Hemophilia Treatment Centers Research Articles

Challenges associated with access to recently developed hemophilia treatments in routine care: perspectives of healthcare professionals.

The treatment landscape for haemophilia continues to rapidly develop, and expectations for future treatment success are high. There is limited information on the challenges to accessing new and innovative therapies. The aim of this study was to explore challenges with accessing haemophilia treatment from the perspective of healthcare professionals (HCPs). A crosssectional study design was used. A pilot-tested, online survey was distributed to haemophilia treatment centres in Australia, Canada, France, Italy, New Zealand, Republic of Ireland, Turkey, the United States, and the United Kingdom. The questionnaire covered questions on product access, economic considerations, health technology assessment requirements, and patient organization involvement. The results were analyzed descriptively using SPSS. A total of 154 HCPs completed the questionnaire. There was heterogeneity across countries, regions, and centres regarding HCPs' knowledge of access to novel recently developed treatments. Notable limitations to access were reported such as differences in access based on age of patient and type of product, economic considerations, and the growing influence of HTA bodies. Many countries have a hemophilia patient organization that does not have a vote at the decision-making table. There is a need to empower HCPs to better understand national healthcare structures and decisions that lead to access limitations. Requirements from HTA bodies must be understood to optimally design clinical studies and value generation of treatment options. This may strengthen the haemophilia treatment centre's voice to collectively mandate for exchange with key involved individuals, such as the payers and politicians for the provision of optimal therapy.

Haemophilia testing of young girls in Canada: Describing the current recommendations for factor level and genetic testing and the experiences of Canadian parents.

It is widely acknowledged that haemophilia affects women and girls, yet current testing recommendations for factor level and genetic testing vary and do not universally incorporate updated research. Canadian parents have expressed frustration at inconsistent recommendations and reported instances where delayed testing led to missed diagnosis and preventable bleeding. Study aim was to explore and describe the practice of haemophilia-related testing of young girls in Canada. A mixed methods study was carried out with two populations: (1) Nurses working in haemophilia care completed a survey regarding the current testing recommendations of their Haemophilia Treatment Centre (HTC), (2) Parents of obligate or potential haemophilia carriers completed a structured interview with questions about their family experience of haemophilia and testing decisions for daughters. Twenty-six survey responses were received and showed wide variation in the usual recommendations of Canadian HTCs. Different factor level testing recommendations may be given to obligate and potential carriers despite no difference in bleeding risk. Only a minority of HTCs currently recommend an early baseline factor level (<10 years) to obligate carriers (27%) or potential carriers (15%). For genetic testing of potential carriers, 70% of HTC would approve a family request for genetic testing of a minor with specific conditions. The majority of parents interviewed felt dissatisfied with their testing experience (58%) and highlighted many issues related to delayed testing recommendations. Updated, nationally affirmed testing recommendations are needed that align with research on bleeding in women and girls affected by haemophilia.

Bleeding and quality of life in people with Glanzmann thrombasthenia—insights from the Glanzmann’s 360 study

BackgroundGlanzmann thrombasthenia (GT) is a rare platelet function disorder that results in severe bleeding. We assessed clinical symptoms and psychological parameters to identify the unmet needs associated with GT. ObjectivesGlanzmann’s 360 is a mixed-methods study designed to give a contemporary snapshot of the impact of living with GT. MethodsThe study comprised a self-completion online survey complemented by interviews conducted with affected individuals and carers recruited via social media and hemophilia treatment centers. ResultsThe survey was completed by 88 people with GT and 29 carers of children/young people with GT aged <16 years. The population ranged in age from <2 years to >70 years; 56% were female. Although 47% had been diagnosed with GT under the age of 2 years, 12% were diagnosed after 20 years of age. For 82%, a bleeding phenotype was apparent by the age of 5 years. Most respondents (88%) had experienced at least one bleed in the past week. Bleeding disproportionally affected women. Bleeds resulted in frequent hospital contact and considerable psychological distress: 26% of the population had scores suggestive of low self-esteem, while 30% met criteria suggestive of symptomatic depression. Exploratory analyses suggest that bleed experiences are associated with impaired health-related quality of life. ConclusionThe Glanzmann’s 360 study reveals the significant physical, psychosocial, and quality-of-life impairments that are likely to be linked to the frequent bleeds experienced by those with GT. Clinicians treating people with GT should promote access to multidisciplinary comprehensive care, including psychosocial support.

