{"title":"Successful Orthopaedic Surgeries With World Federation of Haemophilia Humanitarian Aid Program in Resource-Limited Settings","authors":"Rema Ganapathi, Neeraj Sidharthan, Jecko Thachil","doi":"10.1111/hae.15141","DOIUrl":"10.1111/hae.15141","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 1","pages":"162-165"},"PeriodicalIF":3.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shrimati Shetty, Cecil Ross, M. Joseph John, Shrinath Kshirsagar, Nimish Kulkarni, D. S. Pavitra, Diksha Sarwan, P. K. Misha, Antony Paul, Apurva More, Nazish Kaunchale, Magdalene D'silva, Shrushti Masurkar, Shruti Kharat, Kranti Patil, Shalaka Patel, Priti Mehendale, Prachi Sarvaiya, Savita Rangarajan
Introduction
Mortality and morbidity in persons with haemophilia (PWH) have decreased due to improved diagnosis and treatment along with comprehensive population outreach efforts, but the impact is not uniform in different countries.
Aim
The study aims to assess all-cause and intracranial haemorrhage (ICH)-specific mortality of PWH in India.
Methods
This is a retrospective, observational, multi-centric cohort study of 1020 haemophilia patients from three centres in India. The mortality data in the family was collected from personal interviews, and subsequently confirmed with the corresponding haemophilia treatment centres (HTCs). The demographic and clinical data, along with other comorbidities, were collected from the medical records.
Results
Among 170 reported deaths, 73 (42.9%) were caused by ICH, and 44 (25.9%) resulted from accidents or trauma. Gastrointestinal (GI) bleeding was the third most common cause of death, accounting for 27 cases (15.9%). The average and median ages at death were 27.7 and 26 years, respectively. None of the deceased cases were receiving any prophylactic or immune tolerance induction (ITI) therapy, and all had severe haemophilia. In addition, the prevalence of inhibitors and hypertension was significantly higher in deceased cases compared to that in the general haemophilia population (p < 0.05).
Conclusion
Severity of haemophilia, episodic treatment, hypertension and inhibitors showed significant association with mortality. ICH continues to be the leading cause of death among haemophilia patients in the country. This underscores the challenges in managing haemophilia and the need for improved treatment strategies to increase the life expectancy of PWH.
{"title":"Mortality in Haemophilia Patients in India: A National Cohort Study","authors":"Shrimati Shetty, Cecil Ross, M. Joseph John, Shrinath Kshirsagar, Nimish Kulkarni, D. S. Pavitra, Diksha Sarwan, P. K. Misha, Antony Paul, Apurva More, Nazish Kaunchale, Magdalene D'silva, Shrushti Masurkar, Shruti Kharat, Kranti Patil, Shalaka Patel, Priti Mehendale, Prachi Sarvaiya, Savita Rangarajan","doi":"10.1111/hae.15143","DOIUrl":"10.1111/hae.15143","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Mortality and morbidity in persons with haemophilia (PWH) have decreased due to improved diagnosis and treatment along with comprehensive population outreach efforts, but the impact is not uniform in different countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The study aims to assess all-cause and intracranial haemorrhage (ICH)-specific mortality of PWH in India.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a retrospective, observational, multi-centric cohort study of 1020 haemophilia patients from three centres in India. The mortality data in the family was collected from personal interviews, and subsequently confirmed with the corresponding haemophilia treatment centres (HTCs). The demographic and clinical data, along with other comorbidities, were collected from the medical records.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 170 reported deaths, 73 (42.9%) were caused by ICH, and 44 (25.9%) resulted from accidents or trauma. Gastrointestinal (GI) bleeding was the third most common cause of death, accounting for 27 cases (15.9%). The average and median ages at death were 27.7 and 26 years, respectively. None of the deceased cases were receiving any prophylactic or immune tolerance induction (ITI) therapy, and all had severe haemophilia. In addition, the prevalence of inhibitors and hypertension was significantly higher in deceased cases compared to that in the general haemophilia population (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Severity of haemophilia, episodic treatment, hypertension and inhibitors showed significant association with mortality. ICH continues to be the leading cause of death among haemophilia patients in the country. This underscores the challenges in managing haemophilia and the need for improved treatment strategies to increase the life expectancy of PWH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 1","pages":"132-139"},"PeriodicalIF":3.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chelsea Howie, Hannah Cameron, Mandy Bouchard, Victoria Price, Nancy L. Young, Meghan Pike
Aim
Heavy menstrual bleeding (HMB) affects up to 37% of adolescents. Given the paucity of available tools to assess health-related quality of life (HRQoL) in adolescents with HMB, we developed the adolescent menstrual bleeding questionnaire (aMBQ), a valid and reliable measure of bleeding-related quality of life. The aim of this study was cross-cultural translation and adaptation of the English aMBQ into French to ensure accessibility for more Canadian adolescents who menstruate.
