, uterine size ≤ 10 weeks gestational size, uterocervical length ≤ 10 cm) were randomly assigned (1 : 1), 42 women in each group, to undergo RBA procedures or LNG- IUS insertions by closed envelops method and followed up to 24 months after the procedures. Themain outcomes were menstrual blood loss as assessed by pictorial bleeding assessment chart (PBAC) and hemoglobin values (g/dl) at 3, 6, 12, 24 months. Also, women satisfaction, patients quality of life were evaluated by questionnaire administered at 3, 6, 12, 24 months. Treatment modality side effects, safety and treatment failures were also assessed. Results: Both treatment modalities resulted in a significant reduction of PBAC scores and elevation of hemoglobin values. Also, both treatments were associated with higher significant satisfaction, and quality of life. Despite that the results in term of PBAC scores and in hemoglobin were initially with RBA, eventually both two treatmentmodalities shown no significant difference at 12, 24 months. Follow up both the treatment modalities were associated with comparable treatment failure rates (13%). Conclusions: Women treated with both LNG-IUS and RBA for HMB follow up to 24 months shows that both LNG - IUS and RBA were effective in control HMB as well as safe and associated with high level of satisfaction and better quality of life than to pretreatment period. Choice between this two treatment modalities should be based on surgeon skill and women preferences.

Identification of Qualitative Platelet Disorders in Adolescent Women with Heavy Menstrual Bleeding

Introduction: Nearly 40% of adolescent women experience heavy menstrual bleeding (HMB), and identifiable bleeding disorders are diagnosed in only 20-60% of these patients. We suspect that qualitative platelet disorders contribute to HMB, but are under-diagnosed. A pilot study was conducted to evaluate platelet function in adolescent women with HMB employing four novel, small-volume, whole blood platelet function assays. In addition, primary and secondary hemostasis, bleeding phenotype, and quality of life were assessed.Methods: Patients referred to the Young Women’s Hematology Clinic at Oregon Health & Science University for evaluation of HMB were offered participation in the study. Participants underwent standard review of their medical and family history and physical exam. Standard lab evaluation included CBC, PT, PTT, fibrinogen, thrombin time, Von Willebrand Panel, PFA-100, and iron studies with platelet aggregation or phenotyping performed if clinically indicated. Using less than 0.5 mL of whole blood, platelet function was assessed with four novel platelet function assays: assessment of platelet activation, secretion, and aggregation was assessed by flow cytometry analysis, while platelet adhesion and aggregation was assessed under shear in a capillary tube. Quality of life (QOL) was assessed using the PedsQL tool. Bleeding phenotype was assessed with the ISTH Bleeding Assessment Tool (ISTH BAT). Menorrhagia was assessed with the Pictorial Bleeding Assessment Chart (PBAC), the Philipp Tool and the clinical history.Results: Nine participants have enrolled on study to date, with 2 completing the 3-month visit. The median age of the cohort was 16 years (14-18 years). Eight out of nine categorized their period as heavy, 6 also had epistaxis, and 7 reported excessive bruising. The median ISTH BAT score was 4 (3-7). Of the 7 patients who had a Philipp Score obtained, 5 were positive. Median PBAC score was 161 (64-196). Median ferritin was 13 ng/mL (4-65 ng/mL). Median QOL psychosocial score was 70 (68.36-88.25), comparable to that of pediatric patients with cancer. Of the 9 participants, 6 had platelet aggregation and phenotyping. Four participants did not receive a bleeding disorder diagnosis, 1 was diagnosed with Type 1 VWD, 1 was diagnosed with bleeding disorder, NOS, and 1 was diagnosed with Ehlers Danlos Syndrome. Two participants were diagnosed with a qualitative platelet disorder (QPD): one based on platelet aggregation and one based on thromboelastography. The four novel platelet function assays confirmed platelet function abnormalities in the participants diagnosed with QPD’s (Figure 1&2). Impaired platelet response to agonist stimulation was also observed in participants with non-platelet disorder bleeding disorder diagnoses and in participants without a bleeding disorder diagnosis.Conclusions: In this pilot study, the etiology of HMB in adolescent women was evaluated with four novel platelet assays in addition to standard assays of hemostasis. A bleeding disorder diagnosis was not made with standard evaluations in 4 out of 9 participants. The novel assays detected platelet abnormalities not observed using currently available clinical labs, and confirmed the presence of abnormal platelet function in participants with abnormal platelet function testing. These assays require significantly less blood volume than currently available assays and expand investigation of platelet function to platelet adhesion and platelet interactions in whole and flowing blood. Further work is needed to determine the sensitivity and specificity of the novel assays in detecting platelet dysfunction. Continued investigation into the impact of HMB on the adolescent female population is needed. [Display omitted] [Display omitted] DisclosuresHaley:CSL Behring: Honoraria; Baxalta: Membership on an entity's Board of Directors or advisory committees. Recht:Biogen: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Biogen: Research Funding; Genentech: Research Funding; Novo Nordisk: Research Funding; Baxalta: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

