Sofie Persson, Adam Fridhammar, Katarina Steen Carlsson, Erik Berntorp
{"title":"Recombinant FVIII replacement products for haemophilia A: An updated valuation by indirect comparison measuring area under the curve","authors":"Sofie Persson, Adam Fridhammar, Katarina Steen Carlsson, Erik Berntorp","doi":"10.1111/hae.15076","DOIUrl":"10.1111/hae.15076","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 5","pages":"1230-1233"},"PeriodicalIF":3.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563240","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}
Emily Symington, Savita Rangarajan, Will Lester, Bella Madan, Glenn F. Pierce, Priyanka Raheja, Carolyn Millar, Dane Osmond, Mingjin Li, Tara M. Robinson
Introduction
Valoctocogene roxaparvovec is an adeno-associated virus vector serotype 5 (AAV5)-mediated gene therapy approved for severe haemophilia A (HA).
Aim
To report the safety and efficacy of valoctocogene roxaparvovec 7 years after dosing in a phase 1/2 clinical study (NCT02576795).
Methods
Males ≥18 years with severe HA (factor VIII [FVIII] ≤1 international unit [IU]/dL) who were previously receiving exogenous FVIII and had no history of FVIII inhibitors or anti-AAV5 antibodies received valoctocogene roxaparvovec treatment and were followed for 7 (6 × 1013 vg/kg; n = 7) and 6 (4 × 1013 vg/kg; n = 6) years.
Results
In the last year, one participant in each cohort reported treatment-related adverse events (AEs): grade 1 (G1) hepatomegaly (6 × 1013), and G1 splenomegaly and G1 hepatic steatosis (4 × 1013). During all follow-up, mean annualized treated bleeds and exogenous FVIII infusion rates were ≥88% lower than baseline values. At years 7 and 6, mean (median) FVIII activity (chromogenic assay) was 16.2 (10.3) and 6.7 (7.2) IU/dL in the 6 × 1013 (n = 5) and 4 × 1013 (n = 4) cohorts, respectively, corresponding to mild haemophilia. Regression analyses of the last year estimated rate of change in FVIII activity was -0.001 and -0.07 IU/dL/week for the 6 × 1013 and 4 × 1013 cohorts, respectively. Two participants (6 × 1013) resumed prophylaxis in year 7: one after a non-treatment-related G4 serious AE of spontaneous internal carotid artery bleed, and the other to manage bleeds and FVIII activity.
Conclusions
The safety and efficacy of valoctocogene roxaparvovec remain generally consistent with previous reports, with good haemostatic control for most participants. Two participants returned to prophylaxis.
{"title":"Valoctocogene roxaparvovec gene therapy provides durable haemostatic control for up to 7 years for haemophilia A","authors":"Emily Symington, Savita Rangarajan, Will Lester, Bella Madan, Glenn F. Pierce, Priyanka Raheja, Carolyn Millar, Dane Osmond, Mingjin Li, Tara M. Robinson","doi":"10.1111/hae.15071","DOIUrl":"10.1111/hae.15071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Valoctocogene roxaparvovec is an adeno-associated virus vector serotype 5 (AAV5)-mediated gene therapy approved for severe haemophilia A (HA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To report the safety and efficacy of valoctocogene roxaparvovec 7 years after dosing in a phase 1/2 clinical study (NCT02576795).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Males ≥18 years with severe HA (factor VIII [FVIII] ≤1 international unit [IU]/dL) who were previously receiving exogenous FVIII and had no history of FVIII inhibitors or anti-AAV5 antibodies received valoctocogene roxaparvovec treatment and were followed for 7 (6 × 10<sup>13</sup> vg/kg; <i>n</i> = 7) and 6 (4 × 10<sup>13</sup> vg/kg; <i>n</i> = 6) years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the last year, one participant in each cohort reported treatment-related adverse events (AEs): grade 1 (G1) hepatomegaly (6 × 10<sup>13</sup>), and G1 splenomegaly and G1 hepatic steatosis (4 × 10<sup>13</sup>). During all follow-up, mean annualized treated bleeds and exogenous FVIII infusion rates were ≥88% lower than baseline values. At years 7 and 6, mean (median) FVIII activity (chromogenic assay) was 16.2 (10.3) and 6.7 (7.2) IU/dL in the 6 × 10<sup>13</sup> (<i>n</i> = 5) and 4 × 10<sup>13</sup> (<i>n</i> = 4) cohorts, respectively, corresponding to mild haemophilia. Regression analyses of the last year estimated rate of change in FVIII activity was -0.001 and -0.07 IU/dL/week for the 6 × 10<sup>13</sup> and 4 × 10<sup>13</sup> cohorts, respectively. Two participants (6 × 10<sup>13</sup>) resumed prophylaxis in year 7: one after a non-treatment-related G4 serious AE of spontaneous internal carotid artery bleed, and the other to manage bleeds and FVIII activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The safety and efficacy of valoctocogene roxaparvovec remain generally consistent with previous reports, with good haemostatic control for most participants. Two participants returned to prophylaxis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 5","pages":"1138-1147"},"PeriodicalIF":3.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554631","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}
