Joint Bleeding Research Articles

Study on the value of enhanced magnetic resonance imaging in the International Prophylaxis Study Group (IPSG) score of the synovium in hemophilic arthropathy

Objective: To evaluate the value of enhanced magnetic resonance imaging (MRI) on the assessment of synovial hyperplasia and International Prophylaxis Study Group (IPSG) score of hemophilic arthropathy (HA). Methods: This was a retrospective case series study. Briefly, 54 joints of 46 male patients with hemophilia type A and diagnosed with HA in Henan Provincial People's Hospital from August 2016 to September 2017 were selected. Plain and enhanced MRI were performed at the same time. The IPSG score of synovial hyperplasia and the total joint before and after enhancement were calculated, and the enhancement rate of the synovium and muscles at the same level were also calculated. The differences in synovial hyperplasia and joint total IPSG scores before and after enhancement were compared by paired rank sum test. The correlation between enhancement joint total IPSG score, synovial IPSG score, synovial enhancement rate, total joint bleeding number, course of disease, and Hemophilia Joint Health Score (HJHS) score were analyzed by Spearman's correlation analysis. Results: Enhanced MRI could more clearly show synovial hyperplasia and ensure better accuracy of joint total IPSG score (Z=-2.24, P=0.025). The enhancement extent of synovial hyperplasia was higher than that of the same level muscle. There was no correlation between synovial enhancement rate and total number of joint bleeding, course of disease, and HJHS score. After enhancement, the joint total IPSG score was highly positively correlated with the total number of joint bleeding and the disease course (r=0.96, 0.84, P<0.001) and moderately positively correlated with the HJHS score (r=0.58, P<0.001). The enhanced synovial IPSG score showed a low positive correlation with the total number of joint bleeding and the disease course (r=0.37, 0.36, P=0.006, 0.008), but no correlation with HJHS score. Conclusion: Enhanced MRI can provide accurate imaging of synovial hyperplasia of HA and make joint IPSG score more accurate.

Efanesoctocog Alfa Versus Emicizumab in Adolescent and Adult Patients With HaemophiliaA Without Inhibitors.

The phase3 XTEND-1 trial (NCT04161495) demonstrated that efanesoctocog alfa prophylaxis provided superior bleed protection compared with pre-trial factorVIII (FVIII) prophylaxis in patients with severe haemophiliaA. The aim of this study was to indirectly compare the efficacy of efanesoctocog alfa with non-factor replacement therapy emicizumab in adolescent and adult patients with severe haemophiliaA without inhibitors. A systematic literature review was conducted to identify phase3 trials of emicizumab. Matching-adjusted indirect comparisons were used to compare annualised bleeding rates (ABRs) for any, treated, joint, and spontaneous bleeds, and joint health (measured using Hemophilia Joint Health Score [HJHS]), between efanesoctocog alfa and emicizumab. Estimated effects for different emicizumab regimens were pooled using random-effect meta-analysis to evaluate the overall difference in bleed outcomes between efanesoctocog alfa and emicizumab. One emicizumab trial was included (HAVEN3), which investigated three dosing regimens. In meta-analyses, efanesoctocog alfa once-weekly (Q1W) was associated with significantly lower ABRs for any (incidence rate ratio [95%CI] 0.33 [0.20; 0.53]), any treated (0.49 [0.30; 0.80]) and treated joint (0.51 [0.28; 0.91]) bleeds compared with emicizumab Q1W in non-inhibitor patients with prior prophylaxis or on-demand treatment. Efanesoctocog alfa Q1W was also associated with a significantly better improvement from baseline in HJHS Joint Score (mean difference [95%CI] -2.06 [-3.97; -0.14]) and Total Score (-2.37 [-4.36; -0.39]) versus emicizumab Q1W or every 2weeks. Efanesoctocog alfa prophylaxis was associated with significantly lower rates of any, treated, and joint bleeds and improved joint health compared with emicizumab in patients with severe haemophiliaA.

