scholarly journals Prospective Evaluation of ISTH-BAT As a Predictor of Bleeding Disorder in Adolescent Girls with Heavy Menstrual Bleeding

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1402-1402
Author(s):  
Shilpa Jain ◽  
Ravi Sarode ◽  
Janna M. Journeycake ◽  
Ayesha Zia
Keyword(s):  
Diagnostic Accuracy ◽  
Adolescent Girls ◽  
Roc Analysis ◽  
Assessment Tools ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding ◽  
Study Cohort ◽  
Operating Characteristics ◽  
The Mean ◽  
Bleeding Score

Background. Heavy menstrual bleeding (HMB) is a frequent complaint in adolescence and is often multifactorial. Of the possible causes, anovulation is likely to be the most common reason but there is mounting evidence that bleeding disorders (BDs) are often an unidentified cause of HMB. Wide ranges of reported prevalence, difficulty in discerning normal from excessive menstrual bleeding and the semi-empiric use of hormonal therapy makes identifying BDs in adolescents challenging. Bleeding assessment tools (BATs) have been developed- primarily in the adults - to improve diagnostic accuracy, predict bleeding phenotype and describe symptoms. The International Society of Haemostasis and Thrombosis (ISTH) BAT was specifically designed to quantify bleeding symptoms that are pediatric specific. An ISTH-BAT score of > 3 for children is considered abnormal. The ISTH BAT has not yet been specifically tested in adolescents presenting with HMB. The objective of this study was to examine the diagnostic utility of ISTH-BAT bleeding score (BS) of > 3 as a predictor of BDs in adolescents with HMB. Methods. We prospectively analyzed clinical data on 70 adolescents without a known BD, referred for HMB, to the Adolescent, Gynecology and multidisciplinary Young Women's Blood Disorders Clinics at University of Texas Southwestern Medical Center from July 2014 to June 2016. This cohort is part of an ongoing prospective study investigating the incidence of BDs in adolescents with HMB (planned n=200). All subjects underwent a standardized comprehensive diagnostic approach, including the ISTH BAT to quantify bleeding symptoms accurately. The ISTH-BAT was applied by two trained investigators and any discrepancy in scores was settled by discussion. As per National Heart, Lung, and Blood Institute guidelines, VWF:Ag and/or VWF:RCo<30 IU/dL were labeled "definite von Willebrand disease (VWD)" while 30-50 IU/dL were labeled as "low VWF levels" which were grouped together to represent vWD. Receiver operating characteristics (ROC) of ISTH-BAT were determined to assess its value for predicting BD in our cohort. Results. The mean age of study participants was 14.4+1.8 years (range: 11-18 years). Twenty-eight out of 70 patients (40%) were found to have a BD; 8 met criteria for VWD, 12 had low VWF levels, 2 were hemophilia A carriers, 5 were diagnosed with inherited platelet dysfunction and 1 had inherited thrombocytopenia. The mean BS was higher in subjects with VWD (N=20) as compared to those without a BD (N=42) (4.5 +1.6, vs. 3.6+ 1.0, p= 0.02). At least one other bleeding symptom was present in 8 (40%) of the 20 girls with vWD. The most commonly reported bleeding symptoms were epistaxis (35%), oral (15%), cutaneous (10%) and post-surgical (5%). There was no difference in patterns of menstrual bleeding (anovulatory vs. ovulatory) between girls with and without a BD (55% ovulatory vs. 41% ovulatory, p-=0.28). ROC analysis of the ISTH-BAT bleeding scores showed that at a BS of > 3, the sensitivity of the ISTH BAT was 100% but specificity was only marginal at 2.4% with an accuracy of 41%, whereas at a BS of > 5, sensitivity, specificity and accuracy were 30%, 88.10% and 69%, respectively. ROC analysis showed area under the curve of 0.66 (CI: 0.52-0.80) indicating poor discrimination for the ISTH-BAT score in determining BD in girls with HMB. Conclusion. Our study is the first attempt to prospectively examine the applicability of using ISTH-BAT score as a screening tool to exclude the presence of BD in adolescent girls presenting with HMB. In this study cohort, ISTH-BAT bleeding score of > 3 demonstrated poor diagnostic accuracy in ruling out vWD. A score of > 5 had high specificity which can decrease false positive diagnosis and repetitive testing. Future data from the ongoing study will help understand how a combination of BATs and a laboratory testing algorithm can unravel hemostatic defects in adolescents with HMB. Disclosures Jain: Bayer: Membership on an entity's Board of Directors or advisory committees; Biogen: Speakers Bureau; Novo Nordisk: Honoraria. Sarode:CSL Behring: Consultancy, Honoraria. Journeycake:CSL: Consultancy; Biogen: Consultancy; Baxalta/Shire: Consultancy. Zia:NHLBI K23: Research Funding.

