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This article discusses the relevance of magnetic resonance imaging (MRI) findings in individuals with haemophilia. It highlights that most bleeding episodes in haemophilia occur in the large synovial joints, leading to irreversible haemophilic arthropathy. The article emphasizes the importance of detecting subclinical bleeding and inflammation, as they contribute to the development of arthropathy. MRI is considered the gold standard for evaluating early blood-induced joint changes in haemophilia, and the International Prophylaxis Study Group (IPSG) has developed a comprehensive scoring scheme for MRI assessment. The article also discusses the clinical consequences of subclinical bleeding, the evaluation of joint effusions, and the assessment of osteochondral abnormalities using MRI. It concludes by stating that MRI provides a complete overview of joint status in individuals with haemophilia and that the IPSG MRI Scale version 2.0 facilitates standardized MRI scoring for future outcome studies. [Extracted from the article]

Aim: Haemophilia is characterized by recurrent joint bleeding caused by a lack of clotting factor VIII or IX. Due to repeated joint bleeding, end‐stage arthropathy occurs in relatively young patients. A total knee replacement (TKR) can be a solution. However, TKR may be complicated by perioperative and postoperative bleeds despite clotting factor therapy. The aim of this study was to evaluate the prevalence of pre‐operative synovial hyperaemia and the effects of Genicular Artery Embolization on synovial hyperaemia and 3‐month postoperative joint bleeding. Methods: In this retrospective cohort study, all patients with haemophilia who underwent periarticular catheter angiography between 2009 and 2020 were evaluated after written informed consent. Synovial hyperaemia on angiography was scored by an interventional radiologist. Results: Thirty‐three angiography procedures in 24 patients were evaluated. Median age was 54.4 years (IQR 48.4–65.9). Preoperative synovial hyperaemia was observed in 21/33 joints (64%). Moderate and severe synovial hyperaemia was observed in 10/33 joints (30%). Synovial hyperaemia decreased in 13/15 (87%) joints after embolization. Three‐month postoperative joint bleeding occurred in 5/32 joints: in 2/18 joints (11%) without synovial hyperaemia and in 3/14 joints (21%) with mild synovial hypertrophy. Non‐embolized and embolized joints did not differ regarding 3‐month postoperative bleeding (P =.425). No complications were observed after embolization. Conclusion: One‐third of patients with haemophilia requiring a TKR had moderate or severe synovial hyperaemia which can be reduced safely by Genicular Artery Embolization prior to TKR. Three‐month postoperative bleeding appears to occur independently of the presence of residual mild synovial hyperaemia. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of prophylaxis with rIX‐FP, a fusion protein linking recombinant factor IX (FIX) with human albumin, on joint outcomes. Methods: Joint outcomes were assessed in pediatric (<12 years) and adult/adolescent (≥12 years) patients receiving rIX‐FP prophylaxis every 7, 10, or 14 days; patients (>18 years) well‐controlled on a 14‐day regimen could switch to a 21‐day regimen. Target joints were defined as ≥3 spontaneous bleeds into a single joint within a 6‐month period. Results: For adult/adolescent (n = 63) and pediatric (n = 27) patients, median (Q1, Q3) annualized joint bleeding rate was 0.39 (0.00, 2.31), 0.80 (0.00, 2.85), 0.20 (0.00, 2.58), and 0.00 (0.00, 1.78) when treated with 7‐, 10‐, 14‐, or 21‐day prophylaxis. 50.0%, 38.9%, 45.5%, and 63.6% of adult/adolescent patients had no joint bleeds when treated with 7‐, 10‐, 14‐, or 21‐day prophylaxis, respectively, and 40.7%, 37.5%, and 37.5% of pediatric patients had no joint bleeds when treated with 7‐, 10‐, or 14‐day prophylaxis. Ten adult and two pediatric patients developed target joints; all resolved by the end of the study. Conclusion: Prophylaxis with rIX‐FP produced low joint bleeding rates and provided excellent hemostatic efficacy in the treatment of joint bleeds. All target joints reported resolved with rIX‐FP prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction: In chronic diseases, disease‐related distress can impact disease outcomes. Distress and haemophilia‐related distress has been demonstrated in people with haemophilia (PwH). The association of haemophilia‐related distress on disease outcomes among PwH is unknown. Aim: To study the association of haemophilia‐related distress with haemophilia specific outcomes, including adherence to prophylactic therapy, the presence of a target joint, healthcare utilization and work‐impairment. Methods: In a cross‐sectional study, adults with haemophilia A or B were enrolled in a study to validate the haemophilia‐related distress questionnaire (HRDq). In this planned analysis, univariate and multivariate associations between the HRDq total score and disease outcomes were explored. Results: The 114 participants in this analysis were male, mostly with haemophilia A (92%) and severe disease (52%) with a median age of 31.9 years. On univariate analysis, HRDq total score (5‐point change) was associated with the presence of a target joint (P =.002), high healthcare utilization (P =.011), poor adherence (P =.033) and work‐impairment (P ≤.001). After adjustment for age, race, severity and other potential confounders, adherence (aβ 0.33, 95% CI.17,.49) and work‐impairment (aβ 4.69, 95% CI 3.27‐6.1) remained statistically significantly associated with HRDq total score. Conclusion: Haemophilia‐related distress is associated with poor adherence to factor prophylaxis and work‐impairment. The direction of the association (causation) is yet to be determined and requires future study. [ABSTRACT FROM AUTHOR]