Methods
A five-step process was followed: (1) forward translation from English to Canadian French; (2) backward translation from French to English; (3) review of source and translated aMBQ to create a reconciled version; (4) cognitive debriefing to ensure linguistic and clinical equivalence and (5) review of cognitive debriefings to produce the final version of the French aMBQ. Results of cognitive debriefings were reviewed after every three participants; items were revised if presented as an issue by ≥2 participants. These changes were implemented and tested in cognitive debriefings until saturation was reached.
Results
Linguistic changes were made to nine (33%) of the questions and one (3.7%) answer options. Major changes were made to four of the 27 questions (15%), and minor changes were made to five of the 27 questions (19%).
Conclusion
Professional translators, clinical experts and patient input through cognitive debriefing are pivotal to successful cross-cultural translation. Results of cognitive debriefing interviews suggest the French aMBQ is easily understood and confirms its face validity.
{"title":"Cross-Cultural Translation of the Adolescent Menstrual Bleeding Questionnaire (AMBQ)","authors":"Chelsea Howie, Hannah Cameron, Mandy Bouchard, Victoria Price, Nancy L. Young, Meghan Pike","doi":"10.1111/hae.15145","DOIUrl":"10.1111/hae.15145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Heavy menstrual bleeding (HMB) affects up to 37% of adolescents. Given the paucity of available tools to assess health-related quality of life (HRQoL) in adolescents with HMB, we developed the adolescent menstrual bleeding questionnaire (aMBQ), a valid and reliable measure of bleeding-related quality of life. The aim of this study was cross-cultural translation and adaptation of the English aMBQ into French to ensure accessibility for more Canadian adolescents who menstruate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A five-step process was followed: (1) forward translation from English to Canadian French; (2) backward translation from French to English; (3) review of source and translated aMBQ to create a reconciled version; (4) cognitive debriefing to ensure linguistic and clinical equivalence and (5) review of cognitive debriefings to produce the final version of the French aMBQ. Results of cognitive debriefings were reviewed after every three participants; items were revised if presented as an issue by ≥2 participants. These changes were implemented and tested in cognitive debriefings until saturation was reached.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Linguistic changes were made to nine (33%) of the questions and one (3.7%) answer options. Major changes were made to four of the 27 questions (15%), and minor changes were made to five of the 27 questions (19%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Professional translators, clinical experts and patient input through cognitive debriefing are pivotal to successful cross-cultural translation. Results of cognitive debriefing interviews suggest the French aMBQ is easily understood and confirms its face validity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 1","pages":"118-121"},"PeriodicalIF":3.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Callie Berkowitz, Kristy Lee, Kristi Kirkland, Brenda Nielsen, Patrick Ellsworth, Alice Ma, Nigel S. Key
{"title":"Research Letter: Patient Attitudes Towards Haemophilia Gene Therapy at a US Haemophilia Treatment Center","authors":"Callie Berkowitz, Kristy Lee, Kristi Kirkland, Brenda Nielsen, Patrick Ellsworth, Alice Ma, Nigel S. Key","doi":"10.1111/hae.15139","DOIUrl":"10.1111/hae.15139","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 1","pages":"166-168"},"PeriodicalIF":3.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Chapin, Maria Teresa Álvarez Román, Mila Ayash-Rashkovsky, Dorothee Diogo, Jon Kenniston, Francisco-Jose Lopez-Jaime, Caterina Maggiore, María-Eva Mingot-Castellano, Kavitha Rajavel, Antoine Rauch, Sophie Susen, Marcin von Grotthuss, Matt Wagoner, Qin Wang
Introduction
Haemophilia A is an X-linked bleeding disorder resulting from a deficiency of factor VIII (FVIII). To date, multiple gene therapies have entered clinical trials with the goal of providing durable haemostatic protection from a single dose. TAK 754 (BAX 888) is an investigational AAV8-based gene therapy containing a FVIII transgene. Reduction in CpG motifs was performed to reduce immunogenicity based on prior observations. Here, we describe the results of the first two cohorts treated with TAK 754.