Functional evaluation of joint in moderate to severe hemophilia patients treated with on-demand factor replacement: insights from a single hemophilia treatment center in Bangladesh

BackgroundHemophilia patients are prone to spontaneous or post-traumatic bleeding, particularly in joints and various other body sites. The high incidence of joint hemorrhages in hemophilia patients underscores the importance of routine joint assessments in clinical care to monitor the condition and evaluate the efficacy of hemophilia treatments.AimThis study aimed to assess the joint health of hemophilia patients receiving FVIII or FIX on-demand replacement therapy treatment at a tertiary care hospital in Bangladesh.MethodsThis single-center study involved 93 patients diagnosed with moderate (n = 72;77.4%) and severe (n = 21;22.6%) hemophilia. The assessment of joint health was carried out on six key joints—both elbows, knees, and ankles—using the Hemophilia Joint Health Score (HJHS) version 2.1. Clinical and laboratory data were meticulously documented in a structured questionnaire.ResultsAmong the 93 hemophilic patients, the majority had hemophilia A (96.8%). The median HJHS of the patients was 15 (IQR:9.5–20) with the knee joint being mostly affected (88.2%). A significant positive correlation was observed between HJHS and age (r = 0.385, p < 0.001) and total number of joints involved (r = 0.405, p < 0.001). No significant association was found between factor level, education status, and socio-economic status with HJHS score.ConclusionEarly assessment and monitoring of joint health are essential in clinical practice to prevent severe complications in hemophilia patients.

Real‐world effectiveness of eptacog beta in patients with haemophilia and inhibitors: A multi‐institutional case series

AbstractIntroductionThe management of bleeding events (BEs) in haemophilia A (HA) and B (HB) patients with inhibitors necessitates the use of bypassing agents. The recombinant factor VIIa bypassing agent eptacog beta has demonstrated efficacy at treating BEs and managing perioperative bleeding in adults in phase three clinical studies.AimTo provide real‐world descriptions of eptacog beta use for BE treatment in patients on emicizumab or eptacog beta prophylaxis.MethodsThis is a retrospective case series of 14 patients who received eptacog beta at seven haemophilia treatment centres, with HA (n = 11) or HB (n = 3) and inhibitors or anaphylaxis to factor replacement.ResultsTwenty‐four spontaneous and traumatic BEs are described (muscle hematomas, joint hemarthroses, port site, and epistaxis) involving 11 subjects. Eptacog beta was effective for acute bleed treatment as both first‐line therapy and for treatment of BEs refractory to eptacog alfa in 23/24 events. When eptacog beta was used for prophylaxis, 2/3 patients reported a decreased frequency of breakthrough BEs compared with prophylactic eptacog alfa and one patient experienced a similar frequency of breakthrough BEs compared with prophylactic activated prothrombin complex concentrate. Eptacog beta provided effective bleed control for three subjects who underwent minor surgical procedures. Treatment with eptacog beta was estimated to be 46%–72% more cost‐effective than eptacog alfa. No safety concerns or adverse events were reported.ConclusionsIn this case series, eptacog beta was safe, effective, and economical as first‐line therapy, treatment of refractory BEs, management of perioperative bleeding, or prophylaxis in haemophilia patients with inhibitors.

Toward Personalized Care and Patient Empowerment and Perspectives on a Personal Health Record in Hemophilia Care: Qualitative Interview Study.

To enable personalized treatment and shared decision-making in chronic care, relevant health information is collected. However, health information is often fragmented across hospital information systems, digital health apps, and questionnaire portals. This also pertains to hemophilia care, in which scattered information hampers integrated care. We intend to co-design a nationwide digital personal health record (PHR) for patients to help manage their health information. For this, user perspectives are crucial. This study aims to assess patients' and health care providers' perspectives regarding the use of a PHR in hemophilia care in the Netherlands, required functionalities, and expectations and concerns. In this semistructured interview study, 19 pediatric and adult persons with hemophilia, parents, and women with other inherited bleeding disorders, as well as 18 health care providers working within and outside of hemophilia treatment centers, participated. Perspectives of patients and providers were explored separately. To explore requirements, participants were asked to prioritize functionalities. Participants expected a PHR would increase the transparency of health information, improve patients' understanding of their illness, and help the coordination of care between health care providers and institutions. Prioritized functionalities included the integration of relevant health information and patient-entered data. Formulated expectations and concerns focused on 4 themes: usability, safety, inclusiveness, and implementation. While patients expressed worries over medicalization (ie, more confrontational reminders of their illness), providers were concerned about an increased workload. People with hemophilia, their parents, and health care providers welcomed the development of a PHR, as they expected it would result in better coordinated care. Formulated expectations and concerns will contribute to the successful development of a PHR for persons with hemophilia, and ultimately, for all persons with a chronic condition.