Background: Teleguidance on portable devices opens the possibility of joint self‐imaging in persons with hemophilia (PWH). Aims: Determine the feasibility of patient self‐imaging with/without teleguidance. Methods: Adult PWH received ultrasound teaching including 11 views for hemarthrosis detection in ankles, elbows, and knees. The patients acquired five randomly selected views with the Butterfly/IQ probe without assistance at 2, 6–8 weeks, and 3–4 months later, followed by teleguidance. Image acquisition was timed, patients identified anatomic landmarks, and image quality was graded. Questionnaires assessed the imaging experience. Hemophilia Joint Health Score (HJHS) indicated arthropathy status. Results: Of 132 PWH, 10 (median age 52 years) opted for study inclusion. Most had severe Hemophilia A, were white/non‐Hispanic, with at least a high school degree and, overall, similar to the other 122 PWH. At 2 and 6 weeks after training, ~80% images were acquired correctly compared with 53% at 12 weeks. Accuracy of landmark recognition was ~55%. With teleguidance, all images were acquired correctly, with near‐perfect image quality (P ≤.01 compared with the 3–4 month time point). Median HJHS of scanned joints was 11.5 at each time point, demonstrating a similar spectrum of arthropathic changes. Median time of image acquisition was fast, and similar with or without teleguidance (median 01:04 [mm:ss] vs median 01:02), but differed slightly between arthropathic and non‐arthropathic joints. Study participants and the imaging facilitator rated that it was easy to navigate mobile technology and acquire images with teleguidance. Conclusion: Mobile ultrasound with teleguidance for joint self‐imaging is feasible and warrants further exploration. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia patients experience painful joint episodes which may or may not be associated with haemarthrosis. We sought to validate a questionnaire developed by the Canadian Haemophilia Society using point‐of‐care musculoskeletal ultrasound (POC MSKUS) to confirm haemarthrosis. Methods: The questionnaire comprised of 20 questions (10 each associated with haemarthrosis and arthritis pain) and was administered to adult haemophilia patients reporting to the Haemophilia Treatment Centre (University of California San Diego). We confirmed the presence (or absence) of haemarthrosis using POC MSKUS [Joint Activity and Damage Exam (JADE)]. We fitted univariate and multivariate generalized estimating equations to identify symptoms associated with haemarthrosis. Results: We evaluated 79 painful episodes in 32 patients [median age = 38 years (range 21–74)]. POC MSKUS detected haemarthrosis in 36 (46%) episodes. The strongest predictor for haemarthrosis pain was 'like a balloon swelling with water' (odds ratio [OR] 2.88 [CI.68;12.10]); 'no feeling of sponginess with movement' (OR.24[CI.07;.76]) was the strongest for arthritic pain. We identified four questions with the strongest OR for differentiating haemarthrosis pain from arthritic pain to develop an algorithm for haemarthrosis prediction. Answering these questions in "yes/no" fashion yielded estimates of the probability of haemarthrosis Conclusion: Objective diagnosis of haemarthrosis by MSKUS facilitated the development of a symptom‐based prediction tool for diagnosis of haemarthrosis. The tool requires further validation and will be particularly helpful in situations where MSKUS is not readily available. [ABSTRACT FROM AUTHOR]

Introduction: Women and girls affected by haemophilia, including haemophilia carriers (WGH) are at risk of bleeding symptoms that may go unrecognized, including heavy menstrual bleeding (HMB) and musculoskeletal bleeding. Terminology continues to evolve. Aim: To describe the current recommendations for nomenclature surrounding WGH, and the current understanding of HMB, iron deficiency, and musculoskeletal complaints in these patients. Methods: Literature was reviewed and summarized. Results: With regards to nomenclature, women with factor levels less than 50% should be classified as having haemophilia, while carriers with normal levels should be characterized accordingly to symptomatology. HMB and resultant iron deficiency are common among WGH, have a multitude of downstream effects, and maybe overlooked due to stigma around menstruation. Musculoskeletal bleeding and resultant joint changes are increasingly recognized in this population but do not necessarily correlate with factor levels. Conclusion: Although progress has been made in the care of WGH, much work remains to further improve their care. [ABSTRACT FROM AUTHOR]

A female was diagnosed with hemophilia A. She had undergone bilateral total knee arthroplasty. She had a history of numerous hemorrhages including hemarthrosis. After further investigations, the diagnosis of von Willebrand disease type 2N was confirmed. The differential diagnoses for hemophilia A include von Willebrand disease, rare bleeding disorders, and severe platelet disorders. [ABSTRACT FROM AUTHOR]

Introduction: Joint damage in haemophilia often requires surgical correction. However, the surgery effect on bleeding rates and other clinical joint outcomes can be unclear. Aim: To investigate the effects of joint surgery on joint annualized bleeding rates (JABRs) and physical health outcomes in patients with haemophilia A undergoing N8‐GP prophylaxis. Methods: Patients in the pathfinder 2 trial received N8‐GP prophylaxis, enrolling in the pathfinder 3 trial for indicated surgery. Patients returned to pathfinder 2 post‐surgery, continuing N8‐GP prophylaxis until end‐of‐trial. JABRs were calculated from bleeding across all joints for pre‐surgery (immediately before surgery) and post‐surgery (to pathfinder 2 study end) periods. Joint‐health‐related outcomes were derived from patient records. Results: Data (41 joint surgeries; n = 30) were analysed statistically using datamining and descriptively. Pre‐surgery mean JABR was higher in patients who later were operated than in 146 non‐operated patients (p =.004). In operated patients, mean JABR decreased from 1.33 pre‐surgery to.37 post‐surgery (p =.011). In all but three patients, JABR improved or remained the same post‐surgery. In the three patients whose JABR remained at one (all with multiple joint arthropathy), post‐surgery bleeds were mostly at non‐operated sites. Two of the three patients whose JABR increased post‐surgery had undergone surgery for reasons unlikely to improve JABR. Mobility parameters often improved in patients whose JABR remained at zero. Conclusion: Patients with haemophilia treated with N8‐GP prophylaxis benefit from surgeries. However, this analysis could not differentiate the relative contributions of surgical interventions and prophylactic treatment to the improvement of JABR. [ABSTRACT FROM AUTHOR]

