Pictorial Blood Assessment Chart Research Articles

High-intensity focused ultrasound for endometrial ablation in adenomyosis: a clinical study.

The present study aimed to investigate the clinical efficacy of endometrial ablation with high-intensity focused ultrasound (HIFU) for symptom relief in women with adenomyosis. Between July 2014 and July 2020, 167 patients with adenomyosis treated at the Zhongshan City People's Hospital were enrolled in this study. Patients were divided into two groups according to patient aspirations: the control group, including patients who only underwent ablation of adenomyosis lesions (group A) and the treatment group, including patients who underwent removal of adenomyosis lesions and endometrial ablation (group B). The reduced dysmenorrhea scores (visual analog scale) and menstrual volume scores (pictorial blood assessment chart) were measured before and after treatment. The scores were obtained by subtracting the postoperative scores from the preoperative scores and were compared to determine whether the symptoms had alleviated. Compared with the menstrual volume of group A, that in group B showed significant improvements. The average relief rates of dysmenorrhea in the two groups also showed significant improvement. However, the scores in group B showed a more significant improvement than those in group A. Therefore, our findings suggest that endometrial ablation using HIFU may be superior to conventional therapy with regard to alleviating the symptoms of increased menstruation in women with adenomyosis.

Efficacy of Regular Prophylaxis with a Plasma-Derived Von Willebrand Factor/Factor VIII Concentrate in Reducing Heavy Menstrual Bleeding in Females with Von Willebrand Disease

Background: Heavy menstrual bleeding (HMB) is the dominant symptom affecting ~80-90% of women with VWD and is a common cause of outpatient visits and hospitalizations. Long-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in von Willebrand disease (VWD) patients with a history of severe, frequent bleeds, and for women with VWD who experience HMB. A recent prospective study found that recombinant VWF was not superior to tranexamic acid at reducing HMB in women with VWD. The WIL-31 study demonstrated the efficacy of prophylaxis with a plasma-derived VWF/factor VIII (pdVWF/FVIII) concentrate containing VWF and FVIII in a 1:1 activity ratio (wilate ®) in adults and children with VWD of all types. The primary endpoint was met, showing a decrease of 84% in the mean total annualized bleeding rate (ABR) compared with prior on-demand treatment. The impact of pdVWF/FVIII prophylaxis on HMB was evaluated as a secondary endpoint of the WIL-31 study. Aims: To investigate the efficacy of regular prophylaxis with a pdVWF/FVIII concentrate in reducing the incidence of HMB in females with VWD who had previously been treated on demand. Methods: WIL-31 (NCT04052698) was a prospective, non-controlled, international, multicenter phase 3 trial that enrolled male/female patients, aged ≥6 years old with VWD type 1 (VWF:RCo <30 IU/dL), type 2 (except 2N) or type 3. Prior to entering the WIL-31 study, all patients had received on-demand treatment with a VWF-containing product during a 6-month, prospective, observational, run-in study (WIL-29). Patients in WIL-31 received regular pdVWF/FVIII prophylaxis 2-3 times per week at a dose of 20-40 IU/kg for 12 months. Exploratory analyses included comparison of heavy menstrual ABR (HMABR). HMB was defined as any menstrual bleed that impeded the ability to perform daily activities (such as work, housework, exercise, or social activities) during menstrual periods. Criteria for HMB included changing pads more frequently than hourly, menstrual bleeding lasting 7 or more days, or the presence of clots >1 cm combined with a history of flooding or a Pictorial Blood Assessment Chart (PBAC) score ≥185. PBAC scores were reviewed from patient diaries at each study visit. Results: Of the 33 patients included in the overall population, 14 (42%) were female and half (n=7; 13-43 years old) were of childbearing age. In these females, all VWD types were represented: type 1 (n=2), type 2 (n=1); and type 3 (n=4). Six (86%) females were on hormonal birth control during WIL-31. Prophylaxis with pdVWF/FVIII reduced the mean HMABR by 64% compared with on-demand treatment (3.0 vs 8.3 in WIL-31 and WIL-29, respectively). During on-demand treatment, 86% (6/7) of females experienced ≥1 HMB episode, which was reduced to 29% (2/7) during prophylaxis with four patients experiencing no HMB (Figure 1). During on-demand treatment, 6 females experienced 32 HMB episodes; of these, 7 (22%) required further treatment with pdVWF/FVIII and 2 (6%) required concomitant medication. Under prophylaxis, two patients (aged ≥17 years), experienced 12 HMBEs; of these, only one (8%) impeded daily activity and none required additional pdVWF/FVIII treatment, hospitalization, or concomitant medication. Mean (SD) intra-individual median PBAC scores (N=4) decreased by 43% from 227 (91.7) during on-demand treatment to 131 (59.9) with prophylaxis, a 96-point reduction. Conclusion: Prophylaxis with pdVWF/FVIII was efficacious in reducing HMB compared with on-demand treatment in 7 female patients with VWD. None of the cases of HMB during prophylaxis was severe enough to require additional treatment. Among women with VWD, HMB remains a major burden and further research is required.