scholarly journals Single-Nucleotide Variation Spectrum of the Factor XI Gene in Women with Heavy Menstrual Bleeding

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4213-4213
Author(s):  
Sophie Wiewel-Verschueren ◽  
André B Mulder ◽  
Karina Meijer ◽  
René Mulder
Keyword(s):  
Heavy Chain ◽  
Light Chain ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding ◽  
Control Group ◽  
Single Nucleotide Variants ◽  
Factor Xi ◽  
Single Nucleotide ◽  
Hardy Weinberg Equilibrium ◽  
Bleeding Score

Abstract Introduction: In plasma, factor XI (FXI) circulates as a homodimeric precursor of a serine protease (FXIa), which plays an essential role in the contact activation of coagulation through the conversion of FIX to FIXa in a calcium-dependent manner. Each FXI monomer contains a heavy chain and a light chain that are joined together by disulphide bonds. The heavy chain contains all four apple domains and the light chain contains the serine protease domain. The fourth apple domain is necessary for dimerization. The gene for FXI is located on the long arm of chromosome 4 (4q35) and contains 15 exons and 14 introns. To date, more than 240 mutations have been reported (http://www.factorxi.org). The prevalence of FXI deficiency in Caucasians is reported as low, but might be underestimated. Women with low FXI levels (<70%) are prone to excessive bleeding during menstruation. However, bleeding manifestations are not well correlated with the plasma FXI levels and bleeding episodes can vary widely among patients with similar low FXI levels. In our previous study (Knol et al, AJOG, 2013), we found 4% FXI deficiency (< 70%) in unselected Dutch women with heavy menstrual bleeding (HMB). We also found that patients had significantly longer APTT compared to controls (26.5 vs 25.0 sec; p=0.001), despite higher levels of factor VIII. This turned out to be caused by lower median levels of FXI (100 vs 124 IU/dL; p<0.001). These lower levels of FXI and increased bleeding tendency could be caused by the presence of specific single-nucleotide variants in the FXI gene in women with HMB. To our knowledge, systemic analysis of FXI gene variants in women with HMB has not been reported. Aim: to determine the single-nucleotide variants of the FXI gene in women with heavy menstrual bleeding. Methods: the study was approved by the Institutional Review Board of the University Medical Center of Groningen. Informed consent was obtained from all patients. We included patients referred for heavy menstrual bleeding (PBAC-score >100). We measured the Tosetto bleeding score by questionnaire. FXI activity levels were determined by an one-stage clotting assay (Siemens, Marburg, Germany). Reference interval was 65-150%. Direct sequencing analysis of all 15 exons and flanking introns of the factor XI gene was performed to detect single-nucleotide variants. Results were compared with the HapMap and 1000 genome database using the Fisher exact probability test on a 2x3 contingency table. In addition, we tested each single-nucleotide variant for Hardy-Weinberg equilibrium. Results: We included 49 patients. Median FXI level was 96% (range 61%-155%). We found 31 different single-nucleotide variants in 49 patients with HMB. Seven out of 31 could not be compared to the control group due to small numbers, unknown frequency, or absence from the database. From the remaining 24 single-nucleotide variants (Figure 1), two (rs925451 and rs2241817) showed a significant difference compared to the control group (P<0.01). These two single-nucleotide variants showed also a significant departure from the Hardy-Weinberg equilibrium (P<0.01). There was no correlation between the number of single-nucleotide variants and the FXI level, PBAC-score or bleeding score. Conclusions: Our study provides a detailed analysis of single-nucleotide variants of the factor XI gene. Among these 31 variants, rs925451 and rs2241817 seem to be associated with heavy menstrual bleeding.Overall, these data may serve as reference group for future studies on the molecular background of factor XI deficiency and heavy menstrual bleeding. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Single Brain Metastasis vs Glioblastoma Multiforme: A Voi-Based Multiparametric Analysys for Differential Diagnosis