Background: Painful arthropathy is a long‐term complication in patients with hemophilia (PWH), affecting mobility and quality of life. A major barrier for the appraisal of joint health is the absence of point‐of‐care (POC) imaging modalities to promptly identify and manage arthropathic changes. Accordingly, we developed the Joint tissue Activity and Damage Exam (JADE) POC musculoskeletal ultrasound (MSKUS) protocol. JADE is validated for haemophilic joint tissue recognition with high intra/inter‐rater and inter‐operator reliability. Aims: Evaluate associations of JADE with clinical (Hemophilia Joint Health Score, [HJHS]) and functional (total arc [combined flexion and extension range of motion [ROM]]) parameters. Methodology: In this multi‐centre prospective study, we recruited PWH A or B with at least one arthropathic joint. We evaluated joint health (both elbows, knees, and ankles) by comparing JADE measurements (soft tissue and cartilage thickness, and osteochondral alterations) with HJHS and total arc. Results: Of 44 PWH, most had hemophilia A (35/44), were severe (36/44) and had a median age of 36 years. Increasing HJHSs and declining total arc, indicating worsening arthropathy, were associated with JADE measurements in the expected direction, including (1) increasing length of osteochondral alterations, (2) diminished cartilage thickness, and (3) greater soft tissue expansion. The ankles had the highest proportion of joints without measurable (missing) cartilage. In multivariable models MSKUS measurements explained 68% and 71% of the variation in HJHS and total arc respectively for the elbow, 55% and 29% respectively for the knee, and 50% and 73% for the ankle. Conclusions: This study highlights the associations of direct intra‐articular ultrasonography measurements using the JADE protocol with clinical and functional parameters. Our findings underscore the clinical value of POC MSKUS using the JADE protocol as a complementary instrument for the diagnosis and management of haemophilic arthropathy. [ABSTRACT FROM AUTHOR]

Introduction: Early intervention in the devastating process of haemophilic arthropathy (HA) is highly desirable, but no disease‐modifying therapy is currently available. Considering the pivotal role of iron in the development of HA, iron chelation is considered a promising therapeutic approach. A previous study in haemophilic mice demonstrated that treatment with the iron chelator deferasirox (DFX) 8 weeks before joint bleed induction, attenuated cartilage damage upon blood exposure. However, in haemophilia patients this approach is not opportune given the unpredictable occurrence of hemarthroses. Aim: To evaluate the effectiveness of on‐demand DFX treatment, initiated immediately after joint bleed induction. Methods: A joint bleed was induced in 66 factor VIII‐deficient mice by infra‐patellar needle puncture. Mice were randomly assigned to treatment with either placebo (drinking water) or DFX (dissolved in drinking water) throughout the study. Five weeks after joint bleed induction, inflammation and cartilage damage were assessed histologically. Joints of ten bleed naive haemophilic mice served as controls. Results: A joint bleed resulted in significant inflammation and cartilage damage in the blood‐exposed joint compared with those of control animals, in both the placebo and DFX group (all p = <.05). No differences in tibiofemoral or patellar inflammation (p =.305 and p =.787, respectively) nor cartilage damage (p =.265 and p =.802, respectively) were found between the blood‐exposed joints of both treatment groups. Conclusion: On‐demand treatment with DFX does not prevent joint damage following blood exposure in haemophilic mice. DFX seems unable to reach the joint in time to exert its effect before the irreversible harmful process is initiated. [ABSTRACT FROM AUTHOR]

Introduction: Sports participation in children with hemophilia is generally considered to be associated with increased injury risk, which is generally considered highest in severe hemophilia. Aim: To assess sports participation according to age and severity in children with hemophilia and its association with sports injuries. Methods: In a retrospective single‐center study, sports participation, injuries, and bleeding data from three consecutive annual clinic visits were collected for young patients with hemophilia (PWH, aged 6‐18). Sports in categories 2.5 and 3 of 3 according to the National Hemophilia Foundation classification were considered high‐risk. Groups were compared using chi‐square testing. Results: 105 PWH (median age: 13(IQR 10‐14); 53% severe; bleeding rate: 1/y) were identified; three were unable to perform sports and were excluded. The majority of PWH (77%) played sports weekly, of which 80% high‐risk sports. Sports participation (median 3.0x/wk), and the proportion of injured PWH was similar in severe (42%) and non‐severe (33%) PWH. Sports injuries were rare (65% no injuries in 3 years, median 0/y (IQR 0‐1)). Annually, PWH did not report more injuries (15%) than age‐matched boys (28%). Sports injuries were not associated with frequency and type of sports. Discussion: This retrospective study showed high sports participation (including high‐risk sports) and low injury rates. Sports participation was similar across severities and injury rates were not higher than among the general population. Injuries were not associated with frequency or type of sports. A prospective study with objective assessment of sports participation and injuries is warranted to confirm these findings and avoid recall bias. [ABSTRACT FROM AUTHOR]