The ISTH-BAT score and outcomes after endometrial ablation in women with heavy menstrual bleeding.

The International Society on Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT), is used during the diagnostic workup of bleeding disorders. Data on ISTH-BAT scores in women with heavy menstrual bleeding (HMB) undergoing endometrial ablation (EA) could be essential in optimizing HMB counselling. To investigate the postsurgical incidence of amenorrhea, dysmenorrhea, quality of life, re-intervention after EA, and ISTH-BAT score. This study included women who have undergone EA because of HMB. During a follow-up of 2 to 5 years, ISTH-BAT, pictorial blood assessment chart (PBAC), and Short Form-36 survey (SF-36) were administered. At 10 years of follow-up surgical re-interventions were evaluated. Seventy-one women were included of whom 77% (n=55) had an ISTH-BAT score<6, versus 23% (n=16) ISTH-BAT score ≥6 (mean age 46.3versus 42.3, p=0.004). In the ISTH-BAT ≥6 group versus<6 group, amenorrhea occurred in 63% (10/16) versus 82% (45/55) (p=0.111), dysmenorrhea in 38% (6/16) versus 18% (10/55) (p=0.111), and surgical re-intervention in 19% (3/16) versus 25% (14/55) (p=0.582). SF-36 item (Bodily) pain was lower in the ISTH-BAT ≥6 group versus <6 (median score 58.7vs. 80.0, p=0.104). An ISTH-BAT score ≥6 may be related to a lower amenorrhea incidence and higher dysmenorrhea rate after EA.

Bleeding profile and safety of a levonorgestrel 13.5 mg intrauterine device versus Nova T copper 380 mm2 intrauterine device: Results of a 3-year, single-center, randomized phase 4 study

ObjectiveTo assess the bleeding profiles of the levonorgestrel 13.5 mg intrauterine device (LNG13.5-IUD) and Nova T copper 380 mm2 IUD (Cu380-IUD). Study designSingle-center, evaluator-masked, randomized study conducted in women aged 18–45 years starting these methods. Primary outcomes were number of bleeding days, self-reported bleeding intensity, Pictorial Blood Assessment Chart (PBAC) score, and blood biochemical values at baseline, months 3, 6, 12, 24, and 36 per 90-day reference periods except for PBAC (months). Secondary objectives were presence/duration/intensity of dysmenorrhea and tolerability. ResultsWe included 106 women aged 32.5 ± 6.7 years: 55 with LNG13.5-IUD and 51 with Cu380-IUD. Data for LNG13.5-IUD versus Cu380-IUD at baseline and month 36 (both respectively) were as follows: (1) median (25th; 75th percentile) number of bleeding days: 12 (9.0; 15.0) versus 12 (9.0; 15.0), p = 0.82, and 4 (0; 13.7) versus 15 (14.2; 20.0), p < 0.001; (2) mean bleeding intensity: 1.7 for both, p = 0.66, and 0.7 and 2.2, p < 0.001. Forty percent versus 0% presented with amenorrhea at month 36; (3) mean PBAC score (95% Confidence interval (CI): 50.7 (16.6; 84.7) versus 130.4 (95.7; 165.0) at month 1, and 7.9 (−26.7; 42.6) versus 126 (90.7; 161.2), p < 0.001; (4) median (25th; 75th percentile) ferritin levels (Ug/L) 33 (19; 53) versus 30 (19; 45), p = 0.70, and 59 (42; 84) versus 21 (8; 39). We did not observe changes or differences between groups in hemoglobin and hematocrit. The duration and intensity of dysmenorrhea were significantly lower with LNG13.5-IUD versus Cu380-IUD. Adverse events were those expected. ConclusionsLNG13.5-IUD is associated with a significant reduction in blood loss and dysmenorrhea compared with Cu380-IUD. ImplicationsWomen eligible for a levonorgestrel 13.5 mg intrauterine device (IUD) or a copper 380 mm2 IUD should be informed of the differences in bleeding profiles—one of the main causes for IUD discontinuation—so they can compare this information against their bleeding expectations.

Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial

Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding. We aimed to compare recombinant VWF with tranexamic acid for reducing heavy menstrual bleeding in patients with von Willebrand disease. VWDMin, a phase 3, open-label, randomised crossover trial, was done in 13 haemophilia treatment centres in the USA. Female patients aged 13-45 years with mild or moderate von Willebrand disease, defined as VWF ristocetin cofactor less than 0·50 IU/mL, and heavy menstrual bleeding, defined as a pictorial blood assessment chart (PBAC) score more than 100 in one of the past two cycles were eligible for enrolment. Participants were randomly assigned (1:1) to two consecutive cycles each of intravenous recombinant VWF, 40 IU/kg over 5-10 min on day 1, and oral tranexamic acid 1300 mg three times daily on days 1-5, the order determined by randomisation. The primary outcome was a 40-point reduction in PBAC score by day 5 after two cycles of treatment. Efficacy and safety were analysed in all patients with any post-baseline PBAC scores. The trial was stopped early due to slow recruitment on Feb 15, 2022, by a data safety monitoring board request, and was registered at ClinicalTrials.gov, NCT02606045. Between Feb 12, 2019, and Nov 16, 2021, 39 patients were enrolled, 36 of whom completed the trial (17 received recombinant VWF then tranexamic acid and 19 received tranexamic acid then recombinant VWF). At the time of this unplanned interim analysis (data cutoff Jan 27, 2022), median follow-up was 23·97 weeks (IQR 21·81-28·14). The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146 [95% CI 117-199] vs 213 [152-298]; adjusted mean treatment difference 46 [95% CI 2-90]; p=0·039). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs zero during recombinant VWF treatment) and other bleeding (four [6%] vs two [3%]). These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience. National Heart Lung Blood Institute (National Institutes of Health).

Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

The effect of vitamin D on the severity of dysmenorrhea and menstrual blood loss: a randomized clinical trial

BackgroundPrimary dysmenorrhea is considered as one of the women’s main problems during reproductive age. The present study aimed to investigate the effect of vitamin D on the severity of dysmenorrhea and menstrual blood loss.MethodsThis double-blind, randomized, placebo-controlled trial, was performed on 84 single female college students between 18 and 25 years old who living in dormitories. Students with primary dysmenorrhea and vitamin D deficiency were divided into experimental (n = 42) and control (n = 42) groups. Five days before the putative beginning of their next menstrual cycle, the experimental group received 300,000 IU vitamin D (50,000 IU, two tablets every 8 h), and the control group received a placebo (oral paraffin). The effects of the supplement on the severity of dysmenorrhea and menstrual blood loss were evaluated one cycle before and during two successive cycles. Using the visual analog scale (VAS), verbal multidimensional scoring system (VMS), and pictorial blood assessment chart (PBLAC) questionnaires. Fisher’s exact, Chi-square, independent sample t-test and repeated measurements were used.ResultsIn total, 78 of the 84 students completed the study (39 students per group). The intervention resulted in a significant reduction in the mean scores of both the VAS and VMS in the experimental group, in the first and second menstrual cycles (p < 0.001, p < 0.001, respectively), but not in the means score of PBLAC. Mefenamic acid consumption at the first and second menstruation period, in the experimental group was lower than the control group (p = 0.009, p < 0.001, respectively).ConclusionsThe results indicate that vitamin D supplementation could decrease the severity of primary dysmenorrhea and the need to consume pain-relief medications. Contrariwise vitamin D supplementation had no significant effect on menstrual blood loss.Trial registrationThis trial was registered in the Iranian Registry of Clinical Trials with code IRCT201305212324N on 18/1/2014. URL of registry: https://en.irct.ir/trial/1964.

Treatment of abnormal uterine bleeding using levonorgestrel-releasing intrauterine devices: experience from a Turkish tertiary hospital.

We evaluated the efficacy of the levonorgestrel-releasing intrauterine device in treating menorrhagia using a pictorial blood assessment chart. We retrospectively examined 822 patients treated with a levonorgestrel-releasing intrauterine device for abnormal uterine bleeding between January 1, 2017, and December 31, 2020, at a Turkish tertiary hospital. A pictorial blood assessment chart was used to determine each patient's blood loss amount, which involves the use of an objective scoring system to determine the amount of bleeding in towels, pads, or tampons. Descriptive statistical values were presented as mean and standard deviation, and paired sample t-tests were used for within-group comparisons of normally distributed parameters. Moreover, in the part of the descriptive statistical analysis, the mean and median values for the non-normally distributed tests were not close to each other, indicating that the data obtained and analyzed in this study had a non-normal distribution. Of 822 patients, 751 (91.4%) exhibited a significant reduction in menstrual bleeding after device insertion. Moreover, a significant decrease was observed in the pictorial blood assessment chart scores 6 months postoperatively (p < 0.05). This study revealed that the levonorgestrel-releasing intrauterine device is an easy-to-insert, safe, and effective treatment option for abnormal uterine bleeding (AUB). Furthermore, the pictorial blood assessment chart is a simple and reliable tool for evaluating menstrual blood loss in women before and after the insertion of levonorgestrel-releasing intrauterine devices.