Aim
To report clinical and translational results of the TAK-754 phase 1/2 AAV gene therapy study for the treatment of haemophilia A.
Methods
A phase 1/2 single arm open-label dose escalation study of TAK-754 was performed in participants with severe haemophilia A (NCT03370172). Participants were monitored for safety events, endogenous FVIII activity and bleeding rates. Glucocorticoids were implemented to preserve transgene expression. A transcriptomics analysis was performed to evaluate immunogenicity along with additional post-hoc analyses.
Results
Four participants were dosed in two cohorts. Infusion of TAK 754 was well-tolerated. All participants developed mild transient transaminase elevation and subsequent loss of FVIII expression within the first 12 months of treatment despite use of glucocorticoids. Transcriptomic analysis did not demonstrate significant changes in immunogenicity signals in peripheral blood. One serious adverse event of hypophosphatemia occurred in the second cohort without obvious risk factors.
Conclusions
Sustained FVIII expression remains a challenge in haemophilia A AAV gene therapy trials. Mechanisms of transgene expression loss require further study as clinical studies enter long term follow-up periods.
{"title":"A phase 1/2 safety and efficacy study of TAK-754 gene therapy: The challenge of achieving durable factor VIII expression in haemophilia A clinical trials","authors":"John Chapin, Maria Teresa Álvarez Román, Mila Ayash-Rashkovsky, Dorothee Diogo, Jon Kenniston, Francisco-Jose Lopez-Jaime, Caterina Maggiore, María-Eva Mingot-Castellano, Kavitha Rajavel, Antoine Rauch, Sophie Susen, Marcin von Grotthuss, Matt Wagoner, Qin Wang","doi":"10.1111/hae.15121","DOIUrl":"10.1111/hae.15121","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Haemophilia A is an X-linked bleeding disorder resulting from a deficiency of factor VIII (FVIII). To date, multiple gene therapies have entered clinical trials with the goal of providing durable haemostatic protection from a single dose. TAK 754 (BAX 888) is an investigational AAV8-based gene therapy containing a FVIII transgene. Reduction in CpG motifs was performed to reduce immunogenicity based on prior observations. Here, we describe the results of the first two cohorts treated with TAK 754.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To report clinical and translational results of the TAK-754 phase 1/2 AAV gene therapy study for the treatment of haemophilia A.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A phase 1/2 single arm open-label dose escalation study of TAK-754 was performed in participants with severe haemophilia A (NCT03370172). Participants were monitored for safety events, endogenous FVIII activity and bleeding rates. Glucocorticoids were implemented to preserve transgene expression. A transcriptomics analysis was performed to evaluate immunogenicity along with additional post-hoc analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four participants were dosed in two cohorts. Infusion of TAK 754 was well-tolerated. All participants developed mild transient transaminase elevation and subsequent loss of FVIII expression within the first 12 months of treatment despite use of glucocorticoids. Transcriptomic analysis did not demonstrate significant changes in immunogenicity signals in peripheral blood. One serious adverse event of hypophosphatemia occurred in the second cohort without obvious risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sustained FVIII expression remains a challenge in haemophilia A AAV gene therapy trials. Mechanisms of transgene expression loss require further study as clinical studies enter long term follow-up periods.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 1","pages":"108-117"},"PeriodicalIF":3.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physical therapy benefits patients with haemophilia (PWH), but its impact on the health-related quality of life (HRQOL) remains unclear.