S Julia Wu, Nicholas J. Cacciola-Price, Ilene Goldberg, Maria T. DeSancho
Introduction
The management of Factor XI deficiency is challenged by a variable association between FXI level and bleeding phenotype. Additionally, there is scarce data describing management strategies and their outcomes, specifically bleeding, thrombosis, and other complications.
Aims
To evaluate bleeding, thrombosis, and other complications in individuals with severe FXI deficiency seen in our comprehensive haemophilia treatment centre (HTC). Peri-procedural management strategies and the resulting impact on bleeding and other clinically relevant outcomes were reported.
Methods
Retrospective review of the electronic medical record of adult patients with severe FXI deficiency (< 20% activity) seen at a New York City comprehensive HTC between 2017 and 2022. Procedures, haemostatic management, and outcomes were collected and analysed.
Results
We identified 38 individuals (64%) females with severe FXI deficiency. The mean age was 56 ± 21 years (SD). The median FXI activity level was 3% (IQR: 1–8%). The mean BAT score was 3.1 ± 2.4; (52%) individuals did not have a history of bleeding. A total of 256 surgeries and procedures were performed. There was reduced bleeding with preventative or reactive treatment during procedures. Arterial but not venous thrombotic complications were observed. Plasma was mostly used for procedures associated with higher risk of bleeding and antifibrinolytics for procedures at sites of high fibrinolysis.
Conclusions
Current management strategies pose a burden of care for these patients and manifested as nonbleeding adverse events and changes in clinical management. These findings highlight the need for novel investigation in predicting and managing bleeding for individuals with severe FXI deficiency.
{"title":"Real world management of individuals with severe FXI deficiency and its impact on clinical outcomes: Experience from a haemophilia treatment centre","authors":"S Julia Wu, Nicholas J. Cacciola-Price, Ilene Goldberg, Maria T. DeSancho","doi":"10.1111/hae.15075","DOIUrl":"10.1111/hae.15075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The management of Factor XI deficiency is challenged by a variable association between FXI level and bleeding phenotype. Additionally, there is scarce data describing management strategies and their outcomes, specifically bleeding, thrombosis, and other complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To evaluate bleeding, thrombosis, and other complications in individuals with severe FXI deficiency seen in our comprehensive haemophilia treatment centre (HTC). Peri-procedural management strategies and the resulting impact on bleeding and other clinically relevant outcomes were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective review of the electronic medical record of adult patients with severe FXI deficiency (< 20% activity) seen at a New York City comprehensive HTC between 2017 and 2022. Procedures, haemostatic management, and outcomes were collected and analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 38 individuals (64%) females with severe FXI deficiency. The mean age was 56 ± 21 years (SD). The median FXI activity level was 3% (IQR: 1–8%). The mean BAT score was 3.1 ± 2.4; (52%) individuals did not have a history of bleeding. A total of 256 surgeries and procedures were performed. There was reduced bleeding with preventative or reactive treatment during procedures. Arterial but not venous thrombotic complications were observed. Plasma was mostly used for procedures associated with higher risk of bleeding and antifibrinolytics for procedures at sites of high fibrinolysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Current management strategies pose a burden of care for these patients and manifested as nonbleeding adverse events and changes in clinical management. These findings highlight the need for novel investigation in predicting and managing bleeding for individuals with severe FXI deficiency.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 5","pages":"1164-1169"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476475","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}
Vuokko Nummi, Leena Hiltunen, Timea Szanto, Eira Poikonen, Anna-Elina Lehtinen
Introduction
Acquired haemophilia A (AHA) is a bleeding disorder caused by autoantibody development against factor VIII (FVIII). Studies on AHA have mainly focused on patients treated at specialist centres.