How do anticoagulants impact menstrual bleeding and quality of life? - The PERIOD study

BackgroundThere is increasing recognition that menstruating women prescribed anticoagulants experience heavy menstrual bleeding. ObjectivesThe aim of this study is to report the extent of bleeding in menstruating women after commencing anticoagulants and the impact it has on their quality of life. MethodsWomen aged 18 to 50, initiated on anticoagulant therapy, were approached to take part in the study. In parallel, a control group of women was also recruited. Women were asked to complete the menstrual bleeding questionnaire and a pictorial blood assessment chart (PBAC) during their next 2 menstrual cycles. Differences between the control and anticoagulated group were compared. Significance was considered at < .05. Ethics committee approval: REC reference: 19/SW/0211. ResultsFifty-seven women in the anticoagulation and 109 women in the control group returned their questionnaires. Women in the anticoagulated group reported an increase in the median length of their menstrual cycle from 5 to 6 days after commencing anticoagulation, compared to 5 days for women in the control group (P < .05). Anticoagulated women reported significantly higher PBAC scores as compared to the control group (P < .05), with two-thirds of women in the anticoagulation group reporting heavy menstrual bleeding. Women in the anticoagulation group reported worsening quality of life scores following the initiation of anticoagulation, compared with women in the control group (P < .05). ConclusionHeavy menstrual bleeding occurred in two-thirds of women commencing anticoagulants, who completed a PBAC, which had negative impact on their quality of life. Clinicians commencing anticoagulation therapy should be mindful of this, and recognized measures should be taken to help minimize this problem for menstruating individuals.

Assessing a cut-off point for the diagnosis of abnormal uterine bleeding using the Menstrual Bleeding Questionnaire (MBQ): a validation and cultural translation study with Brazilian women.

Abnormal uterine bleeding (AUB) is a common condition, and the Menstrual Bleeding Questionnaire (MBQ) is used for its assessment. To translate, assess the cut-off point for diagnosis, and explore psychometric properties of the MBQ for use in Brazilian Portuguese. Prospective cohort study including 200 women (100 with and 100 without AUB) at a tertiary referral center. MBQ translation involved a pilot-testing phase, instrument adjustment, data collection, and back-translation. Cut-off point was obtained using receiver operating curve analysis. Menstrual patterns, impact on quality of life due to AUB, internal consistency, test-retest, responsiveness, and discriminant validity were assessed. For construct validity, the Pictorial Blood Assessment Chart (PBAC) and World Health Organization Quality of Life - abbreviated version (WHOQOL-BREF) were applied. Women with AUB were older, had higher body mass indices, and had a worse quality of life during menstruation. Regarding the MBQ's psychometric variables, Cronbach's alpha coefficient was > 0.70 in all analyses, high intraclass correlation coefficient was found in both groups; no ceiling and floor effects were observed, and construct validity was demonstrated (correlation between MBQ score, PBAC score, and clinical menstrual cycle data). No difference between MBQ and PBAC scores were perceived after the test-retest. Significant differences were found between MBQ and PBAC scores before and after treatment. An MBQ score ≥ 24 was associated with a high probability of AUB; accuracy of 98%. The MBQ is a reliable questionnaire for Brazilian women. The cut-off ≥ 24 shows high accuracy to discriminate AUB.

To Study the Efficacy and Safety of Diosmin with Tranexamic Acid and Mefenamic Acid Versus only Tranexamic Acid and Mefenamic Acid in Medical Management of Abnormal Uterine Bleeding: A Randomized Controlled Trial.