Clinical validation and application of targeted long-range polymerase chain reaction and long-read sequencing–based analysis for hemophilia: experience from a hemophilia treatment center in China

BackgroundTargeted long-read sequencing (LRS) is expected to comprehensively analyze diverse complex variants in hemophilia A (HA) and hemophilia B (HB) caused by the F8 and F9 genes, respectively. However, its clinical applicability still requires extensive validation. ObjectivesTo evaluate the clinical applicability of targeted LRS-based analysis compared with routine polymerase chain reaction (PCR)–based methods. MethodsGene variants of retrieved subjects were retrospectively and prospectively analyzed. Whole-genome sequencing was performed to further analyze undiagnosed cases. Breakpoints of novel genomic rearrangements were mapped and validated using long-distance PCR and long-range PCR combined with sequencing. ResultsIn total, 122 subjects were retrieved. In retrospective analysis of the 90 HA cases, HA-LRS assay showed consistent results in 84 cases compared with routine methods and characterized 6 large deletions with their exact breakpoints confirmed by further validation in 6 cases (routine methods only presented failure in amplifying the involved exons). In prospective analysis of the 21 HA subjects, 20 variants of F8 were identified in 20 cases. For the remaining HA patient, no duplication/deletion or single-nucleotide variant (SNV)/insertion and deletion (InDel) was found, but a potential recombination involving exons 14 and 21 of F8 was observed by LRS. Whole-genome sequencing analysis and further verification defined a 30 478 base pairs (bp) tandem repeat involving exons 14 to 21 of F8. Among the 11 HB patients, HB-LRS analysis detected 11 SNVs/InDels in F9, consistent with routine methods. ConclusionTargeted LRS-based analysis was efficient and comprehensive in identifying SNVs/InDels and genomic rearrangements of hemophilia genes, especially when we first expanded the panel to include F9. However, further investigation for complex gross rearrangement is still essential.

Investigation and Analysis of the Current Status of Health-Related Quality of Life in Adolescents with Hemophilia in Hubei Province.

Aims/Background Reliable health-related quality of life data are critical in developing countries, in order to advocate for government agencies to develop national hemophilia care programmes. This study aims to explore the current status and influencing factors of health-related quality of life among adolescents with hemophilia in Hubei Province, so as to provide empirical data for professionals. Methods A total of 84 children with hemophilia aged 8 to 18, who were registered in Tongji Hemophilia Treatment Center and Hubei Hemophilia Home, were selected using a cluster sampling method. The "General Situation Questionnaire of Hemophiliac Adolescents", designed by Tongji Hemophilia Treatment Center, and "the Chinese version of Canadian hemophilia outcomes-kid's life assessment tool (CHO-KLAT)", were used for this study conducted from June 1, 2022 to December 30, 2022. Results 82 completed questionnaires were included. The average age of the 82 adolescents was 13.04 ± 3.29 years and all were males. Among them, 67 were hemophilia A and 15 were hemophilia B. 61 cases were severe type, 19 were moderate type and 2 cases were mild type. The average total score of the CHO-KLAT for adolescents with hemophilia in Hubei Province was 49.49, which was lower than their counterparts in developed countries. The statistically significant influencing factors included residence, annual family income, and disease type. Conclusion This study provides empirical data support for the health management of adolescents with hemophilia, highlighting the importance of improving medical resource access, transfusion convenience, and psychological support in enhancing the quality of life for this group. The results emphasize the need for healthcare systems and policymakers to take specific measures to address these factors to improve the treatment and care conditions for adolescents with hemophilia.

Differences and similarities in patient-reported outcomes among men and women with haemophilia.