Aim
To determine the incidence, clinical characteristics and outcomes of AHA in an unselected population-based patient cohort from Finland.
Methods
This retrospective observational cohort comprised all cases diagnosed with AHA in Finland between 2006 and 2019. Patients were identified by the two central laboratories performing FVIII antibody testing in Finland, the Finnish Red Cross Blood Service and HUSLAB. Clinical details were collected from all hospitals and healthcare units where patients were treated. This study was performed in conjunction with the AHA in the Nordics study.
Results
The median incidence of AHA was 0.65 per million per year (range 0.19-1.27). Fifty-five patients were identified, with a median age of 76 years and an even sex ratio (51% women). When diagnosed, all had bleeding symptoms with severe bleeds in 92%. First-line immunosuppressive treatment regimens included steroid monotherapy in 31% of cases, steroids and a cytotoxic agent in 51% and a rituximab-based regimen in 16%. Clinical remission was achieved in 71% of cases, and 15% had relapses. Mortality was 13% for bleeds and 9% for treatment-related infections. Overall survival was 64% for 1 year and 56% for 2 years after diagnosis.
Conclusions
In a nationwide population-based cohort study, we discovered a lower incidence of AHA than previously reported. Mortality among patients with AHA was high, calling for the consideration of updated treatment strategies.
导言：获得性血友病 A（AHA）是一种由针对因子 VIII（FVIII）的自身抗体引起的出血性疾病。关于AHA的研究主要集中于在专科中心接受治疗的患者。目的：在芬兰一个未经选择的人群患者队列中确定AHA的发病率、临床特征和预后：该回顾性观察队列包括 2006 年至 2019 年期间芬兰确诊为 AHA 的所有病例。患者由芬兰两家进行 FVIII 抗体检测的中央实验室（芬兰红十字血液服务机构和 HUSLAB）确定。从患者接受治疗的所有医院和医疗单位收集临床细节。这项研究与北欧 AHA 研究同时进行：AHA的中位发病率为每年每百万人中有0.65人（范围为0.19-1.27）。共发现 55 名患者，中位年龄为 76 岁，男女比例均衡（女性占 51%）。确诊时，所有患者都有出血症状，92%的患者出血严重。一线免疫抑制治疗方案包括：31%的病例采用类固醇单药治疗，51%的病例采用类固醇和细胞毒药物治疗，16%的病例采用利妥昔单抗治疗方案。71%的病例获得了临床缓解，15%的病例复发。13%的患者因出血而死亡，9%的患者因治疗相关感染而死亡。确诊后1年和2年的总生存率分别为64%和56%：在一项基于全国人口的队列研究中，我们发现 AHA 的发病率低于之前的报道。AHA患者的死亡率很高，因此需要考虑更新治疗策略。
{"title":"Acquired haemophilia A in Finland: A nationwide study of incidence, treatment and outcomes","authors":"Vuokko Nummi, Leena Hiltunen, Timea Szanto, Eira Poikonen, Anna-Elina Lehtinen","doi":"10.1111/hae.15037","DOIUrl":"10.1111/hae.15037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Acquired haemophilia A (AHA) is a bleeding disorder caused by autoantibody development against factor VIII (FVIII). Studies on AHA have mainly focused on patients treated at specialist centres.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To determine the incidence, clinical characteristics and outcomes of AHA in an unselected population-based patient cohort from Finland.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective observational cohort comprised all cases diagnosed with AHA in Finland between 2006 and 2019. Patients were identified by the two central laboratories performing FVIII antibody testing in Finland, the Finnish Red Cross Blood Service and HUSLAB. Clinical details were collected from all hospitals and healthcare units where patients were treated. This study was performed in conjunction with the AHA in the Nordics study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median incidence of AHA was 0.65 per million per year (range 0.19-1.27). Fifty-five patients were identified, with a median age of 76 years and an even sex ratio (51% women). When diagnosed, all had bleeding symptoms with severe bleeds in 92%. First-line immunosuppressive treatment regimens included steroid monotherapy in 31% of cases, steroids and a cytotoxic agent in 51% and a rituximab-based regimen in 16%. Clinical remission was achieved in 71% of cases, and 15% had relapses. Mortality was 13% for bleeds and 9% for treatment-related infections. Overall survival was 64% for 1 year and 56% for 2 years after diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In a nationwide population-based cohort study, we discovered a lower incidence of AHA than previously reported. Mortality among patients with AHA was high, calling for the consideration of updated treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 5","pages":"1130-1137"},"PeriodicalIF":3.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467444","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}
Cecilia Augustsson, Karin Strandberg, Marianne Kjalke
Introduction