Introduction: The benefits of physical activity (PA) for people with haemophilia (PWH) may include improvements in joint, bone and muscle health. However, the factor VIII activity level required to avoid a bleeding episode associated with PA is unknown. Aim: To elicit the opinion of clinical experts on the minimum level and ideal factor VIII activity ('level') required to avoid a bleeding episode during participation in different types of PA for PWH. Methods: Based on the 2017 National Hemophilia Foundation PA descriptions, clinical experts estimated a minimally acceptable and an ideal factor level at which a bleed could be avoided. The uncertainty around estimates was quantified using an approach to construct a probability distribution to represent expert opinion. Results: Minimum and ideal factor level increased with higher risk PA, whether or not joint morbidity was present, as did the experts' uncertainty in their estimates (ie the range between lowest and highest estimates for minimum and ideal levels). Mean minimum levels ranged from 4% to 48% for low to high risk for people without joint morbidity, and from 7% to 47% for those with joint morbidity. For ideal factor levels, corresponding figures were 9%‐52% and 12%‐64%, respectively. Conclusion: To support a patient‐centric outcome, expert opinion indicates that the clinical norm of 0.01 IU/mL (1%) trough level is insufficient. It is anticipated that introducing a more targeted approach to meet the needs of patients who are increasingly physically active will benefit patients further in addition to recent treatment advances. [ABSTRACT FROM AUTHOR]

Introduction: Radiocolloids labelled with less costly and more accessible radionuclides such as rhenium‐188 are of interest to developing countries compared with those labelled with rhenium‐186 and yttrium‐90. Aim: This study was aimed to evaluate the efficacy and safety of radiosynovectomy using rhenium‐188 in patients with chronic haemophilic synovitis and recurrent hemarthrosis. Methods: In this quasi‐experimental prospective study, 20 haemophilic patients were evaluated at preinjection, and at 1, 3, 6 and 12 months after injection. Magnetic resonance imaging (MRI) was done to measure synovial thickness and to calculate Denver score. Joint radiographs were taken to measure the Pettersson score. The Gilbert questionnaire, Functional Independence Score in Hemophilia (FISH) and visual analogue scale (VAS) for pain were completed, and the number of bleeding episodes and factor consumption were recorded at each follow‐up visit. Results: The number of bleeding episodes, the amount of factor consumption per month, VAS pain scores and synovial thickness decreased significantly over time (P <.05). Gilbert and FISH scores showed significant improvement (P <.001). However, Pettersson score and Denver score showed no significant changes after injection. Minor complications including temporary pain and swelling occurred in 20% of patients, and no major complication was observed after rhenium‐188 injection. Conclusion: Our results indicated high clinical impact, efficacy, safety and low invasion of rhenium‐188 in radiosynovectomy of haemophilic patients. Considering the availability and relatively low cost of rhenium‐188 in developing countries, this can be a good treatment option for haemophilic patients with recurrent hemarthrosis, particularly when the synovial hypertrophy is not massive yet. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament reconstructive surgery can restore biomechanical stability, however, such surgery cannot reliably prevent the onset of post‐traumatic osteoarthritis. The aim of this study was to elucidate the molecular response that occurs within the menisci following a surgical injury that allows bleeding into the joint space, and then to investigate the effect of dexamethasone (DEX) on this molecular response. Cell viability studies following acute controlled exposure to blood and blood plus DEX were also conducted. Forty‐eight New Zealand white rabbits were randomly allocated into control, sham, surgical, and surgical  + DEX groups (each group n  =  6). Animals were sacrificed at 48 h and 9 weeks, and menisci were harvested. The messenger RNA (mRNA) expression levels for key inflammatory, and degradative proteins, as well as mRNA levels for autophagy pathway molecules were quantified, and statistically significant changes were described. Meniscal cell viability was calculated by incubating groups of medial and lateral menisci in autologous blood, or autologous blood plus DEX for 48 h (each group n  =  4; total of eight medial and eight lateral menisci), and then conducting a histological live/dead assay. Results indicated a significant reduction in only medial meniscal cell viability when the tissue was exposed to blood in combination with DEX. A single administration of DEX following surgery significantly suppresses the elevated molecular expression for key inflammatory and degradative markers within menisci at 48 h and 9 weeks post‐surgery. In vitro, autologous blood did not affect cell viability, but addition of DEX uniquely impacted the medial menisci. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2043–2052, 2019 [ABSTRACT FROM AUTHOR]