Evaluating the Effectiveness of Prophylactic Strategies for Hemophilia A Management: A Real-World, Longitudinal Observational Study.

Hemophilia A (HA) treatment strategies aim to manage bleeding episodes and improve patients' quality of life. This study investigates the effectiveness of a preventative approach using intermediate-dose prophylaxis with standard half-life FVIII products in reducing bleeding rates and enhancing the quality of life for patients with severe HA. A 4-year prospective longitudinal study followed 35 patients with severe HA (without FVIII inhibitors) who transitioned from a reactive treatment approach to intermediate-dose prophylaxis in Taiwan from 2014 until 2018. The study tracked annual bleeding rates (ABR) and annual joint bleeding rates (AjBR) alongside associated costs and patient-reported quality-of-life measures. Prophylaxis significantly reduced both ABR and AjBR compared with the previous treatment. After one year, ABR and AjBR decreased by 76.9% and 72.5%, respectively, with further reductions to 91.0% and 90.8% after 4 years (p<0.001). While the average annual cost of factor VIII concentrate increased by 41.0% in the first year, the incremental cost-effectiveness ratio demonstrated ongoing benefits from ABR avoidance over the 4 years. Additionally, patients reported significant improvements in quality-of-life measures following the switch to prophylaxis (p=0.036). Intermediate-dose prophylaxis effectively reduced bleeding rates and improved quality of life in patients with severe HA. Despite initial cost increases, the intervention became cost effective over time. This study provides valuable data for healthcare policymakers, highlighting the long-term benefits of prophylaxis as a preventative approach for managing bleeding and improving overall well-being in patients with severe HA.

One day at a time: Life with Glanzmann thrombasthenia - Qualitative results from the GT 360 study.

Glanzmann thrombasthenia (GT) is a platelet function disorder. Symptoms include bruising and bleeding, which may be severe and life-threatening. The day-to-day experiences of those affected remain poorly documented. The Glanzmann's 360 study aimed to better understand the daily realities of living with GT, exploring psychological, social and medical challenges to identify unmet need. People with GT over 18 and caregivers of children with GT participated. Mixed methods research was used, including a survey and in-depth interviews. The interviews, reported here, were audio-recorded, transcribed and thematically analysed. Nineteen interviews were conducted; 14 with people with GT and five caregivers. Mean age of those with GT was 32.9 years (range 2-78 years). Eight themes emerged: Diagnosis, Bleeding and Treatment, Menstruation, Fatigue, Identity, Abuse, Pregnancy, and The Future. Three participants described misdiagnosis. Caregivers reported early recognition and prompt diagnosis of their children. Bruising, the most commonly reported symptom, led to assumption of abuse. Six (32%) participants reported joint bleeds. External bleeding was normalised. Access to home treatment and local care were limited. Fatigue caused by anaemia was described. All women reported heavy menstrual bleeding. Choices around pregnancy were limited by 'medical pessimism'. Nevertheless, participants remained hopeful for the development of improved treatment options. People with GT face significant and often overlooked challenges. There is need for improved medical and psychological treatment and support, increased awareness of these needs amongst healthcare professionals, and research into developing comprehensive care models that address medical and psychosocial needs of people with GT.

The Real-World Data of Emicizumab in Previously Untreated and Minimally Treated Patients with Hemophilia a Infants from China