2021 ◽  
Author(s):  
Andrea Romano ◽  
Giulia Moltoni ◽  
Alessia Guarnera ◽  
Luca Pasquini ◽  
Alberto Di Napoli ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Roc Analysis ◽  
Area Under The Curve ◽  
Solid Component ◽  
Signal Recovery ◽  
Operating Characteristics ◽  
Cerebral Lesions ◽  
Perilesional Edema ◽  
Volume Of Interest ◽  
The Mean

Abstract PURPOSEThe authors purpose was to evaluate ADC and rCBV values in the enhanced lesion, in the peritumoral area and in distal oedema using a Volume of Interest (VOI) based method and to analysed hemodynamic curves obtained from DSC perfusion MRI, in order to create a valid multiparametric MRI model for the differential diagnosis between Glioblastoma and solitary Brain Metastasis.MATERIALS AND METHODSForty-one patients (twenty glioblastomas and twenty-one single brain metastases) were retrospectively evaluated. MRI images were acquired before surgery, radiotherapy and chemotherapy. MRIs were analysed with Olea Sphere® 3.0 (Olea Medical, La Ciotat, France), in particular with diffusion, perfusion and volume of interest segmentation plug-ins. FLAIR, 3D T1 MP-RAGE images after gadolinium, ADC and rCBV maps for each patient were co-registered by the OleaSphere software; this was followed by visual inspection to ensure adequate alignment. Volumes of interest (VOIs) of the lesions were drawn on enhanced 3D T1 MP-RAGE avoiding cyst or necrotic degeneration, and then projected on ADC and rCBV co-registered maps. Another 2 VOIs were drawn in the region of hyperintense cerebral oedema, surrounding the lesion (GB or BM) visible on FLAIR images. The first VOI was drawn into perilesional oedema within 5mm around the enhancing tumor. The second VOI was drawn into residual oedema. Both VOIs were projected on ADC and rCBV maps. Perfusion curves were obtained for each lesion and the value of signal recovery (SR) was reported. A Two sample T-Test was obtained to compare all parameters of GB and BM groups. Receiver operating characteristics (ROC) analysis was performed to determine the optimal parameter in distinguishing GB from BM. RESULTSComparing all parameters evaluated for patients with GB and BM, the cerebral lesions were distinguishable with the mean ADC VOI- values of solid component, the PSR values and the mean and max rCBV values in the perilesional edema within 5mm around the enhancing tumor. According to ROC analysis, the area under the curve was 88%, 78% and 74% respectively for mean ADC VOI-values of the solid component, the mean and max rCBV values in the perilesional edema and the PSR. The cumulative ROC curve of these parameters reached an area under the curve of 95% .Using perilesional max rCBV>1,37, PSR>75% and mean lesional ADC<1x10-3 mm2 s-1 GB could be differentiated from solitary BM with sensitivity and specificity of 95% and 86%. CONCLUSIONWe can conclude that lower values of ADC in the enhancing tumor volume and a higher percentage of signal recovery in perfusion curves, associated with higher values of rCBV in the peritumoral edema closed to the lesion, are strongly indicative of GB than solitary BM.