Summary: A 3‐day‐old Standardbred filly, born from a multiparous mare, was presented for assessment of limb swellings and reduced appetite. Physical examination revealed tachycardia, multifocal petechial and ecchymotic haemorrhages, stiff gait, polysynovial effusion, as well as erosions, multifocal crusting and erythema of the skin. Laboratory examinations revealed adequate transfer of passive immunity, marked thrombocytopenia, moderate neutropenia and anaemia. Aerobic bacterial blood culture was negative. Sanguineous fluid, consistent with haemarthrosis, was obtained by synoviocentesis. The foal was successfully managed with the administration of blood transfusions, an immunosuppressive regimen of corticosteroid medication, systemic antimicrobial medication and supportive care and recovered uneventfully. This report describes a neonatal foal with marked thrombocytopenia and signs of coagulopathy, neutropenia and ulcerative dermatitis consistent with a previously described syndrome. This case emphasises that alloimmune disease should be considered in neonatal foals with haemostatic disturbances or unexplained cytopenia. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent joint bleeding is the hallmark of haemophilia. Synovial hypertrophy observed with Magnetic Resonance Imaging (MRI) is associated with an increased risk of future joint bleeding. Aim: The aim of this study was to investigate whether point‐of‐care ultrasound (POC‐US) is an accurate alternative for MRI for the detection of early joint changes. Methods: In this single centre diagnostic accuracy study, bilateral knees and ankles of haemophilia patients with no or minimal arthropathy on X‐rays were scanned using POC‐US and 3 Tesla MRI. POC‐US was performed by 1 medical doctor, blinded for MRI, according to the "Haemophilia Early Arthropathy Detection with Ultrasound" (HEAD‐US) protocol. MRIs were independently scored by 2 radiologists, blinded for clinical data and ultrasound results. Diagnostic accuracy parameters were calculated with 95% confidence intervals (CI). Results: Knees and ankles of 24 haemophilia patients (96 joints), aged 18‐34, were studied. Synovial hypertrophy on MRI was observed in 20% of joints. POC‐US for synovial tissue was correct (overall accuracy) in 97% (CI: 91‐99) with a positive predictive value of 94% (CI: 73‐100) and a negative predictive value of 97% (CI: 91‐100). The overall accuracy of POC‐US for cartilage abnormalities was 91% (CI: 83‐96) and for bone surface irregularities 97% (CI: 91‐99). Conclusion: POC‐US could accurately assess synovial hypertrophy, bone surface irregularities and cartilage abnormalities in haemophilia patients with limited joint disease. As POC‐US is an accurate and available alternative for MRI, it can be used for routine evaluation of early joint changes. [ABSTRACT FROM AUTHOR]

Objectives: Patients with severe haemophilia A (HA) receive factor VIII (FVIII) replacement therapy as prophylaxis. myPKFiT®is an online medical application that allows authorized users to simulate dosing regimens with patient pharmacokinetic (PK) profiles based on only 2 blood samples. Our aim was to assess the impact of using this medical device in routine practice in terms of FVIII consumption and clinical outcomes. Methods: Thirty‐six patients with severe HA on prophylaxis with Advate® were recruited in 3 centres in Spain. Annual bleeding rate (ABR), annual joint bleeding rate (AJBR) and annual FVIII consumption before and after adjustment were obtained using the patient’s clinical history (12 months before) and prospectively recorded data (12 months after), respectively. Adjustment was based on PK parameters provided by myPKFiT®, joint status and relative risk associated with physical activity and bleeding phenotype. Results: ABR and AJBR were significantly reduced after adjustment in the overall sample (−2.2 ± 1.3, P = .018 and −1.9 ± 1.2, P = .012, respectively) and in patients aged >15 years (−2.6 ± 1.4, P = .011 and −2.0 ± 1.2, P = .005, respectively). Adjustment had an effect on the individual FVIII consumption of most patients: annual amount was reduced in 18 cases and increased in 14. There was no significant effect on the mean amount (198 784 ± 110 387) compared to that used the year prior to myPKFiT®‐adjusted prophylaxis (199 466 ± 103 670; P = .737). Discussion: Our results suggest that PK‐guided prophylaxis using myPKFiT® improved clinical outcomes and optimized FVIII consumption in the study population. This personalized approach may reduce bleeding rates without significantly increasing the overall cost of FVIII therapy. [ABSTRACT FROM AUTHOR]

Objectives: Patients with severe haemophilia A (HA) receive factor VIII (FVIII) replacement therapy as prophylaxis. myPKFiT®is an online medical application that allows authorized users to simulate dosing regimens with patient pharmacokinetic (PK) profiles based on only 2 blood samples. Our aim was to assess the impact of using this medical device in routine practice in terms of FVIII consumption and clinical outcomes. Methods: Thirty‐six patients with severe HA on prophylaxis with Advate® were recruited in 3 centres in Spain. Annual bleeding rate (ABR), annual joint bleeding rate (AJBR) and annual FVIII consumption before and after adjustment were obtained using the patient’s clinical history (12 months before) and prospectively recorded data (12 months after), respectively. Adjustment was based on PK parameters provided by myPKFiT®, joint status and relative risk associated with physical activity and bleeding phenotype. Results: ABR and AJBR were significantly reduced after adjustment in the overall sample (−2.2 ± 1.3, P = .018 and −1.9 ± 1.2, P = .012, respectively) and in patients aged >15 years (−2.6 ± 1.4, P = .011 and −2.0 ± 1.2, P = .005, respectively). Adjustment had an effect on the individual FVIII consumption of most patients: annual amount was reduced in 18 cases and increased in 14. There was no significant effect on the mean amount (198 784 ± 110 387) compared to that used the year prior to myPKFiT®‐adjusted prophylaxis (199 466 ± 103 670; P = .737). Discussion: Our results suggest that PK‐guided prophylaxis using myPKFiT® improved clinical outcomes and optimized FVIII consumption in the study population. This personalized approach may reduce bleeding rates without significantly increasing the overall cost of FVIII therapy. [ABSTRACT FROM AUTHOR]