Non-factor replacement therapies are emerging as prophylactic treatment options in haemophilia A or B (HA/HB) with and without inhibitors. Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody preventing factor (F)Xa inhibition and enhancing thrombin generation. Based on experience with other non-factor therapies and extended half-life products, there is a focus on potential interference with common clinical coagulation assays used to monitor patients treated with concizumab.
Aim
To evaluate the impact of concizumab on standard clinical coagulation assays.
Methods
Plasma samples (normal, HA/HB with/without inhibitors) in the presence/absence of added concizumab (250–16,000 ng/mL) were analysed in clinical assays including activated partial thromboplastin time (aPTT), prothrombin time (PT), FVIII and FIX one-stage clot and chromogenic substrate assay, assays for detecting FVIII or FIX inhibitors and other assays for coagulation factors.
Results
Concizumab did not impact PT assays, but resulted in a small shortening of aPTT (up to 5 s in haemophilia plasma and 0.4 s in normal plasma). Concizumab had no, or only a minor impact on FVIII and FIX activity assays or Bethesda inhibitor assays. FXI and FXII activity in normal plasma, as measured by single factor aPTT-based assay, was significantly increased in the presence of concizumab (+11% each). This was also the case for FVII and FX measured by PT-based assays using plasma with 25% of FVII or FX (+64% and +22%, respectively).
Conclusion
The presence of concizumab did not, or only slightly, influence the outcome of standard clinical coagulation assays relevant for HA and HB.
{"title":"Minimal interference of concizumab with standard clinical coagulation laboratory assays – An in vitro study","authors":"Cecilia Augustsson, Karin Strandberg, Marianne Kjalke","doi":"10.1111/hae.15070","DOIUrl":"10.1111/hae.15070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Non-factor replacement therapies are emerging as prophylactic treatment options in haemophilia A or B (HA/HB) with and without inhibitors. Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody preventing factor (F)Xa inhibition and enhancing thrombin generation. Based on experience with other non-factor therapies and extended half-life products, there is a focus on potential interference with common clinical coagulation assays used to monitor patients treated with concizumab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the impact of concizumab on standard clinical coagulation assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma samples (normal, HA/HB with/without inhibitors) in the presence/absence of added concizumab (250–16,000 ng/mL) were analysed in clinical assays including activated partial thromboplastin time (aPTT), prothrombin time (PT), FVIII and FIX one-stage clot and chromogenic substrate assay, assays for detecting FVIII or FIX inhibitors and other assays for coagulation factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Concizumab did not impact PT assays, but resulted in a small shortening of aPTT (up to 5 s in haemophilia plasma and 0.4 s in normal plasma). Concizumab had no, or only a minor impact on FVIII and FIX activity assays or Bethesda inhibitor assays. FXI and FXII activity in normal plasma, as measured by single factor aPTT-based assay, was significantly increased in the presence of concizumab (+11% each). This was also the case for FVII and FX measured by PT-based assays using plasma with 25% of FVII or FX (+64% and +22%, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The presence of concizumab did not, or only slightly, influence the outcome of standard clinical coagulation assays relevant for HA and HB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 4","pages":"1059-1066"},"PeriodicalIF":3.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456345","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}
Qian Su, Yashuang Shao, Yunchun Bao, Yanan Kan, Bainv Wu, Fuying Ye
Introduction
Total joint replacement is the optimal treatment option for patients with severe haemophilic arthritis. Current research emphasizes patient-reported outcomes as a vital measure for evaluating surgical outcomes and patient satisfaction. Nevertheless, very limited information about the subjective experience of perioperative haemophiliacs in the literature, highlighting the need for exploration in this area.