Both men and women can be diagnosed with haemophilia and the experience with haemophilia may be different between men and women. This study aimed to compare patient-reported outcomes in men versus women with haemophilia. This cross-sectional study is a post-hoc analysis of data collected as part of the Haemophilia-related Distress Questionnaire validation study. Adults aged ≥18 years with haemophilia A or B were recruited from one of two haemophilia treatment centres between July 2017 and December 2019. Outcomes included quality of life, measures of mental and physical health, and overall health. Unadjusted and multivariable linear regression models were used to examine potential mediators of sex-based differences in outcomes. Of the 139 study participants included (21 women, 118 men), the mean age was 36.9 years and most (89.2%) had haemophilia A. Approximately 85.7% and 26.3% of women and men had mild haemophilia, respectively. PHQ-9 depression and PROMIS-29 Profile anxiety and fatigue scores were significantly higher in women than men in unadjusted and adjusted analyses. There were no statistically significant differences in other outcomes. Women with haemophilia are more likely to experience depression, anxiety, and fatigue than men with haemophilia. This study highlights the need for mental health services to be integrated into the care of women with haemophilia. Future research is needed to understand whether women with haemophilia are more or less likely to experience depression, anxiety, and fatigue than women without haemophilia as well as determine the impact of reduced mental health on clinical outcomes.

F8 variants and their genotype-phenotype correlations in Thai patients with haemophilia A: a nationwide multicentre study

AimsAnalysis of the F8 gene helps predict the risk of developing factor VIII (FVIII) inhibitors and the depth of phenotype in haemophilia A (HA) patients. Since data in Southeast Asian...

Real world management of individuals with severe FXI deficiency and its impact on clinical outcomes: Experience from a haemophilia treatment centre.

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. 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. 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. 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. 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.

Primary postpartum hemorrhage in women with von Willebrand disease and carriers of hemophilia: a retrospective analysis

BackgroundBetween 2002 and 2011, the incidence of severe primary postpartum hemorrhage (PPH) in Dutch women with von Willebrand disease (VWD) and hemophilia carriers (HCs) was 8% vs 4.5% in the general population. ObjectivesTo determine the contemporary incidence of severe primary PPH in women with VWD and HCs. MethodsAll women with VWD or HCs who delivered between 2012 and 2017 were selected from all 6 Dutch hemophilia treatment centers. Data on patient and disease characteristics, peripartum hematologic and obstetric management, and outcomes were retrospectively collected. Incidence of severe primary (≥1000 mL of blood loss ≤24 hours after childbirth) and primary (≥500 mL within ≤24 hours after childbirth) PPH was compared with the (1) previous cohort and (2) general Dutch population and between (3) women with VWD and HCs with third-trimester coagulation activity levels <50 international units (IU)/dL vs ≥50 IU/dL and (4) women treated with vs without peripartum hemostatic prophylaxis. ResultsThree-hundred forty-eight deliveries (151 VWD, 167 hemophilia A, and 30 hemophilia B carriers) were included. The severe primary PPH incidence was 10% (36/348) and remained stable over time, whereas this incidence has increased in the general population (to 8%), leading to a similar risk (P = .17). Severe primary PPH risk was comparable between women with coagulation activity levels <50 and ≥50 IU/dL (11% [7/66] vs 10% [29/279]; odds ratio, 1.02; 95% CI, 0.43-2.44) and comparable between those with and those without prophylaxis (12% [11/91] vs 10% [25/254]; odds ratio, 1.26; 95% CI, 0.59-2.68). ConclusionSevere primary PPH in women with VWD and HCs remained stable and is comparable with the increasing prevalence in the general population. More research is needed to find the optimal pregnancy management strategy for safe delivery in VWD and HC.

Real-world usage and effectiveness of recombinant factor VIII/factor IX Fc in hemophilia A/B: final data from the 24-month, prospective, noninterventional PREVENT study in Germany