Background: The recommended treatment in patients with severe haemophilia is prophylaxis. This prevents bleedings and reduces or delays the haemophilic arthropathy. Adherence defined as the follow‐up of the patient to the prescriptions of the health professional to his treatment, both pharmacological and modifications in habits or stylelifes. Adherence rates in haemophilia are better than in other chronic diseases, but there remain reasons for nonadherence. The aim was to see if disease behaviour and disease perception together with coping strategies modulate adherence to treatment. Material and Methods: Multicenter cross‐sectional descriptive study. Patients recruited in Units of Hemophilia Hospitals and Regional Haemophilia Associations. Twenty‐three patients participated The instruments used are as follows: data sheet, SF‐36, A36 Hemophilia‐Qol, Illness Perception Questionnaire‐Revised (IPQ‐R), Illness Behavior Questionnaire (IBQ) and Coping Strategies Inventory (CSI) and VERITAS‐Pro. Results: We found that 56% of patients with haemophilia are adherent. The most relevant clinical variables were hemarthrosis, diagnosis of arthropathy and presence of any coinfection, as well as family history, labour status and sociodemographic variables. Age was not a relevant variable in adherence. The worst adherence coincides with poorer quality of life and inadequate coping style. Nonadherent patients show greater conviction of disease, perception of cyclicity, more hypochondriacal behaviour towards the illness and perception concern about possible side effects of medication. Conclusion: Adherence in haemophilia requires a more experiential approach and individualized education. It is important that professionals take into account the patient's perception, behaviour and attitude towards the disease to achieve a better adaptation of their coping resources. [ABSTRACT FROM AUTHOR]

Introduction: Improvements in the medical management for those with haemophilia have resulted in improved clinical outcomes. However, current treatment regimens do not alleviate all joint haemarthroses with the potential for long‐term joint deterioration remaining. The evaluation of functional activities such as gait, using standardized tools to monitor children with haemophilia is emerging. Aim: This study explored differences in sagittal plane biomechanics of walking in adolescent boys aged 11‐18 years with haemophilia and an age‐matched group of typically developing boys. Methods: A motion capture system and 2 force platforms were used to collect sagittal plane kinematic, kinetic and temporal spatial data during level walking. Principal component analysis (PCA) was applied to kinematic and kinetic waveform variables. Group differences in temporal spatial and principal component scores for each kinematic and kinetic variable were evaluated using independent t tests. Results: Significant alterations (P < .05) in temporal spatial and kinetic parameters were found in adolescent boys with haemophilia. Compared with typically developing adolescent boys, boys with haemophilia walked with reduced stance phase duration and altered pattern of external ankle joint moments during push off and the beginning of swing. Conclusion: The use of PCA rather than predetermined discriminatory variables provided additional insight into biomechanical alterations in adolescent boys with haemophilia, with adaptations occurring during terminal double support and early swing, affecting the ankle joint. This finding might be a key biomechanical marker that could be used to evaluate the joint function and the progression of early haemophilic arthropathy. [ABSTRACT FROM AUTHOR]

Introduction There has been increasing recognition in recent years that female carriers of haemophilia manifest abnormal bleeding; however, data on the use of bleeding assessment tools in this population are lacking. Aim Our objective was to validate the ISTH- BAT in haemophilia carriers to describe bleeding symptoms and allow for comparisons with factor levels and other patient groups. Methods This was a prospective, observational, cross-sectional study performed by members of Global Emerging HEmostasis Panel ( GEHEP). Unselected consecutive haemophilia carriers were recruited and a CRF and the ISTH- BAT were completed by study personnel. Results A total of 168 haemophilia carriers were enrolled: 155 haemophilia A and 13 haemophilia B. The mean age was 40 years (range: 20-82). Carriers had higher mean bleeding scores ( BS) compared with age-matched controls ( n = 46; 5.7 vs. 1.43; P < 0.0001) and Type 3 VWD OC ( n = 32; 3.0; P = 0.009), but lower BS compared with women with Type 1 VWD ( n = 83; 8.7; P < 0.0001). Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/ FIX levels. There was a significant but weak negative correlation between BS and factor level (Spearman's r2 = −0.36, P < 0.001). Conclusion Our results show that haemophilia carriers experience abnormal bleeding, including haemarthrosis. Overall, BS in women with Type 1 VWD > haemophilia carriers > Type 3 VWD OC > controls. Understanding the performance of the ISTH- BAT in this population is a critical step in future research aimed at investigating the underlying pathophysiology of abnormal bleeding, with the ultimate goal of optimizing treatment. [ABSTRACT FROM AUTHOR]

Background The aim of replacement therapy in haemophilia is to improve Health-Related Quality of Life (HRQoL) by preventing bleeding and arthropathy. However, the association of arthropathy with HRQoL is unknown. Aim To explore the association of haemophilic arthropathy with HRQoL. Methods A post hoc analysis on patients with severe/moderate haemophilia with SF36 questionnaire (SF36) and X-rays of ankles, knees and elbows made within 2.5-years. The SF36 scores of 'physical functioning' (SF36-PF, range 0-100, optimum 100) and Utility (SF6D-Utility, range 0-1, optimum 1) and radiological Pettersson scores (PS, range 0-78, optimum 0) were calculated. The association of PS with reduced SF6D-Utility and SF36-PF ( 21 points, the risk of reduced SF6D-Utility was stable (OR 4.16; 95% CI: 2.03-8.51) but SF36-PF continued to decrease: compared to lowest PS, OR for reduced SF36-PF was 5.69 (95% CI: 1.62-20.06) for PS 22-39 and 25.15 (95% CI: 6.53-96.81) for PS 40-78. Conclusion Health-Related Quality of Life only showed a significant deterioration in patients with a Pettersson score of >21 points. This suggests that HRQoL is relatively insensitive to early joint changes. [ABSTRACT FROM AUTHOR]