Aim
To investigate the psychological experiences and health demands of haemophilic arthropathy patients during the perioperative period of total joint replacement.
Design
Qualitative descriptive research with semistructured individual interviews.
Methods
From June to September 2023, nine patients with severe haemophilic arthropathy who underwent total joint replacement at a Haemophilia Diagnosis and Treatment Centre in China were interviewed for average 37 min per person. Data were analysed using the traditional content analysis method and reported following the consolidated criteria for reporting qualitative research. The study is reported according to the COREQ checklist.
Results
Interviews described two main themes: (1) emotional decline which involves preoperative overoptimism, early postoperative anxiety and disease uncertainty during the early independent rehabilitation. (2) wellness aspiration which includes rehabilitation support and spiritual healing.
Conclusion
This study reveals the patients’ significant psychological changes and their well-being aspiration, particularly out-of-hospital rehabilitation needs. Strengthening communication between multidisciplinary teams and patients, enhancing the involvement of nurses, broadening the scope of functions at primary Haemophilia Treatment Centres, and developing telerehabilitation, these concerted efforts may improve the overall treatment experience for patients.
{"title":"A qualitative study on the perioperative experiences and demands of haemophilic arthropathy patients undergoing total joint replacement","authors":"Qian Su, Yashuang Shao, Yunchun Bao, Yanan Kan, Bainv Wu, Fuying Ye","doi":"10.1111/hae.15073","DOIUrl":"10.1111/hae.15073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Total joint replacement is the optimal treatment option for patients with severe haemophilic arthritis. Current research emphasizes patient-reported outcomes as a vital measure for evaluating surgical outcomes and patient satisfaction. Nevertheless, very limited information about the subjective experience of perioperative haemophiliacs in the literature, highlighting the need for exploration in this area.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate the psychological experiences and health demands of haemophilic arthropathy patients during the perioperative period of total joint replacement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Qualitative descriptive research with semistructured individual interviews.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From June to September 2023, nine patients with severe haemophilic arthropathy who underwent total joint replacement at a Haemophilia Diagnosis and Treatment Centre in China were interviewed for average 37 min per person. Data were analysed using the traditional content analysis method and reported following the consolidated criteria for reporting qualitative research. The study is reported according to the COREQ checklist.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Interviews described two main themes: (1) emotional decline which involves preoperative overoptimism, early postoperative anxiety and disease uncertainty during the early independent rehabilitation. (2) wellness aspiration which includes rehabilitation support and spiritual healing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study reveals the patients’ significant psychological changes and their well-being aspiration, particularly out-of-hospital rehabilitation needs. Strengthening communication between multidisciplinary teams and patients, enhancing the involvement of nurses, broadening the scope of functions at primary Haemophilia Treatment Centres, and developing telerehabilitation, these concerted efforts may improve the overall treatment experience for patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 4","pages":"1050-1058"},"PeriodicalIF":3.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456324","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}
Michael Shu, Caroline Malcolmson, Alessandra Bosch, Teodora Markovic, Cindy Wakefield, Vanessa Bouskill, Manuel Carcao
Introduction
Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold-standard, however it is reserved for individuals with a high suspicion of carrier status.
Aims
To describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIX:C) levels in HB carriers and assess the ratio of FIX:C to other Vitamin K dependent factors (FII:C, FVII:C, FX:C) as an indicator of HB carrier status.
Methods
In this retrospective, single-centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIX:C were described and the relationship between FIX:C levels in carriers and severity of familial HB was analysed. Ratios of FIX:C to FII:C, FVII:C, FX:C were calculated.