Aim
This systematic review and meta-analysis investigated the association of physical therapy, including therapeutic exercise, manual therapy, and physical agent modality, with HRQOL improvement in PWH.
Methods
Databases PubMed, Embase, MEDLINE, and Scopus were searched from inception until April 2024. This review included randomised controlled trials (RCTs) that compare the HRQOL between the physical therapy and control groups. Relevant data and outcome values of included study were collected. Cochrane collaboration's tool and the grading of recommendations, assessment, development, and evaluation approach were used for risk of bias (ROB) and evidence-level assessment, individually.
Results
The systematic review included eight RCTs that involved 298 male PWH. The meta-analysis for HRQOL improvement revealed a significant difference in favour of physical therapy (standardised mean difference [SMD] = .92; 95% confidence interval [CI]:.50–1.33; p < .001). Therapeutic exercise exhibited more benefits in HRQOL improvement than the control groups (SMD = 1.02; 95% CI:.49–1.55; p < .001). Physical therapy effectively improved HRQOL in PWH with better joint status (SMD = 1.74; 95% CI:.97–2.51; p < .001). Of the eight RCTs, six were rated as high ROB. The comparisons revealed a moderate certainty of evidence.
Conclusions
Physical therapy, especially therapeutic exercise, effectively improved the HRQOL of PWH. Maintaining better joint status and timely physical therapy intervention is crucial for HRQOL improvements in PWH. Cautious interpretation is required due to evidence limitations.
{"title":"Effects of physical therapy on health-related quality of life in patients with haemophilia: A systematic review and meta-analysis","authors":"Chien-Min Chen, Shang-Lin Liu, Mu-Ching Shie","doi":"10.1111/hae.15120","DOIUrl":"10.1111/hae.15120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Physical therapy benefits patients with haemophilia (PWH), but its impact on the health-related quality of life (HRQOL) remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This systematic review and meta-analysis investigated the association of physical therapy, including therapeutic exercise, manual therapy, and physical agent modality, with HRQOL improvement in PWH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Databases PubMed, Embase, MEDLINE, and Scopus were searched from inception until April 2024. This review included randomised controlled trials (RCTs) that compare the HRQOL between the physical therapy and control groups. Relevant data and outcome values of included study were collected. Cochrane collaboration's tool and the grading of recommendations, assessment, development, and evaluation approach were used for risk of bias (ROB) and evidence-level assessment, individually.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The systematic review included eight RCTs that involved 298 male PWH. The meta-analysis for HRQOL improvement revealed a significant difference in favour of physical therapy (standardised mean difference [SMD] = .92; 95% confidence interval [CI]:.50–1.33; <i>p</i> < .001). Therapeutic exercise exhibited more benefits in HRQOL improvement than the control groups (SMD = 1.02; 95% CI:.49–1.55; <i>p</i> < .001). Physical therapy effectively improved HRQOL in PWH with better joint status (SMD = 1.74; 95% CI:.97–2.51; <i>p</i> < .001). Of the eight RCTs, six were rated as high ROB. The comparisons revealed a moderate certainty of evidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Physical therapy, especially therapeutic exercise, effectively improved the HRQOL of PWH. Maintaining better joint status and timely physical therapy intervention is crucial for HRQOL improvements in PWH. Cautious interpretation is required due to evidence limitations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 1","pages":"16-25"},"PeriodicalIF":3.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Behnaz Pezeshkpoor, Ronald Fischer, Barbara Preisler, Katrin Hartlieb, Heiko Rühl, Jens Müller, Silvia Horneff, Natascha Marquardt, Anna Pavlova, Johannes Oldenburg
Introduction
Maintaining the balance between procoagulant and anticoagulant factors is essential for effective haemostasis. Emerging evidence suggests a modulation of bleeding tendency by factors in the anticoagulant and fibrinolytic systems.