Non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women with bleeding disorders.

Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common. This is an update of a previously published Cochrane Review. To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders. We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (25 August 2016), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013). Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder. Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias. Three cross-over studies, with 175 women were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported. Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.

One-Stage FVIII Activity Is Inversely Correlated with Heavy Menstrual Bleeding in Hemophilia a Carriers

IntroductionThe majority of carriers of hemophilia A have historically been considered to have normal hemostasis (FVIII:C >50%) and thus not have an increased bleeding tendency. However, our research group has demonstrated that some hemophilia A carriers can experience increased bleeding compared to normal women despite this normal FVIII activity. In our recently published study in adult hemophilia A carriers there was no correlation between FVIII:C, as measured by a one-stage coagulation assay, and bleeding phenotype, as measured by the MCMDM-1 VWD bleeding score. In this follow up study we sought to determine which of these hemophilia A carriers with normal FVIII:C are at risk for bleeding. The goal of this study is to determine the relationship between FVIII assays (one-stage and chromogenic) and thrombin generation with both menstrual bleeding and an overall bleeding tendency. MethodsWe recruited mothers of children with hemophilia A in the Emory University pediatric bleeding disorders clinic. We included only adult (>18 year of age) obligate hemophilia A carriers that did not have a concomitant bleeding disorder or chronic disease that would increase their bleeding tendency. We gathered basic demographic information and evaluated the overall bleeding tendency using the ISTH Bleeding Assessment Tool (ISTH BAT), a semi-quantitative assessment of bleeding scored from 0 to 56. We considered a score of 6 or higher consistent with pathologic bleeding. In addition, we inventoried menstrual bleeding with the Pictorial Bleeding Assessment Chart (PBAC), a visual representation of menstrual blood loss. We considered a PBAC greater than 100 consistent with heavy menstrual bleeding. Plasma samples were collected from each subject at the time of the survey in sodium citrate tubes without corn trypsin inhibitor. Samples were double spun at 2,500 rpm for 15 minutes and stored at -80°C.Laboratory evaluation for each subject included FVIII:C, measured by one-stage coagulation assay (aPTT reagent with micronized silica) and chromogenic assay (COATEST SP4 FVIII kit, Chromogenix), as well as thrombin generation (Calibrated Automated Thrombogram, PPP-Reagent Low, FluCa Kit) to evaluate endogenous thrombin potential (ETP, nM*min), peak thrombin (nM) and lag time (min). We performed linear regression using GraphPad Prism; p<0.05 was considered significant. ResultsOver a three-month period, we approached 32 adult obligate hemophilia A carriers; 23 agreed to participate in the survey, 16 consented to blood draw. One carrier was excluded in extreme outlier analysis and due to an autoimmune disorder, leaving 15 evaluable subjects. Our cohort is relatively young with a median age of 41 years (range 23-51), predominantly Caucasian (53%, 8/15) and the majority carry a severe mutation (10/15 severe, 2/15 moderate, 3/15 mild).Reproductive bleeding (post-partum hemorrhage and/or menstrual bleeding) was commonly reported (93%, 14/15). The median ISTH BAT bleeding score for subjects was 2 (range 1-8). The median PBAC score was 148 (range 10-608). The carriers had a relatively normal FVIII:C by one-stage assay with a median of 0.78 U/mL (range 0.30 - 1.06) and by chromogenic assay with a median of 1.15 U/mL (range 0.66 - 1.9). FVIIIC by one-stage assay was inversely correlated to PBAC (r2 =0.4; p=0.01, figure 1A). Conversely, FVIII:C by chromogenic assay did not correlate with PBAC, however trended toward significance (r2 = 0.19; p=0.10, figure 1A). Additionally, there was no correlation found between FVIII:C (one-stage or chromogenic assay) and ISTH BAT bleeding score (figure 1B). There was also no correlation found between bleeding score or PBAC and the parameters of the thrombin generation assay or between severity of the closest male relative's hemophilia and any of the assays performed. ConclusionsIn our cohort of adult obligate hemophilia A carriers, as the FVIII:C (one-stage assay) decreased, the menstrual bleeding tendency increased as measured by the PBAC. We were unable to find a correlation between other measures of hemostasis, including the chromogenic assay and thrombin generation, and commonly used bleeding assessment tools. Further larger studies are warranted to help determine which hemophilia A carriers would be at risk for bleeding. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A cross-sectional study of bleeding phenotype in haemophilia A carriers.