Results
Seventy-two female HB carriers (median age: 34 years; IQR 24–43) were included. Median aPTT and FIX:C levels were 33.0 s [IQR 30.0–37.0] and 57 IU/dL [IQR 43–74]. Fifteen carriers (21%) had mild HB (FIX:C levels of 10–40 IU/dL). FIX:C levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIX:C to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75.
Conclusion
aPTT and FIX:C levels were unreliable in diagnosing HB carrier status. A low ratio of FIX:C to other Vitamin K dependent factors may be a useful marker of HB carrier status.
{"title":"Identifying hemophilia B carriers: Utility of aPTT, factor IX levels and ratios of factor IX to other Vitamin K dependent factors","authors":"Michael Shu, Caroline Malcolmson, Alessandra Bosch, Teodora Markovic, Cindy Wakefield, Vanessa Bouskill, Manuel Carcao","doi":"10.1111/hae.15068","DOIUrl":"10.1111/hae.15068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold-standard, however it is reserved for individuals with a high suspicion of carrier status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIX:C) levels in HB carriers and assess the ratio of FIX:C to other Vitamin K dependent factors (FII:C, FVII:C, FX:C) as an indicator of HB carrier status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective, single-centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIX:C were described and the relationship between FIX:C levels in carriers and severity of familial HB was analysed. Ratios of FIX:C to FII:C, FVII:C, FX:C were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-two female HB carriers (median age: 34 years; IQR 24–43) were included. Median aPTT and FIX:C levels were 33.0 s [IQR 30.0–37.0] and 57 IU/dL [IQR 43–74]. Fifteen carriers (21%) had mild HB (FIX:C levels of 10–40 IU/dL). FIX:C levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIX:C to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>aPTT and FIX:C levels were unreliable in diagnosing HB carrier status. A low ratio of FIX:C to other Vitamin K dependent factors may be a useful marker of HB carrier status.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 4","pages":"1003-1009"},"PeriodicalIF":3.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456326","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}
Arman Vahabi, Erdem Er, Elcil Kaya Biçer, Fahri Şahin, Kaan Kavakli, Semih Aydoğdu
Introduction
In total knee arthroplasty (TKA), choosing the correct implant size is important. There is lack of data on accuracy of templating on haemophilic knees. Our aim was to test the accuracy of 2D digital templating for TKA on haemophilic arthropathy (HA) of knee.
Materials and Methods
TKAs performed on HA between January 2011 and January 2022 were screened. Osteoarthritis (OA) group was created as control group by a one-to-one matching regarding type of implant used. Intra- and interobserver correlations were measured in HA, then correlation between templated and implanted sizes was investigated in four assessments (femur AP, femur lateral, tibia AP, tibia lateral), then compared with OA group. Fifty-eight knees in each group included.
Results
Regarding intraobserver correlation in HA, there was excellent correlation for femur AP [.93 (.73–.98)], femur lateral [.98 (.91–.99)], and tibia AP (1.0) templating. Regarding interobserver correlation in HA, excellent correlation was observed for femur lateral [.93 (.74–.98)] and tibia AP templating [.90 (.65–.97)]. Regarding correlation of templated and applied sizes in HA; tibia AP, tibia lateral and femur lateral templating showed good correlation [.81 (.70–.89), .86 (.77–.91), .79 (.67–.87) while femur AP templating showed moderate correlation [.67 (.50–.79)]. Comparing HA and OA, there was no difference in correlation levels regarding femur AP, femur lateral, tibia AP and tibia lateral templating (p = .056, p = .781, p = .761, p = .083, respectively).
Conclusion
Although 2D digital templating shows comparable correlation in HA and OA, clinical applicability of templating on HA appears to be limited in its current state.