Aim
This study investigates the clinical and laboratory characteristics of a family with combined von Willebrand disease (VWD) and antithrombin (AT) deficiency.
Methods
The study focused on a 38-year-old female index patient (IP) with severe type 3 VWD and a history of bleeding disorders. Coagulation assays included VWF antigen, platelet-dependent VWF activity, factor VIII activity, thrombin generation assay (TGA) and AT activity. Molecular genetic analyses were conducted by a targeted DNA custom next generation sequencing (NGS) panel.
Results
The IP and one of her sisters suffered type 3 VWD. While the IP presents with a classical severe bleeding phenotype, the sister (II-2) exhibited less severe bleeding symptoms. Extended family members showed type 1 VWD with mild presentations. NGS revealed a homozygous deletion of exon 6 in the VWF gene in the IP and her sister (II-2). All other family members carry this genetic variant in a heterozygous state. Additionally, II-2 has a heterozygous variant in the SERPINC1 gene (c.133C>T, p.Arg45Trp). Both IP and II-2 carry a homozygous prothrombin G20210A variant. TGA results indicated reduced thrombin generation in severe VWD patients, with a pronounced thrombin burst in those with the AT and prothrombin G20210A variant.
Conclusions
AT deficiency appears to modulate bleeding symptoms in severe VWD. This study emphasizes the importance of comprehensive genetic and phenotypic evaluation in managing complex coagulation disorders.
{"title":"Modulation of Haemostatic Balance in Combined von Willebrand Disease and Antithrombin Deficiency: A Comprehensive Family Study","authors":"Behnaz Pezeshkpoor, Ronald Fischer, Barbara Preisler, Katrin Hartlieb, Heiko Rühl, Jens Müller, Silvia Horneff, Natascha Marquardt, Anna Pavlova, Johannes Oldenburg","doi":"10.1111/hae.15147","DOIUrl":"10.1111/hae.15147","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Maintaining the balance between procoagulant and anticoagulant factors is essential for effective haemostasis. Emerging evidence suggests a modulation of bleeding tendency by factors in the anticoagulant and fibrinolytic systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study investigates the clinical and laboratory characteristics of a family with combined von Willebrand disease (VWD) and antithrombin (AT) deficiency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study focused on a 38-year-old female index patient (IP) with severe type 3 VWD and a history of bleeding disorders. Coagulation assays included VWF antigen, platelet-dependent VWF activity, factor VIII activity, thrombin generation assay (TGA) and AT activity. Molecular genetic analyses were conducted by a targeted DNA custom next generation sequencing (NGS) panel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The IP and one of her sisters suffered type 3 VWD. While the IP presents with a classical severe bleeding phenotype, the sister (II-2) exhibited less severe bleeding symptoms. Extended family members showed type 1 VWD with mild presentations. NGS revealed a homozygous deletion of exon 6 in the <i>VWF</i> gene in the IP and her sister (II-2). All other family members carry this genetic variant in a heterozygous state. Additionally, II-2 has a heterozygous variant in the <i>SERPINC1</i> gene (c.133C>T, p.Arg45Trp). Both IP and II-2 carry a homozygous prothrombin G20210A variant. TGA results indicated reduced thrombin generation in severe VWD patients, with a pronounced thrombin burst in those with the AT and prothrombin G20210A variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AT deficiency appears to modulate bleeding symptoms in severe VWD. This study emphasizes the importance of comprehensive genetic and phenotypic evaluation in managing complex coagulation disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 1","pages":"140-147"},"PeriodicalIF":3.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ciro Miele, Francesca D'Auria, Luca Manfredi, Paolo Conca, Ernesto Cimino, Rosaria Mormile, Sabrina De Simone, Olga Scudiero, Marcella Savoia, Antonella Tufano, Matteo Nicola Dario Di Minno, Filomena Capasso, Cristina Mazzaccara