Introduction The prophylactic administration of clotting factor concentrate is currently the most effective strategy for the prevention of joint bleeding. As new agents with different mechanisms of action and administration schedules are developed, it will be important to study them in relevant preclinical models. Aim The aim of this study was the standardization of a mouse haemarthrosis model in a haemophilia mouse and the development and validation of a comprehensive bleeding assessment system, the Bleeding Severity Score ( BSS). Methods and Results Four outcome measurements were assessed, two of which, the extra-articular bleeding score and intra-articular bleeding score, were determined to be the most reliable and were summarized into a BSS which was validated using a mouse haemarthrosis variability model. Conclusion Using this model, the haemostatic effect of prospective drugs can be assessed in a clinically relevant joint bleeding model and will significantly increase the value of preclinical studies. [ABSTRACT FROM AUTHOR]

Blue rubber bleb nevus syndrome (BRBNS) involves cutaneous vascular malformation characterized by multiple venous malformations. This commonly affects the skin and gastrointestinal tract. BRBNS is associated with anemia and occasionally involves orthopedic manifestations. A 6-year-old boy was referred to hospital for evaluation of anemia. He presented with a rubber-like soft-tissue mass in the left knee and the right side of the neck, recurrent pain, and fixed flexion contracture of the knee. Blood examination indicated consumption coagulopathy and anemia caused by not only iron-deficiency anemia but also microangiopathy. Endoscopy of the gastrointestinal tract indicated multiple bluish-black sessile venous malformations. Ultrasonography and magnetic resonance imaging of the knee showed intra-articular and intramuscular involvement. Based on these findings, BRBNS with knee joint disorder was diagnosed. With regard to vascular malformations, like other diseases such as inflammatory arthropathy, ultrasonography of the joint may become a new diagnostic approach for evaluating orthopedic manifestations. [ABSTRACT FROM AUTHOR]

Abstracts related to hemophilia are presented including "Acquired Von Willebrand Syndrome: Mechanisms and Response To Treatment" by Pu-Lin Luo, Steve Austin and Mike Laffan, "Treatment of Acute Hemarthrosis At The Hemophilia Patients" by Aziza Makhmudova and Mardon Mukhammadiev and "Validation of a Scale of Adherence to Treatment in Patients With Hemophilia" by Ruben Cuesta-Barriuso, Jose Antonio Lopez-Pina and Manuel Moreno-Moreno.

Objective It is unclear if vascular remodeling in hemophilic joints perpetuates bleeding because it is difficult to gauge leakiness in the setting of low clotting factor levels. Two patients provided the unique opportunity to demonstrate that vascular changes directly contribute to joint bleeding. Approach and Results Two patients had severe hemophilic arthropathies; joint vascularity and bleeding were studied during periods of normalized plasma clotting factor activities with MSKUS and PD. One patient was 'cured' of hemophilia with liver transplantation. Abnormal elbow vascularization persisted despite normalization of coagulation status and was associated with severe bleeding years after transplant. Dynamic vascular changes were detected prior to and during bleeding; angiography revealed enlarged, thickened vessels consistent with remodeling, and required arterial embolization. The second patient had continued knee bleeding and fluctuating vascular changes for months following knee replacement, unresponsive to intense daily factor treatment. Subsequently, new bleeds developed in other joints associated with similar vascular changes despite continued factor replacement. Conclusions Vascular remodeling contributes to perpetuated hemophilic joint bleeding and therefore contributes to progressive arthropathy. Intra-articular or systemic administration of anti-angiogenic drugs, such as vascular endothelial growth factor antagonists, might be of benefit in such patients, but requires study. [ABSTRACT FROM AUTHOR]

This report describes a case of severe supracondylar lysis of the third metatarsal bone of a mature Cob gelding. The gelding presented with moderate to severe lameness and soft tissue swelling in the distal metatarsal region. A mass was present plantar to the third metatarsal bone and dorsal to the suspensory ligament branches. The mass was removed surgically, and was found to be a large blood coagulum within an enlargement of the plantar pouch of the metatarsophalangeal joint. The mass was pedunculated and attached to a region of abnormal synovium. This synovium was identified histologically as being an area of villonodular synovitis. The lesion had similarities with human pigmented villonodular synovitis. Removal of the abnormal tissue resulted in resolution of the lameness and of the lysis of the third metatarsal bone. Haemarthrosis should be considered in the list of differential diagnoses for focally mineralised soft tissue masses found within an articulation, and may be associated with pigmented villonodular synovitis. [ABSTRACT FROM AUTHOR]

Introduction The overlap in symptoms between joint bleeds and flare-ups of haemophilia arthropathy ( HA) creates difficulties in differentiating between the two conditions. Diagnosis of haemarthrosis is currently empirically made based upon clinical presentations. However, no standard diagnostic criteria are available. To offer appropriate treatment, rapid and accurate diagnosis is essential. Additionally, adequate differentiation can decrease health costs significantly. Aim The aim of this study was to identify signs and symptoms to differentiate between an intra-articular joint bleed and an acute flare-up of HA in patients with haemophilia and make an initial proposal of items to include in a diagnostic criteria set. Methods Six focus group interviews with a total of 13 patients and 15 professionals were carried out. The focus groups were structured following the Nominal Group Technique ( NGT). Results The most important signs and symptoms used to differentiate between joint bleeds and HA were (i) course of the symptoms, (ii) cause of the complaints, (iii) joint history, (iv) type of pain and (v) degree of impairments in range of motion. Conclusion This qualitative study provides insight into signs and symptoms that are currently used to differentiate between joint bleeds and flare-ups of HA. Results of this study can be used to develop a valid and standardized clinical diagnostic criteria set to differentiate between these two conditions. Further research is necessary to validate the signs and symptoms found in this study. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include the treatment of patients with low annualised bleeding rates (ABRs), estimation of regular prophylaxis in patients with severe haemophilia A and therapy for recurrent hemarthrosis.