{"title":"Accuracy and clinical role of digital templating for total knee arthroplasty performed on haemophilic knees","authors":"Arman Vahabi, Erdem Er, Elcil Kaya Biçer, Fahri Şahin, Kaan Kavakli, Semih Aydoğdu","doi":"10.1111/hae.15072","DOIUrl":"10.1111/hae.15072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In total knee arthroplasty (TKA), choosing the correct implant size is important. There is lack of data on accuracy of templating on haemophilic knees. Our aim was to test the accuracy of 2D digital templating for TKA on haemophilic arthropathy (HA) of knee.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>TKAs performed on HA between January 2011 and January 2022 were screened. Osteoarthritis (OA) group was created as control group by a one-to-one matching regarding type of implant used. Intra- and interobserver correlations were measured in HA, then correlation between templated and implanted sizes was investigated in four assessments (femur AP, femur lateral, tibia AP, tibia lateral), then compared with OA group. Fifty-eight knees in each group included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Regarding intraobserver correlation in HA, there was excellent correlation for femur AP [.93 (.73–.98)], femur lateral [.98 (.91–.99)], and tibia AP (1.0) templating. Regarding interobserver correlation in HA, excellent correlation was observed for femur lateral [.93 (.74–.98)] and tibia AP templating [.90 (.65–.97)]. Regarding correlation of templated and applied sizes in HA; tibia AP, tibia lateral and femur lateral templating showed good correlation [.81 (.70–.89), .86 (.77–.91), .79 (.67–.87) while femur AP templating showed moderate correlation [.67 (.50–.79)]. Comparing HA and OA, there was no difference in correlation levels regarding femur AP, femur lateral, tibia AP and tibia lateral templating (<i>p</i> = .056, <i>p</i> = .781, <i>p</i> = .761, <i>p</i> = .083, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although 2D digital templating shows comparable correlation in HA and OA, clinical applicability of templating on HA appears to be limited in its current state.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 4","pages":"1043-1049"},"PeriodicalIF":3.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506954","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}
Antonio Coppola, Flora Peyvandi, Laura Banov, Dorina Cultrera, Maurizio Margaglione, Alberto Tosetto, Lelia Valdrè, Irene Schiavetti, Anna Loraschi, Giancarlo Castaman, Ideal Study Group
<p>Recombinant factor IX-albumin fusion protein (rIX-FP, Albutrepenonacog alfa) is an extended half-life factor IX (FIX) with approximately 5-fold longer half-life compared to standard half-life (SHL) FIX and provides excellent bleeding prevention with a great flexibility in dosing intervals.<span><sup>1</sup></span> rIX-FP is approved for the treatment of persons with haemophilia B (PWHB) at dosing intervals of 7 days in <12 years, up to 14 days in ≥12 years and, in selected adults, up to 21 days.<span><sup>2</sup></span> However, available real-world evidence about prophylaxis regimen ≥14 days is limited. The observational study IDEAL (IDelvion in hEmophilia B: evaluAtion of posoLogic profile) described pattern of use and outcomes of rIX-FP prophylaxis in the clinical practice in moderate/severe PWHB (FIX ≤ 5%). The first phase (Part A) involved 23 Italian hemophilia treating centers (HTC) enrolling from October 2017 to February 2019 59 PWHB of all ages with a 2-year follow-up observation.<span><sup>3</sup></span> Herein, we present the subsequent phase of the study, Part B, specifically aimed at gathering real-world experience on adult PWHB on prophylaxis regimen with dosing intervals ≥14 days.</p><p>IDEAL Part B prospectively (1-year follow-up, 1YFU) collected, from April 2021 to December 2022, data about PWHB ≥18 years on dosing regimen ≥ 14 days at baseline, treated with rIX-FP ≥6 months, either previously involved in the Part A or not. The study was approved by the ethics committee at each participating centre and conducted in accordance with good clinical practice and local regulatory requirements. All patients provided written informed consent. Primary endpoints (EP) were infusion frequency, annualized number of infusions, FIX annualized consumption. Secondary EP included FIX trough levels (when measured), Annualized Bleeding Rate (ABR), rIX-FP haemostatic efficacy, presence of target joints (i.e., occurrence of ≥3 spontaneous bleeds into a single joint within a consecutive 6-month period<span><sup>4</sup></span>), chronic synovitis—assessed