BackgroundReal-world experience with efmoroctocog alfa (a recombinant factor [F]VIII Fc fusion protein [rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) is needed to bridge evidence gaps. ObjectivesTo describe rFVIIIFc/rFIXFc usage and effectiveness over a 24-month prospective period. MethodsPREVENT (NCT03055611), a noninterventional study across 25 German hemophilia treatment centers, enrolled previously treated persons with hemophilia A and B (all ages/severities) on individualized rFVIIIFc/rFIXFc prophylaxis before/at enrollment. Primary endpoints included annualized bleeding rate (ABR), injection frequency (IF), and factor consumption (FC). Additionally, up to 12 months of retrospective FVIII/FIX data were collected. Physician and patient satisfaction, and safety outcomes were also assessed. ResultsOverall, 150 patients received ≥1 rFVIIIFc dose and 47 patients received ≥1 rFIXFc dose, with median prospective follow-up of 20.6 and 21.0 months, respectively. rFVIIIFc/rFIXFc demonstrated low median ABR (0.5/1.7), annualized IF (121.8/52.2 injections/y), and FC (4611.7/2423.9 IU/kg) in line with product labels. Compared with previous FVIII/FIX, there was a 56.0% reduction in ABR for rFVIIIFc (rate ratio, 0.44; 95% CI, 0.31-0.64), with no change for rFIXFc (rate ratio, 0.93; 95% CI, 0.66-1.31); rFVIIIFc/rFIXFc reduced annualized IF (rFVIIIFc, mean difference, −31.7; 95% CI, −40.3 to −23.1; rFIXFc, mean difference, −37.3; 95% CI, −46.9 to −27.8), while FC remained stable (rFVIIIFc, +374.1; 95% CI, +46.8 to +701.3; rFIXFc, +503.9; 95% CI, +95.4 to +912.4). Most physicians and patients were satisfied or highly satisfied with rFVIIIFc/rFIXFc. rFVIIIFc/rFIXFc were well tolerated, with no inhibitor development or treatment-related serious adverse events. ConclusionReal-world PREVENT data complement phase 3 trials and show that individualized rFVIIIFc/rFIXFc prophylaxis provided stable bleed protection with low IF and maintained FC. Compared with previous FVIII, ABR was considerably reduced with rFVIIIFc, with stable annualized FC. For rFIXFc, bleed protection was maintained vs previous FIX while reducing annualized IF.

Genotype-Dependent Response to Desmopressin in Hemophilia A and Proposal of a Predictive Response Score.

Desmopressin (DDAVP) is used in patients with moderate/mild hemophilia A (PWMHs) to increase their factor VIII (FVIII) level and, if possible, normalize it. However, its effectiveness varies between individuals. The GIDEMHA study aims to investigate the influence of F8 gene variants. The study collected the trajectory of FVIII levels from therapeutic intravenous DDAVP tests in four French hemophilia treatment centers. A pharmacological analysis was performed associated with efficacy scores according to F8 variants: absolute and relative responses, as well as new scores: absolute duration (based on duration with FVIII ≥ 0.50 IU.mL-1) and relative duration (based on half-life). From enrolled 439 PWMHs, 327 had a hot-spot F8 variant (with ≥5 PWMHs). For these, the median (min-max) basal and peak FVIII were 0.20 (0.02-0.040) and 0.74 (0.14-2.18) IU.mL-1 respectively, with FVIII recovery being 3.80 IU.ml-1 (1.15-14.75). The median FVIII half-life was 3.9 hours (0.7-15.9 hours). FVIII was normalized (≥0.50 IU.mL-1) in 224/327 PWMHs (69%) and the median time with normalized FVIII was 3.9 hours (0.0-54.1 hours). Following the response profiles to DDAVP defined by the four efficacy scores, four groups of F8 variants were isolated, and then compared using survival curves with normalized FVIII (p < 0.0001): "long-lastingly effective" [p.(Glu739Lys), p.(Ser2030Asn), p.(Arg2178His), p.(Gln2208Glu), and T-stretch deletion in intron 13]; "moderately effective" [p.(Ser112Phe), p.(Ala219Thr), p.(Thr2105Ile), p.Phe2146Ser), and p.(Asp2150Asn)]; "moderately ineffective" [p.Ala81Asp), p.(Gln324Pro), p.(Tyr492His), p.(Arg612Cys), p.(Met701Val), p.(Val2035Asn), and p.(Arg2178Cys)]; and "frequently ineffective" [c.-219C > T, p.(Cys2040Tyr), p.(Tyr2169His), p.(Pro2319Leu), and p.(Arg2326Gln)]. In view of our data, we propose indications for DDAVP use in PWMH based on F8 variants for minor and major invasive procedures.

Present status of scheduled vaccinations and vaccination-related bleeding in Chinese children with haemophilia.