C), von Willebrand factor antigen level, ristocetin cofactor, platelet function analyser-100(TM) and ABO blood type. Forty-four haemophilia A carriers and 43 controls were included. Demographic features were similar. Laboratory results demonstrated a statistically significant difference only in C (82·5 vs. 134%, P<0·001). Carriers reported a higher number of bleeding events, and both condensed MCMDM-1 VWD bleeding scores (5 vs. 1, P<0·001) and PBAC scores (423 vs. 182·5, P=0·018) were significantly higher in carriers. Haemophilia A carriers exhibit increased bleeding symptoms when compared to normal women. Further studies are necessary to fully understand the bleeding phenotype in this population and optimize clinical management.

A clinical study assessing the efficacy of a new variant of the levonorgestrel intrauterine system for abnormal uterine bleeding

ObjectiveTo evaluate the efficacy and safety of a new variant of the levonorgestrel–intrauterine system (LNG-IUS)—Emily—for the treatment of abnormal uterine bleeding (AUB). MethodsA prospective, multicenter, single-arm, phase 4 study was conducted at six centers in India between July 2012 and August 2013. Eligible women were aged 30–50years, had completed their family, had AUB, and a pictorial bleeding assessment chart (PBAC) score of at least 100. After screening (visit 1) and insertion of the device (visit 2), participants were followed up at 1week, 1month, 3months, and 6months. The primary outcomes were menstrual blood loss (assessed by PBAC) and quality of life (assessed by the EQ-5D-3L questionnaire). ResultsAmong 63 participants, 45 (71%) completed the study. Mean PBAC score decreased from 238.0±128.7 at screening to 13.1±19.2 at 6months (P<0.001). EQ-5D-3L score increased from 79.0±14.1 at visit 2 to 86.3±9.0 at 6months (P=0.003). No serious adverse events related to the device were reported. ConclusionAmong women with AUB, use of the Emily LNG-IUS significantly reduces menstrual bleeding and improves quality of life.Clinical Trials Registry of India: CTRI/2012/07/002843

Non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women with bleeding disorders.

Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common. To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders. We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (13 March 2014), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013). Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder. Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias. Three cross-over studies, with 175 participants were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported. Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.