Abnormal uterine bleeding (AUB) is a common problem in reproductive age group and perimenopausal age group being responsible for many outpatient visits. Traditional management of AUB consists of giving mefenamic acid, tranexamic acid, or their combination with progestogens or hormonal intrauterine deviced levonorgestrel intrauterine system (LNG-IUS) for severe or nonresponsive cases. The objective of the current study was to study the efficacy and safety of adding diosmin along with tranexamic acid and mefenamic acid in reducing menstrual blood loss in AUB patients. It was a prospective double-blind randomized controlled trial in which 900 mg of diosmin was given once daily along with 500 mg tranexamic acid and 250 mg mefenamic acid during menstruation (Group I-92 patients), or only tranexamic acid and mefenamic acid during menstruation (Group II-92 patients). Mean age, parity, body mass index, and socioeconomic status were similar in the two groups. It was 35.68 years versus 36.78 years, 2.2 versus 2.3, 23.68 kg/m2 versus 24.62 kg/m2 respectively. Mean days of bleeding before this treatment were 6.8 versus 6.6 (P = 0.33) and were 3.5 versus 5.2 (P = 0.02) after treatment. There was a significant reduction in both groups as compared to before treatment (P = 0.021 in Group I, 0.027 in Group II) but the reduction was greater in Group I (P = 0.02). The amount of blood loss was 385 ml versus 390 ml (P = 0.7) before treatment which was significantly reduced in both groups to 68 ml versus 112 ml (P = 0.02 in Group I, 0.03 in Group II) with more decrease in Group I than in Group II (P = 0.01). Mean hemoglobin at beginning of the study was 8.4 versus 8.5 g/dl in Group I and Group II (P = 0.02) and significantly increased in both groups posttreatment to 10.9 and 9.8 g/dl in Group I and Group II (P = 0.012 in Group I, 0.011 in Group II) with increase being more in Group I than Group II (P = 0.03). Pictorial blood assessment chart score was 398 versus 406 (P = 0.35) before treatment and decreased significantly to 86.5 and 110.5 (P = 0.001 in Group I, 0.001 in Group II) with more decrease being in Group I than II (P = 0.01). There was significant decrease in dysmenorrhea with both treatments with no difference in the two groups. Various adverse effects such as nausea, vomiting, abdominal pain, diarrhea, constipation, and headache were equal in the two groups. Both the group's diosmin with tranexamic acid and mefenamic acid (Group I) and tranexamic acid and mefenamic acid (Group II) were efficacious in reducing menstrual blood loss, number of menstrual days and dysmenorrhea with effect being more by addition of diosmin. Adverse effects were equal in both the two groups.

The Empower Study - Design of a Randomized Clinical Trial to Assess the Efficacy and Safety of a Plasma-Derived Von Willebrand Factor / Factor VIII Concentrate for Heavy Menstrual Bleeding in Women with Von Willebrand Disease

Background: Although von Willebrand disease (VWD) is inherited by men and women equally, women are more likely to experience bleeding symptoms due to the challenges of menstruation and childbirth. Heavy menstrual bleeding (HMB) is the most common symptom observed in women and girls with VWD, and increases risk of iron deficiency anemia, blood transfusion, hospitalization and decreased health-related quality of life. While replacement therapy with von Willebrand factor (VWF) is recommended for prophylaxis in patients with VWD with severe and frequent bleeding, recommendations on its use for prophylaxis of HMB are limited due the lack of clinical trial data. Aims: The EMPOWER pilot trial will determine the feasibility of the trial design, as well as explore assay sensitivity to inform the determination of the primary outcome for the definitive randomized trial which will evaluate the effect of prophylaxis with plasma-derived VWF/FVIII (1:1; pdVWF:FVIII) concentrate compared with placebo on HMB in women with VWD. Methods: EMPOWER is a pilot, randomized, placebo-controlled, crossover, double-blind (patient and outcome assessor blinded), 2-year trial in female outpatients with VWD and HMB. We will evaluate the effect of 2-3 doses of prophylaxis with 40-60 IU VWF:RCo/kg pdVWF/FVIII concentrate when provided on the 2 heaviest days within the first 4 days of menstruation compared with placebo (normal saline). For the first treatment period, participants will be randomized to receive either pdVWF/FVIII concentrate or placebo for 4 cycles, crossing over to the comparator treatment during the second treatment period (see Figure 1). Non-pregnant female patients, ≥18 years of age with a diagnosis of inherited VWD (any type) with HMB defined as a modified pictorial blood assessment chart (mPBAC) score >100, on stable treatment for HMB and iron-deficiency anemia will be eligible. Patients with diagnosis of another bleeding disorder or the presence of >2 risk factors for venous thromboembolism will be excluded. The pilot trial viability outcomes include blinding index scores and participant drop-out rates. Feasibility outcomes include data completeness and rate of enrolment. The proposed primary clinical efficacy outcome is the mPBAC score and the key secondary efficacy outcome is the need for rescue therapy (i.e. >2 days of oral tranexamic acid use, additional treatment with pdVWF:FVIII concentrate, additional hormonal therapy for HMB, urgent/emergent gynecological surgery for HMB, treatment with intravenous iron, red blood cell transfusion, or hospital admission for HMB). Other secondary outcomes include major bleeding, clinically relevant non-major bleeding, red blood cell transfusion, fatigue and quality of life scores. Given the uncertainty in this area of research and the relative comparable clinical importance of proposed clinical efficacy outcomes, we will evaluate assay sensitivity to determine the outcome that has the greatest chance of detecting a difference between treatment periods. Assay sensitivity is defined as the ability of a scale to distinguish an effective from a less effective intervention or placebo. Assay sensitivity along with the proportion of missing data per clinical efficacy outcome and sample size considerations will influence the choice of primary outcome for the definitive trial. Safety will be evaluated by monitoring for hypersensitivity reactions, thromboembolic events and VWF inhibitors. The pilot trial will recruit 20 participants from Hemophilia Treatment Centres in Canada over 2 years. Results: The pilot trial is aiming to launch by the fall 2022. If the pilot trial is deemed feasible and viable, we will subsequently conduct a definitive international randomized controlled trial. Conclusion: Data from the EMPOWER trial will fill an important knowledge gap to facilitate evidence-based management of HMB in women with VWD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use.

Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use.

The effect of transcervical resection of submucous fibroids on menstrual blood loss: A prospective cohort study

ObjectivesTranscervical resection of myoma (TCRM) is a widely implemented treatment for submucous fibroids. The aim of this study is to evaluate the effect of TCRM on menstrual bleeding, fibroid related symptoms and quality of life and hemoglobin (Hb) levels. Study designA prospective cohort study was conducted in three teaching hospitals and two academic hospitals in the Netherlands. Patients with HMB (PBAC score > 150) and submucous fibroids (type 0, 1, 2, 3, 4 and hybrid type 2–5) scheduled for TCRM were eligible. At baseline and 3 months after TCRM a Trans Vaginal Ultrasound (TVU) was performed and a Hb sample was taken. Patients filled out the Pictorial Blood Assessment Chart (PBAC) and the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire at baseline and up to 6 months after surgery. Primary outcome was improvement in PBAC score 6 months after surgery. Secondary outcomes were improvement in PBAC score and Hb level 3 months after surgery and UFS-QOL scores 3 and 6 months after surgery. Results126 patients were included and 104 were operated. PBAC were obtained from 98 patients. Six months after surgery, 56.6% of patients went from HMB to normal menstrual bleeding (PBAC < 150). A significant reduction in median PBAC scores of 427 (IQR 198 – 1392) (p <.0001) was found (86% improvement). UFS-QOL scores were obtained from 91 patients. Symptom severity improved from a median of 54 on a scale of 100 (IQR 44–66) at baseline to 22 (IQR 9–41) after 6 months (p <.0001) (59% improvement). Health related quality of life (HRQOL) improved from a median score of 44 on a scale of 100 (IQR 33–62) to 89 (IQR 67–97) 6 months after surgery (p <.0001) (102% improvement). ConclusionTCRM significantly reduces the amount of menstrual bleeding, severity of fibroid related symptoms and improves HRQOL in patients with submucous fibroids.

Could the anatomic location of Essure® device explain the impairment of quality of life?

Since health-related quality of life (HRQL) could improve after removal of Essure® (Bayer, Leverkusen, Germany) inserts in symptomatic patients, we aimed to assess whether such postoperative enhancement was linked to the anatomic placement of the device. Correct and incorrect placed Essure® (Bayer) were identified in the electronic database of the French cohort Ablimco (cohort of consenting patients with laparoscopic Essure® [Bayer] removal). HRQL, pain and heavy menstrual bleeding were evaluated after Essure® (Bayer) removal with validated quality of life questionnaires (Short Form12 Questionnaire, Visual Analogue Scale, French version of the McGill Pain Questionnaire and the pictorial blood assessment chart PBAC). Sixty-five patients were included in the study divided in two groups (group A with correct placement: 45 patients and group B with incorrect placement: 20 patients). HRQL and Pain Index were improved in both groups at 6 months post-surgery. There was not any statistically significant difference between group A and B. The PBAC score increased at 6 months postoperatively in group A and B without any statistically significant difference between them. Postoperative improvement of quality of life and pain index was similar whatever the position of the implant. This suggests that symptomatology and quality of life are not related to the anatomic location of the Essure® (Bayer) implants.

Effectiveness of Levonorgestrel Releasing Intrauterine System in Perimenopausal Women with Heavy Menstrual Bleeding: A Prospective Study at a Teaching Hospital in India.