{"title":"Pharmacokinetic Studies, Assessing the Efficiency of FVIII/VWF Concentrates and Intravenous Human Immunoglobulin, Revealed the Etiopathogenesis of Acquired von Willebrand Disease in Patient With MGUS.","authors":"Ciro Miele, Francesca D'Auria, Luca Manfredi, Paolo Conca, Ernesto Cimino, Rosaria Mormile, Sabrina De Simone, Olga Scudiero, Marcella Savoia, Antonella Tufano, Matteo Nicola Dario Di Minno, Filomena Capasso, Cristina Mazzaccara","doi":"10.1111/hae.15137","DOIUrl":"https://doi.org/10.1111/hae.15137","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>It is interesting to reflect on the history of the journal <i>Haemophilia</i> on the completion of 30 years of publication.</p><p>The launch issue, <i>Haemophilia</i> (1995)1, 74–76, ‘<i>Dedicated to the exchange of information concerning the comprehensive care of haemophilia</i>’, was published by <i>Blackwell Science</i> and appeared in October 1994.</p><p>In 1939, Blackwell Scientific Publications (BSP), under the chairmanship of Mr Basil Blackwell, seized the opportunity to publish ‘medical and scientific research books’ when the generosity of William Morris, later Lord Nuffield, who owned the thriving car industry Morris Motors, endowed Nuffield professorial chairs in Medicine, Anaesthesia and Orthopaedics in the Oxford University Clinical School. The face of medicine in Oxford changed dramatically and, with it, the assumption that medical books would be written in greater numbers. However, during the following World War years, the BSP remained largely dormant.</p><p>BSP has always held a prominent position in haematology publication and, in 1955, the very first journal it launched was the <i>British Journal of Haematology</i>. Gwyn Macfarlane, a pioneer in haemophilia care in Oxford, whose book co-authored with Rosemary Biggs was also published by BSP, was an enthusiastic supporter of this new move into scientific journal publication.</p><p>My inspiration to approach BSP in the early 1990s to publish <i>Haemophilia</i> was that the continuing expansion of literature relating to the comprehensive care of haemophilia was distributed amongst a variety of specialist journals, and it was sometimes difficult for health care professionals to keep up to date.</p><p>I thought it was important, from the outset, that <i>Haemophilia</i> should become the official journal of the World Federation of Hemophilia (WFH) in order that the State-of-the-Art lectures and the abstracts from the biannual meeting of the Federation could be published. Shelby Dietrich, publications officer for WFH, was very supportive of the proposal. BSP wanted a North American co-editor and Doreen Brettler of the New England Hemophilia Centre agreed to edit with me. Whilst we attended the World AIDS meeting in Berlin in spring 1992, together, we discussed plans for the journal including a potential editorial board: we wanted this to be both multi-disciplinary and international.</p><p>In 1992, the journal <i>Haemophilia</i> was adopted as the official journal of WFH during a meeting to discuss the WFH 1990 Decade Plan in Estoril, Portugal. At my request, BSP provided a ‘mock up’ silver front cover with red lettering and using the spelling ‘haemophilia’, which was accepted.</p><p>The contents of the launch issue in October 1994 contained the report, written by Jean Lusher of the fourth joint WHO/WFH meeting held in Geneva in March 1994. The participants were physicians and scientists from seven countries, including Australia, India, Italy, Russia, Sweden, the UK and the USA and th
{"title":"Thirty Years of the Journal Haemophilia","authors":"Christine A. Lee","doi":"10.1111/hae.15127","DOIUrl":"10.1111/hae.15127","url":null,"abstract":"<p>It is interesting to reflect on the history of the journal <i>Haemophilia</i> on the completion of 30 years of publication.</p><p>The launch issue, <i>Haemophilia</i> (1995)1, 74–76, ‘<i>Dedicated to the exchange of information concerning the comprehensive care of haemophilia</i>’, was published by <i>Blackwell Science</i> and appeared in October 1994.