No increased systemic fibrinolysis in women with heavy menstrual bleeding

Bleeding disorders have been recognized as important etiologic or contributory factors in women with heavy menstrual bleeding. Fibrinolysis in the endometrium plays a role in heavy menstrual bleeding. It is unknown whether increased systemic fibrinolysis might also increase the risk of heavy menstrual bleeding. To investigate fibrinolytic parameters, including clot lysis time, in women with heavy menstrual bleeding. We included 102 patients referred for heavy menstrual bleeding (Pictorial Bleeding Assessment Chart score of > 100) in our cohort. Patients and controls (28 healthy volunteers without heavy menstrual bleeding) underwent hemostatic testing in the first week after menstruation. For 79 patients and all controls, fibrinolytic parameters (thrombin-activatable fibrinolysis inhibitor activity, and plasminogen activator inhibitor-1, tissue-type plasminogen activator and plasmin inhibitor levels) and clot lysis time were available. Fibrinolytic parameters were similar between patients and controls, except for thrombin-activatable fibrinolysis inhibitor (89.4% vs. 82.5%) and plasmin inhibitor (106% vs. 96%), the levels of which which were significantly higher in patients. In women with menorrhagia without gynecologic abnormalities, we found lower thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels than in women with gynecologic abnormalities (thrombin-activatable fibrinolysis inhibitor, 85.4% vs. 94.8%; plasminogen activator inhibitor-1, 16.0 μg L(-1) vs. 24.5 μg L(-1) ). Systemic fibrinolytic capacity is not increased in women with heavy menstrual bleeding. Overall, levels of the fibrinolytic inhibitors thrombin-activatable fibrinolysis inhibitor and plasmin inhibitor were even higher in patients than in controls. However, in a subgroup of women without gynecologic abnormalities, relatively lower levels of inhibitors may contribute to the heavy menstrual bleeding.

Levonorgestrel-releasing intrauterine system versus medical therapy for menorrhagia: a systematic review and meta-analysis.

BackgroundThe aim of this study was to compare the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) with conventional medical treatment in reducing heavy menstrual bleeding.Material/MethodsRelevant studies were identified by a search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and clinical trials registries (from inception to April 2014). Randomized controlled trials comparing the LNG-IUS with conventional medical treatment (mefenamic acid, tranexamic acid, norethindrone, medroxyprogesterone acetate injection, or combined oral contraceptive pills) in patients with menorrhagia were included.ResultsEight randomized controlled trials that included 1170 women (LNG-IUS, n=562; conventional medical treatment, n=608) met inclusion criteria. The LNG-IUS was superior to conventional medical treatment in reducing menstrual blood loss (as measured by the alkaline hematin method or estimated by pictorial bleeding assessment chart scores). More women were satisfied with the LNG-IUS than with the use of conventional medical treatment (odds ratio [OR] 5.19, 95% confidence interval [CI] 2.73–9.86). Compared with conventional medical treatment, the LNG-IUS was associated with a lower rate of discontinuation (14.6% vs. 28.9%, OR 0.39, 95% CI 0.20–0.74) and fewer treatment failures (9.2% vs. 31.0%, OR 0.18, 95% CI 0.10–0.34). Furthermore, quality of life assessment favored LNG-IUS over conventional medical treatment, although use of various measurements limited our ability to pool the data for more powerful evidence. Serious adverse events were statistically comparable between treatments.ConclusionsThe LNG-IUS was the more effective first choice for management of menorrhagia compared with conventional medical treatment. Long-term, randomized trials are required to further investigate patient-based outcomes and evaluate the cost-effectiveness of the LNG-IUS and other medical treatments.

The prevalence of underlying bleeding disorders in patients with heavy menstrual bleeding with and without gynecologic abnormalities

The purpose of this study was to assess the prevalence of underlying bleeding disorders in women with heavy menstrual bleeding (HMB) with and without gynecologic abnormalities. We performed a single-center prospective cohort study of 112 consecutive patients who were referred for heavy menstrual bleeding. Control subjects were 28 healthy volunteers who reported no HMB. Patients and control subjects had hemostatic testing in the first week after menstruation. Patients underwent gynecologic evaluation. The median age was 42.5 years (range, 17-55 years) in patients and 40.0 years (range, 25-55 years) in control subjects. Forty-six percent of patients had anemia; the median pictorial bleeding assessment chart score was 271. Seven percent of the control subjects with a subjectively normal menstruation had anemia. Twenty-six percent of patients had gynecologic abnormalities, which was considered to explain HMB. Overall, we found an underlying bleeding disorder in 29% of the patients, which was comparable for unexplained and explained HMB (31% vs 27%; P= .75). We diagnosed 6cases of Von Willebrand's disease, 4 cases of factor XI deficiency, and 1 case of factor VII deficiency. The only abnormalities that we found in control subjects were platelet aggregation defects (11% in control subjects vs 23% in patients). Patients had a significantly longer activated partial thromboplastin time compared with control subjects (26.5 vs 25.0 seconds; P= .001) that was caused by lower median levels of factor XI (100 vs 124 IU/dL; P < .001). Bleeding disorders play an equally important role in the cause of both unexplained and explained heavy menstrual bleeding. A novel finding is the occurrence of low, but not deficient, levels of factor XI.