Exploring the Unmet Needs of Parents of Adolescent Girls with Heavy Menstrual Bleeding and Dysmenorrhea: A Qualitative Study

2020 ◽  
Vol 33 (3) ◽  
pp. 271-277 ◽  
Author(s):  
Emily K. Bellis ◽  
Anna D. Li ◽  
Yasmin L. Jayasinghe ◽  
Jane E. Girling ◽  
Sonia R. Grover ◽  
...  
Keyword(s):  
Qualitative Study ◽  
Adolescent Girls ◽  
Unmet Needs ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding

Heavy Menstrual Bleeding in Adolescent Girls

2020 ◽  
Vol 49 (4) ◽  
pp. e163-e169
Author(s):  
Jennifer Davila ◽  
Elizabeth M. Alderman
Keyword(s):  
Adolescent Girls ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding

Hematologic Considerations and Management of Adolescent Girls with Heavy Menstrual Bleeding and Anemia in US Children's Hospitals

2018 ◽  
Vol 31 (5) ◽  
pp. 446-450 ◽  
Author(s):  
Jacquelyn M. Powers ◽  
Joseph R. Stanek ◽  
Lakshmi Srivaths ◽  
Fareeda W. Haamid ◽  
Sarah H. O'Brien
Keyword(s):  
Adolescent Girls ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding ◽  
Children's Hospitals ◽  
Children’S Hospitals

Unmet Needs and Experiences of Adolescent Girls with Heavy Menstrual Bleeding and Dysmenorrhea: A Qualitative Study

2020 ◽  
Vol 33 (3) ◽  
pp. 278-284 ◽  
Author(s):  
Anna D. Li ◽  
Emily K. Bellis ◽  
Jane E. Girling ◽  
Yasmin L. Jayasinghe ◽  
Sonia R. Grover ◽  
...  
Keyword(s):  
Qualitative Study ◽  
Adolescent Girls ◽  
Unmet Needs ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding

scholarly journals Comprehensive Evaluation of Bleeding Disorders in Adolescents with Heavy Menstrual Bleeding

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 876-876
Author(s):  
Ayesha Zia ◽  
Janna M. Journeycake ◽  
Shilpa Jain ◽  
Ravi Sarode
Keyword(s):  
Comprehensive Evaluation ◽  
Von Willebrand Disease ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding ◽  
Laboratory Evaluation ◽  
Age At Menarche ◽  
Thrombin Time ◽  
Hypermobility Syndrome ◽  
Patient Reported ◽  
The Mean