To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on heavy menstrual bleeding in perimenopausal women. This was a prospective, observational clinical study conducted on 42 perimenopausal women with heavy menstrual bleeding who met the study eligibility criteria. LNG-IUS was inserted in the postmenstrual phase following baseline evaluation. The patients were followed up at the 4, 12, and 24 weeks. Pictorial blood assessment chart (PBAC) score, hemoglobin and serum ferritin levels, and endometrial thickness were assessed before insertion and during the follow-up visits. Two patients (4.8%) were lost to follow-up, three patients (7.1%) opted for hysterectomy, two women (4.8%) experienced spontaneous expulsion and 35 (83.3%) women continued the usage. Menstrual blood loss assessed using the median PBAC score (interquartile range) significantly reduced (P < 0.001) from the pre-insertion level of 280 (246-306) to 124 (60-200) at 4 weeks to 45 (34-76) at 12 weeks and further to 32 (20-50) at the end of 24 weeks. Simultaneously, a significant (P < 0.001) improvement in the mean hemoglobin and serum ferritin levels and a significant (P < 0.001) decrease in endometrial thickness were observed. The most common side effect was spotting (50.0%) and vaginal discharge (38.1%). LNG-IUS causes a remarkable reduction in menstrual blood loss and marked improvement in dysmenorrhea. It also reduces anemia by improving the hemoglobin and ferritin levels. Thus, it can serve as an effective treatment option for heavy menstrual bleeding in perimenopausal women and prevent the need for a hysterectomy.

Case report on treatment of Karuppai Naarthasai Kattigal (uterine fibroids) with Rasagandhi Mezhugu

Karuppai Naarthasai Kattigal (uterine fibroids) are benign tumors arising from the smooth muscles of the uterus. This study focuses over a case report of a patient with Karuppai Naarthasai Kattigal (uterine fibroids) treated with a classical Siddha drug, Rasagandhi Mezhugu (RGM) from the literature reference Pulippani Vaithiyam-500, for a period of 90 days, after receiving the informed consent, and the outcome was documented. A 40-year-old woman with a heavy menstrual bleeding, frequent urination, abdominal cramps, and bloating of abdomen often for 6 months and intermenstrual bleeding for 2 years was screened through an ultrasonogram, suspecting uterine fibroids. After Siddha clinical assessment and diagnosis, RGM was administered for a period of 90 days with 15 days drug holiday after 45 days of treatment. Later the treatment outcomes were measured and the patient is followed up for 6 months. This study reveals the outcome of the treatment of Karuppai Naarthasai Kattigal with RGM and the prognosis of the patient is calculated with, symptomatic improvement, reduction in size of fibroid and changes in pictorial blood assessment chart score from baseline visit to final visit and reduction in clinical symptoms of the patient by using uterine fibroid quality-of-life questionnaire, and the data were recorded.

Fibroid vascularisation assessed with 3D Power Doppler as predictor for fibroid related symptoms and quality of life; a pilot study.

Uterine fibroids present differently, from well vascularised up to calcified, with some causing heavy menstrual bleeding (HMB). To investigate the association between fibroid vascularisation and HMB, other fibroid related symptoms and quality of life (QOL). A single centre pilot study was carried out in the Netherlands. Women with a maximum of two fibroids who chose expectant management were included. 3D sonography including power doppler was performed at baseline and at 3, 6 and 12 months follow up. Women were asked to complete the Pictorial Blood Assessment Chart (PBAC) and Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaires at every visit. Main outcome measure: The association between fibroid vascularisation and HMB. 53 women were included in the study. Baseline fibroid vascularisation, measured as vascular index (VI) is associated with PBAC score; a 1% higher VI at baseline leads to an 11 point increase in PBAC score over time (RC 10.99, p=0.05, 95% CI -0.15 - 22.12). After correction for the baseline variables ethnicity and fibroid type the association becomes stronger (P<0.05). Fibroid volume at baseline and HMB are also associated: a 1 cm3 larger fibroid leads to 0.6 points increase in PBAC score over time (RC 0.56, p=0.03, 95% CI 0.05 - 1.07). Conclusions: This study highlights that both fibroid vascularisation and fibroid volume may be associated with an increase in menstrual blood loss, other fibroid related symptoms and QOL over time. What is new? We used 3D power doppler to predict symptomatic fibroids.