</p><p>In 1939, Blackwell Scientific Publications (BSP), under the chairmanship of Mr Basil Blackwell, seized the opportunity to publish ‘medical and scientific research books’ when the generosity of William Morris, later Lord Nuffield, who owned the thriving car industry Morris Motors, endowed Nuffield professorial chairs in Medicine, Anaesthesia and Orthopaedics in the Oxford University Clinical School. The face of medicine in Oxford changed dramatically and, with it, the assumption that medical books would be written in greater numbers. However, during the following World War years, the BSP remained largely dormant.</p><p>BSP has always held a prominent position in haematology publication and, in 1955, the very first journal it launched was the <i>British Journal of Haematology</i>. Gwyn Macfarlane, a pioneer in haemophilia care in Oxford, whose book co-authored with Rosemary Biggs was also published by BSP, was an enthusiastic supporter of this new move into scientific journal publication.</p><p>My inspiration to approach BSP in the early 1990s to publish <i>Haemophilia</i> was that the continuing expansion of literature relating to the comprehensive care of haemophilia was distributed amongst a variety of specialist journals, and it was sometimes difficult for health care professionals to keep up to date.</p><p>I thought it was important, from the outset, that <i>Haemophilia</i> should become the official journal of the World Federation of Hemophilia (WFH) in order that the State-of-the-Art lectures and the abstracts from the biannual meeting of the Federation could be published. Shelby Dietrich, publications officer for WFH, was very supportive of the proposal. BSP wanted a North American co-editor and Doreen Brettler of the New England Hemophilia Centre agreed to edit with me. Whilst we attended the World AIDS meeting in Berlin in spring 1992, together, we discussed plans for the journal including a potential editorial board: we wanted this to be both multi-disciplinary and international.</p><p>In 1992, the journal <i>Haemophilia</i> was adopted as the official journal of WFH during a meeting to discuss the WFH 1990 Decade Plan in Estoril, Portugal. At my request, BSP provided a ‘mock up’ silver front cover with red lettering and using the spelling ‘haemophilia’, which was accepted.</p><p>The contents of the launch issue in October 1994 contained the report, written by Jean Lusher of the fourth joint WHO/WFH meeting held in Geneva in March 1994. The participants were physicians and scientists from seven countries, including Australia, India, Italy, Russia, Sweden, the UK and the USA and th","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 6","pages":"1255"},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cedric Hermans, Mark W. Skinner, Brittany Gentile, Elise Lim, Miranda Minhas, Katya Moreno, Eunice Tzeng, Tyler W. Buckner
Introduction
People with haemophilia A (PwHA) experience acute and chronic pain associated with reduced quality of life (QoL).
Aims
This post hoc analysis of pooled data from the HAVEN 1 (NCT02622321), 3 (NCT02847637), 4 (NCT03020160) and STASEY (NCT0319179) studies assessed the impact of emicizumab prophylaxis on pain-related QoL in PwHA.
Methods
PwHA received emicizumab during the four studies. In this analysis, pain was assessed using patient-reported responses to pain-specific questions from the Haem-A-QoL/Haemo-QoL-SF and the pain/discomfort dimension of the EQ-5D-5L. Responses were recorded at baseline and at regular intervals for up to 78 weeks following treatment initiation. Additional analyses evaluated the population with target joints at baseline, and the overall population stratified by age, factor (F)VIII inhibitor status and prior treatment.
Results
At the data cut-off, 504 PwHA had been treated across the four studies; 464 and 470 completed the Haem-A-QoL/Haemo-QoL-SF and the EQ-5D-5L, respectively. Improvements in pain-related QoL were observed by Week 13 of emicizumab prophylaxis and maintained through Week 78. In the overall population, responses of ‘never/rarely’ for ‘my swellings hurt’ and ‘pain in joints’ increased from 37.0% and 30.0% at baseline to 84.0% and 61.0% by Week 13, suggesting reductions in acute and chronic pain, respectively. Similar improvements were seen in the target joint population, and across all strata. Greater improvements were observed in younger versus older PwHA.