Introduction Emicizumab (EMI) is safe and efficient in pediatric patients with hemophilia A (HA). However, real-world data regarding immune response, pharmacokinetics (PK) and pharmacodynamics (PD) during EMI for previously untreated (PUP) and minimally treated (MTP) patients with HA infants(&amp;lt;3y) are limited in China. This study investigated the immune response and PK/PD of EMI in PUP and MTP with HA infants in China. Methods We performed a retrospective analysis of pediatric HA patients to collect data on PUPs and MTPs at our Comprehensive Hemophilia Care Center. Data included patients' baseline characteristics, therapy details, bleeding episode of pre- and post-EMI, and adverse events. Immune response included anti-emicizumab antibodies (ADAs) and factor VIII (FVIII) inhibitors. Laboratory analyses included FVIII-like activity and EMI concentration measurements. Results Sixteen PUPs and MTPs with HA had received EMI prophylaxis for a median (range) duration of 21.8 (4.9-47.0) months by July 2024. The median age at the beginning of EMI was 11.8 (5.8-33.3) months. At the initiation of EMI, all patients were inhibitor-negative. While on EMI, EMI showed effectively prevented bleeding even: the median annualized bleeding rate (ABR) of 0.6 (0.0-1.9), annualized joint bleeding rate (AJBR) of 0.0 (0.0-0.3), and annualized spontaneous bleeding rate (ASBR) of 0.0 (0.0-1.59). Seven(43.8%) patients reached zero-bleeding rate (ZBR). No drug-related serious adverse events were observed. In the loading phase, patients with median age of 10.8 (5.8-32.9) months and body mass index (BMI) of 17.8 (15.6-21.6) received a median EMI loading dose of 3.0 (2.4-3.5) mg/kg. Their median EMI concentration was 65.9 (36.2-79.9) μg/mL and FVIII-like activity was 27.0 (13.5-35.4) IU/dL. Even though the mdian EMI 4-weekly maintenance dosage [4.8 (4.0-5.6)mg/kg] was below the internationally recommended dosage (6mg/kg), patients reached EMI concentration of 50.2 (36.0-76.8) μg/mL, and FVIII-like activity of 14.9 (10.4-30.4) IU/dL. EMI concentration was correlated with FVIII-like activity (rs=0.858，p＜0.001). Four (25%) patients received a total of 9 administrations of factor-based therapy. During the long-term follow-up period, the median number of exposure days (EDs) was only 0 (0-3) days. No patients tested positive for ADAs or FVIII inhibitors. Conclusion EMI has demonstrated favorable tolerability and efficacy in PUPs and MTPs with HA in infants. Using EMI at substandard doses can still achieve relatively high maintenance concentrations. Furthermore, the concentration of EMI correlates well with their FVIII-like activity. No patients developed ADAs or FVIII inhibitors.

Intercambio guiado por farmacocinética de factores VIII de vida media estándar a factores VIII de vida media extendida pegilados en la terapia de la hemofilia A en práctica clínica

ObjectiveTo analyze the differences in pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life factor VIII (FVIII) to extended half-life pegylated FVIII in patients with severe/moderate hemophilia A on prophylaxis, one year before and after the switch in real-life. MethodThis is a single-center, comparative, observational, sequential, retrospective, and multidisciplinary study. Population pharmacokinetic models from the WAPPS-Hemo® application were used to calculate pharmacokinetic parameters and individualize prophylaxis. The annual rate of total and joint bleeds, joint health (Hemophilia Joint Health Score), plasma half-life and area under the curve ratios, FVIII consumption, administration frequency, and cost were analyzed. ResultsThirty-eight adult patients with hemophilia A who switched from standard half-life FVIII to extended half-life pegylated FVIII were analyzed. Significant improvements (p < 0.05) were observed in all pharmacokinetic parameters, with plasma half-life and area under the curve improvement ratios of 1.5 and 1.9, respectively, as well as reductions in annual total and joint bleeding rates were registered. A higher number of patients with zero total (16.0 vs. 29.0) and joint bleeds (23.0 vs. 33.0) was also observed. The median reductions in administration frequency and dose/kg/week were 30.0% and 19.7%, respectively, avoiding 44.3 infusions/patient/year, resulting in savings of 20,843 €/patient/year. Furthermore, joint health improved (23.0 vs. 21.0; p = 0.017), and target joints resolved after the switch. ConclusionsThe pharmacokinetically guided switch from standard half-life FVIII to pegylated FVIII demonstrated significant clinical benefits with reduced bleeding rates and improvements in joint health. Additionally, improvements in pharmacokinetic parameters were observed, allowing for reduced treatment burden by decreasing administration frequency, as well as lower consumption and costs.