Many countries have detailed recommendations for haemophilia patients to reduce the risk of vaccination-related bleeding. However, data from developing countries are lacking. We investigated scheduled vaccinations and vaccination-related bleeding complications in Chinese children with haemophilia and analysed issues related to vaccinations. Children with haemophilia in the PUMCH Haemophilia Treatment Centre were contacted via telephone. We distributed a vaccination questionnaire to their parents. The severity of haemophilia, coagulation factor infusions before vaccination, injection mode, and vaccination-related complications were analysed. A total of 440 valid questionnaires were received from 27 of 34 provinces in China. 31.3% (138/440) of the children with haemophilia did not receive all of their vaccinations. Among the children who received vaccinations, 48.1% (197/409) experienced bleeding complications. In patients with severe haemophilia, those on regular prophylaxis had a lower incidence of local hematoma compared to those on intermittent or no prophylaxis (14.3% vs. 26.5% vs. 39.7%, P < 0.05). The incidence of local hematomas was lower by subcutaneous (SQ) injections than by intramuscular injections (24.6% vs. 35.3%, P < 0.05). The vaccination rate is quite insufficient in Chinese children with haemophilia. Missed vaccinations are related to vaccination-related bleeding complications. Prophylaxis before vaccination and SQ injections would help reduce bleeding complications.

Preference of treatment characteristics among people with haemophilia or their caregivers, and physicians in the Japanese healthcare environment.

Studies of treatment preferences in haemophilia have been conducted in many countries. This study is the first to examine treatment characteristic preferences among people with haemophilia (PWH) and their caregivers, and physicians in Japan. To examine current treatment preferences of PWH and their caregivers, plus those of physicians at haemophilia treatment centres (HTCs) and non-HTCs for different treatment characteristics in Japan. Physicians listed on a survey panel were invited to participate in the survey and to refer PWH and caregivers to participate in the survey. Web-based surveys were conducted to examine physician and PWH/caregiver background, prophylaxis background, prophylaxis goals, understanding of haemophilia treatment products, important information sources, preferences while choosing prophylaxis products, understanding of the patient's condition, and potential product switching. A discrete choice experiment exercise was included in the survey. A total of 107 physicians and 44 PWH/caregivers participated in the study. Key treatment goals of physicians included optimisation of haemophilia management. PWH/caregivers were focused on quality of life and reduced treatment burden. Consistent differences in haemophilia treatment strategies at HTCs and non-HTCs were observed for prescribed treatments, preferences in choosing prophylaxis products, understanding of patients' condition, and reasons for potential product switch. Our study utilises real-world survey data and presents preferences for haemophilia treatment characteristics among physicians, PWH and their caregivers in Japan, which could encourage improvements in individualised treatment and disease management. Alignment between treatment approaches at HTCs and non-HTCs could facilitate improvements in the quality of care for PWH across Japan.

Bleeding risk in hemophilia A and B carriers: comparison of factor levels determined using chronometric and chromogenic assays.

Predicting the bleeding risk in hemophilia A and B carriers (HAC, HBC) is challenging. The objectives of this study were to describe the bleeding phenotype in HAC and HBC using the standardized Tosetto bleeding score (BS); to determine whether the BS correlates better with factor levels measured with a chromogenic assay than with factor levels measured with chronometric and thrombin generation assays; and to compare the results in HAC and HBC. This ambispective, noninterventional study included obligate and sporadic HAC and HBC followed at a hemophilia treatment center between 1995 and 2019. The median BS (3, range 0-21 vs. 3.5, range 0-15, P = ns, respectively) and the abnormal BS rate (35.6% vs. 38.2%, P = ns) were not significantly different in 104 HAC and 34 HBC (mean age: 38 years, 6-80 years). However, some differences were identified. The risk of factor deficiency was higher in HBC than HAC. Specifically, Factor VIII activity (FVIII):C/Factor IX activity (FIX):C level was low (<40 IU/dl) in 18.3% (chronometric assay) and 17.5% (chromogenic assay) of HAC and in 47% and 72.2% of HBC ( P < 0.001). Moreover, the FIX:C level thresholds of 39.5 IU/dl (chronometric assay) and of 33.5 IU/dl (chromogenic assay) were associated with very good sensitivity (92% and 100%, respectively) and specificity (80% for both) for bleeding risk prediction in HBC. Conversely, no FVIII:C level threshold could be identified for HAC, probably due to FVIII:C level variations throughout life.

Mutational landscape, inhibitor development, and health-care burden in non-severe haemophilia A: A single-centre Australian experience.