Conclusion
Pain-related QoL improved with emicizumab prophylaxis regardless of target joints, age, FVIII inhibitor status or prior treatment. Haemophilia-specific assessments are needed to accurately capture and characterize pain in PwHA.
A型血友病（PwHA）患者的急性和慢性疼痛与生活质量（QoL）下降有关。目的：对HAVEN 1 （NCT02622321）、3 （NCT02847637）、4 （NCT03020160）和STASEY （NCT0319179）研究的汇总数据进行事后分析，评估emicizumab预防对PwHA患者疼痛相关生活质量的影响。方法：在四项研究中，PwHA患者接受了emicizumab治疗。在本分析中，通过患者报告对来自haema - qol /Haemo-QoL-SF和EQ-5D-5L的疼痛/不适维度的疼痛特异性问题的反应来评估疼痛。在治疗开始后的78周内，在基线和定期间隔记录反应。其他分析评估了基线时目标关节的人群，以及按年龄、因子(F)VIII抑制剂状态和既往治疗进行分层的总体人群。结果：在数据截止时，四项研究共治疗了504例PwHA；464和470分别完成了haema - qol /Haemo-QoL-SF和EQ-5D-5L。在emicizumab预防的第13周观察到疼痛相关生活质量的改善，并维持到第78周。在总体人群中，对于“我的肿胀疼痛”和“关节疼痛”回答“从不/很少”的比例从基线时的37.0%和30.0%上升到第13周时的84.0%和61.0%，表明急性和慢性疼痛分别有所减少。在目标关节群和所有阶层中都可以看到类似的改善。与老年PwHA相比，年轻PwHA的改善更大。结论：无论目标关节、年龄、FVIII抑制剂状态或既往治疗如何，emicizumab预防均可改善疼痛相关的生活质量。需要血友病特异性评估来准确捕获和表征PwHA的疼痛。
{"title":"Pain-Related Quality of Life Outcomes in People With Haemophilia A Receiving Emicizumab: A Post Hoc Analysis of the HAVEN 1, 3 and 4 and STASEY Studies","authors":"Cedric Hermans, Mark W. Skinner, Brittany Gentile, Elise Lim, Miranda Minhas, Katya Moreno, Eunice Tzeng, Tyler W. Buckner","doi":"10.1111/hae.15134","DOIUrl":"10.1111/hae.15134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>People with haemophilia A (PwHA) experience acute and chronic pain associated with reduced quality of life (QoL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This post hoc analysis of pooled data from the HAVEN 1 (NCT02622321), 3 (NCT02847637), 4 (NCT03020160) and STASEY (NCT0319179) studies assessed the impact of emicizumab prophylaxis on pain-related QoL in PwHA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PwHA received emicizumab during the four studies. In this analysis, pain was assessed using patient-reported responses to pain-specific questions from the Haem-A-QoL/Haemo-QoL-SF and the pain/discomfort dimension of the EQ-5D-5L. Responses were recorded at baseline and at regular intervals for up to 78 weeks following treatment initiation. Additional analyses evaluated the population with target joints at baseline, and the overall population stratified by age, factor (F)VIII inhibitor status and prior treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At the data cut-off, 504 PwHA had been treated across the four studies; 464 and 470 completed the Haem-A-QoL/Haemo-QoL-SF and the EQ-5D-5L, respectively. Improvements in pain-related QoL were observed by Week 13 of emicizumab prophylaxis and maintained through Week 78. In the overall population, responses of ‘never/rarely’ for ‘my swellings hurt’ and ‘pain in joints’ increased from 37.0% and 30.0% at baseline to 84.0% and 61.0% by Week 13, suggesting reductions in acute and chronic pain, respectively. Similar improvements were seen in the target joint population, and across all strata. Greater improvements were observed in younger versus older PwHA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pain-related QoL improved with emicizumab prophylaxis regardless of target joints, age, FVIII inhibitor status or prior treatment. Haemophilia-specific assessments are needed to accurately capture and characterize pain in PwHA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 1","pages":"87-98"},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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