Intermediate-dose Immune Tolerance Induction Outperforms with Faster Success, Less Bleeding and No Added Cost in Comparison with Low-dose: a Multicenter Randomized Clinical Trial

BackgroundLow-dose (LD) or intermediate-dose (MD) immune tolerance induction (ITI) are effective in severe hemophilia A (SHA) children with high-titer inhibitors (HTI) and are attractive in countries with economic constraints. However, high-quality evidence for their use is lacking. ObjectivesThis is a multicenter randomized clinical trial comparing the efficacy, safety and medication cost between LD-ITI and MD-ITI for SHA-HTI children. MethodsSHA children less than 8 year-age with historical/pre-ITI inhibitor-titer 5-200 Bethesda Units/mL in 3 centers were randomized 1:1 to receive LD-ITI (recombinant [r]FVIII 50 IU/kg every-other day) or MD-ITI (rFVIII 100 IU/kg/day) from January 2022 to June 2024 (ChiCTR2200056603, https://www.chictr.org.cn.). ResultsThirty-one patients (16 in MD-ITI, 15 in LD-ITI) were enrolled and followed for more than 24 months (median 26.9, range 24.0-29.5 months). The 2 groups had similar baseline clinical characteristics and similar success rate (93.8% [MD-ITI] vs. 86.7% [LD-ITI]). Compared to LD-ITI, MD-ITI patients took shorter median time to success (4.2 months vs. 10.1 months), to partial success (2.7 months vs. 6.6 months) and had lower mean rates for all bleeding (0.38/month vs. 1.40/month) and joint bleeding (0.11/month vs. 0.83/month). Between the 2 groups, although MD-ITI group had higher rFVIII consumption (12775 vs. 7680 IU/kg), their total medication costs to success were similar (3626.49 vs. 3240.38 US$/kg). ConclusionsFor SHA-HTI children, success rate and cost for MD-ITI and LD-ITI regimens were similar. MD-ITI regimen would be a priority for regions with economic constraints considering the shorter time to success, better bleeding control, and no increase in medication cost.

Infrared thermography: An investigative tool for detection of subclinical bleed in hemophilia on prophylaxis.

Background & objectives Subclinical joint bleed is a matter of concern in individuals with hemophilia on prophylaxis. Ultrasonography (USG) is mostly used for the screening of subclinical bleeds in such individuals but it has its own limitations. Thus a more comprehensive technology is required for the detection of the same. This study undertook to evaluate the efficacy of infrared thermography (IRT) for detection of subclinical joint bleeds and its comparison with ultrasonography and MRI (Magnetic Resonance Imaging), considering MRI as the gold standard. Methods Forty eight asymptomatic individuals with hemophiliacs on prophylaxis and 15 healthy males as controls were recruited. IRT, USG and MRI were done in all participants included in the study. FLIR camera systems were used for the capture of thermograms of the joints in both the study groups. Results The mean of maximum temperature difference>0.5K (ΔT max >0.5K) as compared to a healthy joint was considered as significant. Subclinical bleeds were detected in 23.9, 7.29 and 27.08 per cent participants by IRT, USG and MRI respectively. Sensitivity and specificity of IRT and USG was detected to be 88.4 and 97.67 per cent, and 26.9 and 99 per cent, respectively. Interpretation & conclusions The findings of this study suggest that IRT is an effective tool for detection of subclinical joint bleeds in individuals with hemophilia and can be used for the monitoring of the joints in such individuals.