Feasibility of a Smartphone Application (App) Pictorial Blood Assessment Chart (PBAC) As an Endpoint in a Von Willebrand Disease Trial

Background: von Willebrand disease (VWD) is a common inherited bleeding disorder characterized by mucosal bleeding. Among affected women, up to 80% have heavy menstrual bleeding, which causes serious medical and psychological morbidity associated with iron deficiency, including reduced physical functioning, anxiety, depression, and poor quality of life. Standard therapies such as hormonal agents and desmopressin are poorly tolerated, and thus the lack of effective therapies for menorrhagia remains a major unmet healthcare need in women with VWD. We designed a prospective, multicenter randomized clinical trial, Von Willebrand Disease Minimize Menorrhage (VWDMin) Trial to compare recombinant VWF (Vonvendi®) with the current recommended non-hormonal agent, tranexamic acid (Lysteda®) . To determine the practicality, usefulness, and satisfaction of a mobile Smartphone Application (App) to gather bleeding data for this clinical trial, we conducted a cross-over study in women with VWD.Methods: We piloted a Pictorial Blood Assessment Chart (PBAC) App in women with type I von Willebrand disease (VWD) between 18 and 45 years of age. Women were randomized to one menstrual cycle using the Sisterhood App (http://www.sisterhoodapp.com/), a free commercial app developed by the Hemophilia Federation of America (HFA), or to PBAC by paper form, then crossed-over to the alternate PBAC for the next cycle. Participants downloaded the App to their own mobile devices and created an account with a username, email address, and password. Per IRB requirements, subjects did not send data via their personal emails or through the App directly, and instead used a dedicated study email account on an institutional server to maintain security and confidentiality. Blood loss data were tracked during monthly cycles by PBAC, a validated assessment tool for menstrual blood loss. At the completion of the two cycles, subjects completed an online survey (www.surveymonkey.com/r/8K9FGMG) regarding their experience with the App, including simplicity, accuracy, feasibility, and usability, as compared with paper form.Results: Thirteen women were randomized to paper or App between August and December 2016. Of these, 5 completed two cycles and the post-study survey. Of the remaining women, 1 withdrew from the study due to pregnancy, 1 withdrew due to difficulties with the App, and 6 were lost to follow-up. Among those who completed the post-study survey, 3 preferred the App and 2 preferred the paper form. Generally, participants liked the convenience of the App and additional App features such as symptom trackers and reports that could be sent directly to their physicians. All subjects felt the App was more or equally accurate compared with paper form. However, some noted occasional problems with the App freezing, and several cited the difficulty of setting up and using a separate study email required for security to send App data as a major obstacle to completing the study.Discussion: Mobile phone apps are convenient, accessible, widely used by patients, and demonstrate potential usefulness as tools for collecting clinical data. Our pilot study shows the Sisterhood App may be more convenient, preferred by patients, and at least equally accurate to paper PBAC for recording blood loss data in women with VWD. However, significant patient attrition, which may be in part due to the difficulty of setting up and using a secure institutional email to transmit App data, limits the utility of our results. IRB standards for data collection protect the confidentiality of patient information, but in our study may have made participation prohibitively difficult. Alternative methods of transmitting app-based data are needed before the Sisterhood App can be feasibly used to collect data for clinical studies. DisclosuresRagni:A Anylam, Biomarin, Bioverativ, Shire: Honoraria; Alnylam, CSL Behring, BAYER, Biomarin, Biomarin, Bioverativ, Genetech/Roche, Pfizer, Shire, SPARK: Research Funding.

Screening hemostatic defects in Saudi University students with unexplained menorrhagia: a diagnosis, which could be missed.

Bleeding disorders are a common cause of unexplained menorrhagia in adolescents. However, there is lack of information provided on Arab girls. To estimate the prevalence of coagulation factor deficiencies and platelet dysfunction among Saudi university students with unexplained menorrhagia. In this cross sectional study, 463 adolescent girls surveyed for having heavy menses for further evaluation of underlying bleeding tendencies using screening standardized questionnaire. Only 109 girls out of the total 463 girls reported menorrhagia and were included in the evaluation. All girls with menorrhagia were evaluated by Pictorial blood assessment chart (PBAC) for precise evaluation of menstrual blood loss (PBAC score >100), had underwent pelvic ultrasonography and screening of hemostatic abnormalities (complete blood count, PFA-100, PT, aPTT, vWF:RCo, vWF:Ag, coagulation factors assay). On the basis of the score of PBAC more than 100, 25.6% (28/109) of adolescent women (age ranged: 17-25 years old) had confirmed menorrhagia. In 30.8% of them, an ultimate diagnosis of bleeding tendency or hemostatic abnormality was detected [five cases of probable von Willebrand disease (vWD) or low level of vWF:Ag and/or vWF:RCo, two cases of probable platelet dysfunction, and one case of factorV (FV) deficiency]. Anemia was found in 39.28% (11/28) of them; however, only 4 (36%) had received iron supplements. Our study demonstrated that hemostatic defects are not uncommon in Saudi adolescent women presenting with menorrhagia but mostly unrecognized and untreated. It is probably advisable to screen women with menorrhagia for these defects.