Laparoscopic Occlusion Compared With Embolization of Uterine Vessels

To compare clinical outcome 6 months after treatment with bilateral laparoscopic occlusion of the uterine artery versus uterine leiomyoma embolization. Sixty-six premenopausal women with symptomatic uterine leiomyomata were randomized to treatment with either laparoscopic occlusion of uterine arteries or uterine leiomyoma embolization. The primary outcome was reduction of blood loss from pretreatment to 6 months postoperatively, measured by a Pictorial Bleeding Assessment Chart. Secondary outcomes included patients' own assessment of symptom reduction, postoperative pain assessed using visual analog scales, ketobemidone used postoperatively, complications, secondary interventions, and failures. Fifty-eight women were included; 6-month follow-up data were available for 28 participants in each group. The percentage reduction in Pictorial Bleeding Assessment Chart scores did not differ between the treatment groups (52% after uterine leiomyoma embolization and 53% after laparoscopy, P=.96). The study had 52% power to detect a 20% difference on the Pictorial Bleeding Assessment Chart. Fewer participants in the group treated with uterine leiomyoma embolization complained of heavy bleeding after 6 months (4% compared with 21%, P=.044). The postoperative use of ketobemidone was higher after uterine leiomyoma embolization (46 mg compared with 12 mg, P<.001). Both laparoscopic occlusion of uterine vessels and embolizaton of uterine leiomyoma improved clinical symptoms in the majority of patients. Participants with the laparoscopic procedure had less postoperative pain but heavier menstrual bleeding 6 months after treatment. A larger study and longer follow-up is necessary before a definite conclusion can be made regarding the most effective treatment. (www.ClinicalTrials.gov), NCT00277680 I.

A randomised trial comparing the levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding

To compare the levonorgestrel intrauterine system (LNG-IUS) (Mirena); Schering Co., Turku, Finland) and thermal balloon ablation (Thermachoice; Gynecare Inc., Menlo Park, CA, USA) for the treatment of heavy menstrual bleeding. An open, pragmatic, prospective randomised trial. A menstrual disorders clinic at National Women's Hospital, Auckland, New Zealand. Seventy-nine women with heavy menstrual bleeding randomised to the LNG-IUS (40 women) or the thermal balloon ablation (39 women). Women were randomised to treatment with the LNG-IUS or thermal balloon ablation and followed up by a postal and telephone questionnaire. Menstrual loss measured by a pictorial bleeding assessment chart (PBAC) at 3, 6, 12 and 24 months. Patient satisfaction, quality of life and menstrual symptoms were assessed by questionnaire administered at 3, 6, 12 and 24 months. Treatment side effects and treatment failures were also recorded. Both the treatments resulted in a significant reduction in PBAC scores. At 12 and 24 months, median PBAC scores were significantly lower in women treated with the LNG-IUS compared with women treated by thermal balloon ablation (11.5 versus 60.0 at 12 months [P= 0.002]; 12.0 versus 56.5 [P= 0.002] at 24 months). At 24 months, nine (35%) women still using the LNG-IUS had amenorrhoea compared with one (5%) woman successfully treated by thermal balloon ablation (P = 0.025). There were no significant differences in patient satisfaction between two treatments during follow up. Treatment failed in 11 (28%) women using the LNG-IUS and in 10 (26%) women treated with thermal balloon ablation. Overall, women in both groups showed an increased quality of life as a result of the treatment, with Short Form-36 scores increasing from 63.7 at randomisation to 76.1 at 24 months. At 12 and 24 months of follow up, women with heavy menstrual bleeding treated with the LNG-IUS have significantly lower PBAC scores than women treated with thermal balloon ablation. Both the treatments resulted in a significant increase in overall quality of life, but there were no significant differences between either treatment in quality of life, patient satisfaction or the number of women requesting an alternative treatment during 24 months of follow up.