Introduction: Unpredictable, prolonged or heavy menstrual bleeding (HMB) is not unusual in many adolescents soon after menarche. Anovulation, owing to immaturity of the hypothalamic-pituitary-ovarian axis, is often the cause of HMB; however, it may coexist and mask an underlying bleeding disorder (BD). Retrospective data in adolescents with HMB suggest a prevalence of BDs from 10 to 62%. Prospective studies with uniform hemostatic evaluation and concurrent quality of life (QoL) assessments have not been performed. The incidence of BDs in adolescents, especially those with anovulatory bleeding, remains unknown. Methods: In this ongoing prospective cohort study (targeted n=200), 130 adolescents referred for HMB to multidisciplinary Young Women's Blood Disorders Clinics were enrolled. An assessment of menstrual loss using pictorial blood assessment chart (PBAC) and bleeding symptoms using ISTH-bleeding assessment tool (BAT) was undertaken. Participants underwent a comprehensive evaluation determined a priori, including assessment of hypermobility, standardized laboratory evaluation (prothrombin time, activated partial thromboplastin time, fibrinogen, thrombin time, von Willebrand disease (VWD) panel, whole blood platelet aggregation with ATP secretion, factor assays (FIX and FXIII), global hemostasis and hyperfibrinolysis using ROTEM, and a pelvic ultrasound (US). Patient reported outcomes for health related QoL(HR-QoL) was completed. Results: The mean age of participants was 14 (range 11-18) and mean age at menarche was 11.7 yrs. (range: 9-16). The mean PBAC score, before contraceptive initiation, was 504 (range: 100- 1200) and the mean ISTH BAT score was 3.8 (range: 1-8) in all participants. 62% had anovulatory menstrual bleeding. An inherited BD and/or bleeding risk was diagnosed in 24.6% (n=32); 9% (n=12) were diagnosed with VWD, 5% (n=6) with qualitative platelet dysfunction and 2 subjects were found to be hemophilia A (HA) carriers. Low VWF levels (VWF:Rco 30-50%) were detected in 9% (n=12). 15% had evidence of mild systemic hyperfibrinolysis (lysis 3-8% on ROTEM) but none met the criteria for further investigation for an inherited disorder of hyperfibrinolysis . Of those without BD, 2 were diagnosed to have VWF exon 28 polymorphism, and 3 were referred and ultimately diagnosed with hypermobility syndrome by Genetics. One was found to have endometriosis by laparoscopy and 3 were diagnosed with PCOS. Of those with BDs (all with low VWF), 3 were diagnosed with hypermobility syndrome (total 6) and 4 with PCOS (total 7). US was normal in all subjects. The PBAC scores were higher in BDs (634 vs. 410; SD ± 275 p=0.002), irrespective of the pattern of bleeding. No differences were found in the ISTH BAT scores (after excluding HA carriers) (3.6 vs. 4.8; SD ± 1.19, p=0.06), initial hbg or ferritin levels between the two groups. Only 6% (n=8) with BDs required ED visit and/or hospitalization for HMB vs. 14% (n=18) without a BD, of which majority had anovulatory bleeding. On multivariate logistic regression, no predictors of BDs were found. Adolescents with BDs had a decreased HR-QoL compared to those without a BD (QoL score 58 vs.87; SD± 12.5, p=<0.001) even after control of HMB and correction of anemia. Conclusions: Inherited BDs are common in adolescents with HMB, confer a decreased HR-QoL and can be associated with anovulatory bleeding. A comprehensive evaluation is required to unravel disorders causing HMB. In this ongoing study, at this time, no predictor of an inherited BD was found in adolescents with HMB. Data accrual from the fully powered, ongoing, prospective study may offer further data to develop an ideal tool with a scoring system to take into account all prevalent causes of HMB to accurately predict a BD in adolescents. Disclosures Zia: NHLBI K23: Research Funding. Journeycake:CSL: Consultancy; Biogen: Consultancy; Baxalta/Shire: Consultancy. Jain:Novo Nordisk: Honoraria; Bayer: Membership on an entity's Board of Directors or advisory committees; Biogen: Speakers Bureau. Sarode:CSL Behring: Consultancy, Honoraria.

scholarly journals Study of menstrual disorder in adolescent girls at tertiary care centre in rural area

2018 ◽  
Vol 7 (5) ◽  
pp. 1979
Author(s):  
Anubhuti Yadav ◽  
Deepa L. Masand
Keyword(s):  
Rural Area ◽  
Adolescent Girls ◽  
Total Population ◽  
Tertiary Care ◽  
Adolescent Females ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding ◽  
World Population ◽  
Menstrual Hygiene ◽  
Tract Infections

Background: Total adolescent world population is 16%.  Adolescents (10-19 years) constitute 21.3% i.e. nearly 1/5th of total population of India. 19% of the total population-faces a series of serious challenges not only affecting their growth and development but also their livelihood as adults. The objective of the current study was to observe the menstrual disorders among adolescent females and to observe the demographic profile and assess hygiene practices during menstruation and grade of anemia due to menstrual morbidity.  Methods: A random selection of adolescent’s females were done from gynaecology outpatient department at a tertiary care hospital in rural area. Study done on 180 adolescent girls from January 01, 2016 to June 31st, 2017, it is a descriptive type of observational study. Counseling done of adolescent females on menstrual hygiene and nutrition. Results: Most common menstrual morbidity seen in this study is dysmenorrhea (41.66%) followed by heavy menstrual bleeding i.e 25% and irregular menstrual bleeding (13.33%) subsequently. All these problems are associated with their practices used during menstruation. Poor menstrual hygiene was seen associated with 30 to 35% of abdominal cramps and mood swings, heavy menstrual bleeding and nutritional deficiency leads to moderate anemia (7 to10 gm%) in 83%.Conclusions: Due to unhygienic practices and lack of education and awareness about hygiene many of the girls were suffering from reproductive tract infections and poor nutrition leads to anemia. So, we all need to educate them about hygiene and spread awareness about the various services provided by the government like supplying of sanitary napkins to overcome infections.

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