through physical examination (World Federation of Haemophilia, WFH, Orthopaedic Joint Score<span><sup>5</sup></span>) and, when available, ultrasound scanning according to the HEAD-US (Haemophilia Early Arthropathy Detection with Ultrasound<span><sup>6</sup></span>) protocol—chronic joint pain, physical activity, tolerability, and immunogenicity. Previous FIX data were retrospectively gathered (from Part A, or <i>de novo</i>, for new patients) and compared to rIX-FP at 1YFU. Patients were asked to fill in an infusion diary throughout the observational period including information on date, duration of each infusion, IU infused, reasons for infusion and site of bleeding, if any; each bleeding event reported in the patient diary was confirmed after discussion with the treating physician. According to physical activity, patients were considered as “sedentary” in case of no activity performed at all, “
{"title":"Real-world experience of rIX-FP prophylaxis at dosing intervals of 14 days or more in adult patients with haemophilia B in Italy – Results from IDEAL Part B","authors":"Antonio Coppola, Flora Peyvandi, Laura Banov, Dorina Cultrera, Maurizio Margaglione, Alberto Tosetto, Lelia Valdrè, Irene Schiavetti, Anna Loraschi, Giancarlo Castaman, Ideal Study Group","doi":"10.1111/hae.15074","DOIUrl":"10.1111/hae.15074","url":null,"abstract":"<p>Recombinant factor IX-albumin fusion protein (rIX-FP, Albutrepenonacog alfa) is an extended half-life factor IX (FIX) with approximately 5-fold longer half-life compared to standard half-life (SHL) FIX and provides excellent bleeding prevention with a great flexibility in dosing intervals.<span><sup>1</sup></span> rIX-FP is approved for the treatment of persons with haemophilia B (PWHB) at dosing intervals of 7 days in <12 years, up to 14 days in ≥12 years and, in selected adults, up to 21 days.<span><sup>2</sup></span> However, available real-world evidence about prophylaxis regimen ≥14 days is limited. The observational study IDEAL (IDelvion in hEmophilia B: evaluAtion of posoLogic profile) described pattern of use and outcomes of rIX-FP prophylaxis in the clinical practice in moderate/severe PWHB (FIX ≤ 5%). The first phase (Part A) involved 23 Italian hemophilia treating centers (HTC) enrolling from October 2017 to February 2019 59 PWHB of all ages with a 2-year follow-up observation.<span><sup>3</sup></span> Herein, we present the subsequent phase of the study, Part B, specifically aimed at gathering real-world experience on adult PWHB on prophylaxis regimen with dosing intervals ≥14 days.</p><p>IDEAL Part B prospectively (1-year follow-up, 1YFU) collected, from April 2021 to December 2022, data about PWHB ≥18 years on dosing regimen ≥ 14 days at baseline, treated with rIX-FP ≥6 months, either previously involved in the Part A or not. The study was approved by the ethics committee at each participating centre and conducted in accordance with good clinical practice and local regulatory requirements. All patients provided written informed consent. Primary endpoints (EP) were infusion frequency, annualized number of infusions, FIX annualized consumption. Secondary EP included FIX trough levels (when measured), Annualized Bleeding Rate (ABR), rIX-FP haemostatic efficacy, presence of target joints (i.e., occurrence of ≥3 spontaneous bleeds into a single joint within a consecutive 6-month period<span><sup>4</sup></span>), chronic synovitis—assessed through physical examination (World Federation of Haemophilia, WFH, Orthopaedic Joint Score<span><sup>5</sup></span>) and, when available, ultrasound scanning according to the HEAD-US (Haemophilia Early Arthropathy Detection with Ultrasound<span><sup>6</sup></span>) protocol—chronic joint pain, physical activity, tolerability, and immunogenicity. Previous FIX data were retrospectively gathered (from Part A, or <i>de novo</i>, for new patients) and compared to rIX-FP at 1YFU. Patients were asked to fill in an infusion diary throughout the observational period including information on date, duration of each infusion, IU infused, reasons for infusion and site of bleeding, if any; each bleeding event reported in the patient diary was confirmed after discussion with the treating physician. According to physical activity, patients were considered as “sedentary” in case of no activity performed at all, “","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 4","pages":"1067-1070"},"PeriodicalIF":3.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626574","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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