To characterise non-severe haemophilia A (HA) patients enrolled on the Australian Bleeding Disorders Registry (ABDR) treated through a state-wide Haemophilia Treatment Centre (HTC) with respect to their mutational profile, inhibitor risk and health-care burden. We conducted a single-centre observational study of all non-severe HA patients treated at the Alfred Health HTC registered on the ABDR as of the 26thJuly 2023. Data were extracted from the ABDR and electronic medical record (EMR) regarding demographics, severity, genetic testing, treatment, inhibitors, bleeding events and procedures. Inhibitor risk was calculated as a function of exposure days (EDs) of FVIII replacement. There were 289 non-severe HA patients treated at the Alfred HTC registered on the ABDR as of July 2023, all of whom were adult patients aged>18 years old. Genotyping had been performed in 228/289 (78.9%). Of the inhibitor analysis population, 14/193 (7.3%) had an inhibitor. The cumulative incidence of inhibitor development at 75 EDs was 31% (95% CI 13%-46%). The median cost of bypassing agents per inhibitor patient was $57,087.50/year. These results demonstrate a relatively high inhibitor prevalence and incidence risk in non-severe HA compared to previously published work, although this may partly reflect a smaller population size. High rates of genotyping have allowed representative mutational characterisation. The burden of care imposed by non-severe HA in terms of bleeding events, procedures and bypassing agent cost is larger than expected, particularly within the inhibitor population.

Race and ethnicity reporting and representation in hemophilia clinical trials

AbstractRacial and ethnic representativeness in clinical trials is crucial to mitigate disparities in outcomes; however, diversity among hemophilia trials is unknown. The aim of this study is to examine the reporting and representation of race and ethnicity in trials of people with hemophilia (PwH). In this cross-sectional study, the ClinicalTrials.gov database was queried in April 2023 for interventional clinical trials involving PwH between 2007 and 2022. The distribution of participants (observed) was compared with expected proportions based on US Hemophilia Treatment Center (HTC) and country-specific census data with observed-to-expected ratios (OERs). Of 129 trials included, 94.6% were industry sponsored, with a mean of 62 participants and mean age of 26.8 years. Overall, 52.0% (n = 66) of trials reported data on race and ethnicity, increasing from 13.9% in 2007-2012 to 22.5% in 2013-2016 to 100% in 2017-2022 (P = .001). Among these 66 trials, 65.8%, 22.8%, 5.1%, 3.9% of participants were White, Asian, Hispanic, and Black, respectively. OERs were 10% to 20% lower for White participants vs US HTC, and US, UK, and Canadian census populations and ∼75% lower for Black or Hispanic participants when compared with US HTC and US census population. OERs for Asian participants were 1.6 to 3 times higher than Canada, US, and UK census populations. The reporting of race and ethnicity in hemophilia trials has drastically improved; however, Black and Hispanic PwH remain especially underrepresented. To address these disparities, stakeholders across the clinical trial enterprise need to implement strategies to ensure equitable participation.

Clinical and treatment characteristics of infants and toddlers less than 2 years of age with hemophilia

AbstractInfants and toddlers (ITs) with hemophilia have unique bleeding features. Factor prophylaxis has been shown to decrease the risk of intracranial hemorrhage (ICH), which supports recommendations to begin at a young age. Clinical and demographic characteristics were analyzed for 883 ITs ≤2 years old with hemophilia A and B, seen at US Hemophilia Treatment Centers and enrolled in the Community Counts Registry, a surveillance program of the Centers for Disease Control and Prevention. ICH in the first 2 years of life was seen in 68 of 883 (7.7%) ITs, of whom 8 of 68 (11.8%) were on continuous prophylaxis at the time of ICH. ITs in this study usually started prophylaxis within the first year of life (mean, 10.3 months), with earlier ages of prophylaxis initiation in later birth cohorts in ITs with hemophilia A. Compared with those without a family history (FH) of hemophilia, known positive FH of hemophilia was associated with earlier age of diagnosis (P ≤ .0001) and decreased rates of vaginal delivery (P = .0006). The use of factor VIII mimetics and extended half-life clotting factor prophylaxis increased with later birth cohorts for ITs with hemophilia A and B. The study highlights that ICH rates in ITs with hemophilia remains substantial and underscores the need for further research to identify modifiable risk factors to prevent ICH by earlier diagnosis and initiating prophylaxis early, even within the first month of life.