Real-world experience of emicizumab prophylaxis in Korean children with severe hemophilia A without inhibitors

PurposeHemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors.MethodsThis study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared.ResultsEach of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment.ConclusionThese first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Joint reaction and simulated muscle forces during squatting and walking in persons with hemophilia

BackgroundPersons with hemophilia experience joint bleeding that can lead to debilitating arthropathy, most commonly seen in ankles, knees, and elbows. Arthropathy can hinder participation in daily and athletic activities. We explored how hemophilic arthropathy impacts movement patterns in walking and bilateral squatting tasks in persons with hemophilia compared to healthy controls. MethodsPersons with hemophilia and healthy controls completed walking and squatting tasks while kinematic and kinetic motion capture data were collected. The Hemophilia Joint Health Score exam was performed to measure hemophiliac arthropathy. OpenSim was used to model muscle and joint reaction forces and calculate moments and angles. Peak values were compared using Cohen's d to estimate effect sizes of hemophilia on movement parameters. FindingsNine persons with hemophilia and eight age-matched controls were analyzed. Temporal-spatial metrics were similar between hemophilia and control groups in both tasks. In walking, persons with hemophilia had higher peak ankle dorsiflexion angles, vertical ground reaction force weight acceptance peaks, and hip extension and flexion moments compared to controls. In squatting, persons with hemophilia had lower knee extension moments, ankle joint reaction force, and knee extensor forces, but had higher hip extension moments. InterpretationTemporal-spatial metric similarity between hemophilia and controls suggests that kinetic and kinematic analyses are needed to identify movement pattern differences. These data identify potential compensatory strategies at the hip that may be used by persons with hemophilia to mitigate impact on the knee and ankle. Future work will confirm these data in a larger sample size and be used to develop physical therapy strategies.

Perioperative Pain Management in Hemophilic Patient Undergoing Orthopedic Surgery: A Narrative Review

Background: Hemophilia type A and B is associated with spontaneous bleeding in muscle tissues and joints. Acute hemarthrosis, representing 70–80% of all bleedings in severe hemophilia patients, is extremely painful. When surgical procedures are needed in hemophiliac patients, perioperative management should be planned with a multidisciplinary team. Our narrative review, through a rigorous analysis of the current literature, focuses on pain management in hemophiliac patients. Methods: The report synthesizes a literature review on hemophilia, adapting PRISMA guidelines. It identifies a research question on surgical procedures and perioperative pain management. Various sources, including electronic databases, are utilized. Study inclusion criteria are defined based on the research question. Forty studies are included. A detailed study selection is illustrated. Results: Guidelines for managing acute postoperative pain in the general population advocate for a multimodal analgesic administration to enhance synergistic benefits, reduce opioid requirements, and minimize side effects. Recent recommendations from the World Federation of Hemophilia (WFH) for postoperative pain management in hemophilia patients suggest tailoring treatment based on pain levels, in coordination with anesthesiologists. Conclusions: Pain management in hemophiliac patients undergoing orthopedic interventions requires a multidisciplinary approach, with further research needed to define a reliable global standard of treatment.

CHIEF: A retrospective self-control study of children with severe hemophilia A without inhibitors comparing emicizumab to FVIII prophylaxis.

Hemophilia A (HA) is an X-linked bleeding disorder diagnosed by a deficiency in factor VIII (FVIII). For severe HA (SHA), prophylaxis clotting factor concentrates (CFC) has become the standard of care; however, it imparts a high treatment burden and typically results in an annualized bleeding rate (ABR) of 2-6. Emicizumab, a subcutaneously administered FVIII substitute, has become the de facto standard-of-care prophylaxis for children with SHA in many countries. Previous clinical trials of emicizumab have assessed ABR in patients greater than 12years without inhibitors, and in children less than 12years with inhibitors; however, there is little information published regarding the ABR of emicizumab compared to CFC in non-inhibitor SHA children. Using a retrospective electronic medical record chart review, we conducted a self-control analysis of 15 patients less than 12years of age during equivalent periods of CFC versus emicizumab prophylaxis. The mean ABR on CFC and emicizumab was 1.79 and 1.13 (p=.092), respectively, with a substantially decreased rate of joint bleeds (CFC 0.94; emicizumab 0.33; p=.001) and spontaneous bleeds (CFC 0.79; emicizumab 0.23; p=.008). No safety events were recorded for patients while administering emicizumab. The mean annual cost of CFC prophylaxis was $515,340 (SD $199,540), compared to $328,410 (SD $137,230) for emicizumab prophylaxis (p<.001). Emicizumab resulted in an improved ABR compared to CFC, especially for joint and spontaneous bleeds, had fewer administration complications, and was substantially less expensive compared to CFC prophylaxis; however, more research is necessary for a complete understanding of the effect of emicizumab on joint health and muscle bleeds.

Utilizing artificial intelligence for the detection of hemarthrosis in hemophilia using point-of-care ultrasonography

BackgroundRecurrent hemarthrosis and resultant hemophilic arthropathy are significant causes of morbidity in persons with hemophilia despite the marked evolution of hemophilia care. Prevention, timely diagnosis, and treatment of bleeding episodes are key. However, a physical examination or a patient’s assessment of musculoskeletal pain may not accurately identify a joint bleed. This difficulty is compounded as hemophilic arthropathy progresses. ObjectivesOur system aims to utilize artificial intelligence and ultrasonography (US; point-of-care and handheld) to enable providers, and ultimately patients, to detect joint bleeds at the bedside and at home. We aimed to develop and assess the reliability of artificial intelligence algorithms in detecting and segmenting synovial recess distension (SRD; an indicator of disease activity) on US images of adult and pediatric knee, elbow, and ankle joints. MethodsA total of 12,145 joint exams, comprising 61,501 US images from 7 international healthcare centers, were collected. The dataset included healthy participants and adult and pediatric persons with hemophilia, with and without SRD. Images were manually labeled by 2 experts and used to train binary convolutional neural network classifiers and segmentation models. Metrics to evaluate performance included accuracy, sensitivity, specificity, and area under the curve. ResultsThe algorithms exhibited high performance across all joints and all cohorts. Specifically, the knee model showed an accuracy of 97%, sensitivity of 96%, specificity of 97%, and an area under the curve of 0.97 in SRD. High Dice coefficients (80%-85%) were achieved in segmentation tasks across all joints. ConclusionThis technology could assist with the early detection and management of hemarthrosis in hemophilia.

Haemophilia care in Iraq; a multi-centre study.

To evaluate the level of care available for haemophilia patients. The descriptive, retrospective analytical study was conducted from December 15, 2020, to March 1, 2021, after approval from the Mustansiriyah University, Baghdad, Iraq, and comprised data from 3 haemophilia treating centres in Iraq participating in the World Bleeding Disorders Registry. The data collected related to patients with haemophilia A and B enrolled in the registry since March 2018, and included age at diagnosis, type of haemophilia, disease severity, age at first bleed and at first joint bleed, type of replacement therapy and outcome. Data was analysed using statistical package of social sciences (SPSS) version 20. Of the 638 patients with mean age 16.2±4.3 (range: 9-29 years), 581(91%) had haemophilia A, 57(8.9%) had haemophilia B, 385(60.5%) had severe haemophilia, 126(19.8%) moderate and 125(19.7%) mild. Further, 259(41%) patients had been diagnosed for <1 year. There were 1354 bleeding events, and haemarthrosis accounted for 959(70.8%) of them. The mean annualised bleeding rate for severe patients was 2 ± 0.6(range 0-4), while the mean annualised joint bleeding rate was 4 ± 1.3(range :2-8). There were 256(32.3%) patients who were tested for inhibitors, and 62(24.3%) were positive. Among 426(73.3%) haemophilia A patients with a treatment history, 248(58%) were on prophylactic therapy, and the corresponding value among 37(65%) haemophilia B patients was 17(46%). Access to treatment was found to be limited, and patients were found to be suffering from high bleeding rates and joint damage.

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.

Emicizumab in Children with Severe Hemophilia A.

To assess the effectiveness and tolerability of emicizumab prophylaxis in hemophilia A (HA). Emicizumab is a novel therapeutic drug which is the first and only non-factor replacement agent licensed for use in people with HA. Pediatric patients aged 1 mo to 12 y with severe HA and frequent / life threatening bleeding events, with or without coagulation protein factor VIII inhibitors were enrolled (n = 18) in this observational pre-post study. Patients were switched from therapy involving on-demand or prophylactic factor VIII/bypassing agents/immune tolerance induction to emicizumab prophylaxis and followed up for 52 wk. One year before initiating emicizumab, a total of 229 bleeding events occurred among the enrolled children. After emicizumab prophylaxis, 5 patients had one episode of bleeding event each with a mean bleeding duration of 1.2 d in one year. The mean annualized bleeding rate significantly reduced from 12.7 ± 8.61 events pre-emicizumab prophylaxis to 0.28 ± 0.46 events post-emicizumab prophylaxis (p < 0.001). Out of the total cohort (n = 18), 72.2% of patients (n = 13) had no bleeding events (95% Confidence interval: 46.4-89.3) while on emicizumab. The mean annualized joint bleeding rate reduced from 9.72 ± 7.44 to 0.17 ± 0.38 (p < 0.001). The target joint resolution was 100% and no adverse events were noted. Emicizumab was found to be effective and safe as a prophylactic agent for the treatment of severe HA with and without factor VIII inhibitors. Emicizumab prophylaxis can optimize treatment outcomes and promote a better quality of life in children with severe HA.

Emicizumab revolution in treating Hemophilia

HemophiliaA (H.A.) has beenanuncommon hereditary X-linked bleeding disorder indicated by clotting factorVIII (FVIII)deficiency, leading to impaired hemostasis. H.A. affects approximately one in 5,000male births in the U.S., often resulting in spontaneous joint bleeding, chronic pain, and an increased risk of cerebral hemorrhage. Prophylactic treatment with FVIII replacement or the bispecific antibody emicizumab has become a crucial strategy to prevent bleeding episodes and long-term tissue damage. Emicizumab, approved by the FDA &amp; EMA in2018, mimics FVIII activity by binding to activated factorIX (FIXa) &amp; factorX (F.X.), facilitating blood clotting regardless of FVIII inhibitors. The development of emicizumab involved extensive bioengineering to optimize its safety, stability, and efficacy, leading to its successful application in clinical trials. These trials demonstrated that emicizumab significantly decreases the annualized bleeding rate in studied cases with or without inhibitors, including severe H.A. cases, with a favorable safety profile and minimal adverse events. Emicizumab's subcutaneous administration, high bioavailability, and predictable pharmacokinetics make it a practical option for H.A. prophylaxis. Despite its benefits, emicizumab can interfere with specific coagulation assays and may develop anti-drug antibodies (ADAs) in rare cases, potentially reducing its efficacy. Ongoing research and post-marketing surveillance continue to assess its long-term safety and effectiveness, making emicizumab a transformative treatment in managing hemophilia A.

MR Imaging of Hemosiderin Deposition in the Ankle Joints of Patients with Haemophilia: The Contribution of a Multi-Echo Gradient-Echo Sequence-Correlation with Osteochondral Changes and the Number and Chronicity of Joint Bleeds.

We aim (a) to introduce an easy-to-perform multi-echo gradient-echo sequence (mGRE) for the detection of hemosiderin deposition in the ankle joints of boys with haemophilia (b) to explore the associations between the presence and severity of hemosiderin deposition and the other components of haemophilic arthropathy, the clinical score, and the number and chronicity of joint bleeds. An MRI of 41 ankle joints of 21 haemophilic boys was performed on a 3 T MRI system using an mGRE sequence in addition to the conventional protocol. Conventional MRI and mGRE were separately and independently assessed by three readers, namely, two musculoskeletal radiologists and a general radiologist for joint hemosiderin. We set as a reference the consensus reading of the two musculoskeletal radiologists, who also evaluated the presence of synovial thickening, effusion, and osteochondral changes. Excellent inter-reader agreement was obtained using the mGRE sequence compared to the conventional protocol (ICC: 0.95-0.97 versus 0.48-0.89), with superior sensitivity (90-95% versus 50-85%), specificity (95.2-100% versus 76.2-95.2%), and positive (95-100% versus 71-94.4%) and negative predictive value (91.3-95.5% versus 87-63%). Hemosiderin deposition was associated with osteochondral changes, synovial thickening, clinical score, and the total number of ankle bleeds, while it was inversely related with the time elapsed between the last joint bleed and MRI. (p < 0.05). The application of an mGRE sequence significantly improved hemosiderin detection, even when performed by the less experienced reader. Joint hemosiderin deposition was associated with the other components of haemophilic arthropathy and was mostly apparent in recent joint bleeds.

Clinical, Demographic, And Haematological Profile of Haemophilia Patients at Sir Sunder Lal Hospital Varanasi With CoE Haemoglobinopathies And Day Care Centre

Introduction: Hemophilia is a recessive coagulation and bleeding disorder that is X-linked and inheritable. The Factor VIII (F8) and Factor IX (F9) genes are involved in hemophilia A and B, two hereditary diseases. The process of hemostasis is hampered by spontaneous or post-traumatic bleeding, which also increases the risk of hemophilia. Aim: The purpose of our study is to evaluate the hematological, clinical, and demographic traits of individuals with hemophilia A and B. Results: A total of 646 hemophilia patients were examined during the study period. the majority of hemophilia A patient 544 (84.21%) and hemophilia B102 (16.01%). Based on severity, severe 342 (52.94%), Moderate 247 (38.24%), and Mild (8.82%) had been diagnosed Most common age group was &lt;1 -58 years. The bulk of the study population had a mean age of (Mean ±SD=18.45±13.00) and a median of 17. Maximum number of patients at the ages of 21 and 30 years (21.05%) and a median of 25. The most common age of spontaneous bleeding across all patients was 17 and there was no discernible difference between those with moderate and severe symptoms of bleeding. Hemarthrosis infection (target joint) was most prevalent (79.10%), then prolonged bleeding after cut/ trauma (62.38%). Hemarthrosis knee joint was the joint that was infected (target joint) the most common (79.10%), followed by joint bleeding (46.75%) Severe disease affected the knee joint more frequently than moderate disease. Conclusion: The present research revealed differences in the incidence and nature of bleeding on its own in hemophilia patients. Gum bleeding and posttraumatic bleeding in a child who is otherwise healthy should alert the doctor to consider hemophilia onset is &lt;1 year. On the other hand, 61.3% of patients had hemophilia when they received their initial diagnosis. The median number of bouts of

Importance of physical activity in the treatment of hemophilia

Hemophilia is a genetically determined bleeding disorder characterized by a tendency for spontaneous bleeding, mainly into the joints, which can lead to arthropathy and significantly reduce the quality of a patient's life. The objective of this paper is to review the published literature on the impact of physical activity on the course of the disease and its role in current therapeutic protocols. Online databases were used to search for literature. The retrieved articles were analyzed. The review mainly included literature published after 2016. In the past, physical exercise was not recommended for people with hemophilia, primarily due to concerns about joint bleeding and the development of hemophilic arthropathy. Currently, regular, moderate physical activity plays a crucial role in the management of hemophilia, helping to strengthen muscles and improve joint stability, which can reduce the risk of bleeding. This shift in perspective is largely due to the availability of effective therapeutic options, mainly involving the replacement clotting factors. However, entirely new hopes for a permanent cure and the maintenance of physical fitness are brought by modern gene therapy treatments. Physical activity is essential for maintaining the health and fitness of individuals with hemophilia, and most exercises are safe due to effective prophylactic treatment. In addition to the benefits for joint health, regular exercise also helps prevent many lifestyle-related diseases.