Introduction Knee flexion contracture ( KFC) remains a common complication of haemoarthrosis in children and young adults with haemophilia. If the KFC is not treated properly it produces disability, postural and gait abnormalities. Objective Evaluate the effectiveness of conservative treatment of KFC with Botulinum toxin type A ( BTX-A) in PWH. Methods Seventeen patients were treated, with 21 affected knees. Mean age was 26 years. The mean follow up was 12 months. We evaluated flexion and KFC pretreatment BTX-A and up to 12 months posttreatment. BTX-A application was in hamstring and calf muscles. To evaluate the function, a questionnaire about different activities was made, and it was checked 3, 6 and 12 months after BTX-A. According to the degree of KFC, knees were divided into 3 groups: Group 1: −10° to −30° ( n = 10), Group 2: −31° to −45° ( n = 6) Group 3: −46° or more ( n = 5). Results The average KFC improved from −38° to −24°. The improvement was 14° ( P < 0.001). The average KFC improvement was 9° in group 1, 17° in group 2, and 23° in group 3. There was a high correlation between the improvement in KFC and the total score of the questionnaire R = 0.77. Conclusions Treatment of KFC with BTX-A improves knee-related functional activities, with the advantage of being a low-cost procedure and easy to apply. [ABSTRACT FROM AUTHOR]

Introduction Patients with haemophilia tend to bleed in large joints even during prophylactic replacement therapy. Detection of early blood-induced joint changes may improve monitoring of treatment. The aim of this study was to explore the value of routine ultrasound in detecting early joint abnormalities in children with haemophilia on prophylaxis. Methods Sixty-four joints in 32 children with haemophilia were examined by one operator using the Haemophilia Early Arthropathy Detection with UltraSound protocol during annual multidisciplinary follow-up. Based on reported bleeding, the joint with the highest risk of blood-induced joint damage and the contralateral joint were examined. At the same day, clinical function was assessed according to the Haemophilia Joint Health Score ( HJHS). Results Median age was 11.5 years (range = 5.5-16.4). Out of the 64 examined joints, one ankle was excluded because of previous surgery. Median lifetime joint bleeds/joint was three (interquartile ranges = 1-5). Clinical function of most joints was perfect: only 7/49 joints with reported bleeds scored positive due to swelling, muscle atrophy and/or range of motion loss ( HJHS range = 1-2 points). Ultrasound showed abnormalities in 5/49 joints with reported bleeding, and 4/5 showed positive HJHS scores. Ultrasound abnormalities were present in 1/56 joints (1.8%, CI: 0.1-9.6%) without loss of clinical function. Conclusion Ultrasound abnormalities were found during routine evaluation of joints in children with haemophilia on prophylaxis. Most joints with ultrasound abnormalities showed low HJHS scores too. Ultrasound could be used to evaluate whether minimal losses of clinical function might be caused by anatomical changes. [ABSTRACT FROM AUTHOR]

Introduction Recurrent haemarthrosis in haemophilic patients result with arthropathy of the radiocapitellar joint and blockage of the forearm rotation. Aim The aim of this study is to evaluate the mid-term results of radial head excision with partial synovectomy in severe haemophilic patients retrospectively. Methods Persistent pain and decreased forearm rotation were the main indications for radial head excision. Between 2002 and 2013, radial head excisions were performed for 14 elbows of 14 patients. Eleven patients were haemophilia A, whereas two patients were haemophilia B patients and the remaining one had von Willebrand (Type 3) disease. The mean age of the patients was 29 at the time of the surgery. The mean follow-up was 51 (12-155) months. VAS (visual analogue score) for pain, forearm rotation, qDASH and MEPS (Mayo Elbow Performance Score) were used as the primary outcome parameters. Results The mean VAS decreased significantly from 6.5 preoperatively to 2.2 at the final follow-up ( P = 0.0003). The mean forearm rotation increased from 40° to 115° respectively ( P = 0.0007). In two patients, efficacious rotation increase was not achieved due to distal radioulnar joint problems. The mean qDASH score and MEPS were 18.1 and 87.5 at the latest follow-up, respectively, where four patients had excellent and 10 patients had good results. Conclusions Radial head excision is a safe and effective procedure for haemophiliac patients with radiocapitellar arthropathy and decreased forearm rotation. Distal radioulnar joint should be evaluated preoperatively which may impair the results. [ABSTRACT FROM AUTHOR]

Marstacimab, an investigational human monoclonal antibody targeting tissue factor pathway inhibitor, demonstrated safety and efficacy in preventing bleeding episodes in patients with haemophilia. This multicentre, open-label study investigated safety, tolerability, and efficacy of long-term weekly prophylactic marstacimab treatment in participants with severe haemophilia A and B, with or without inhibitors. Adult participants were enrolled from a previous phase Ib/II study or de novo and assigned to one of two subcutaneous (SC) marstacimab doses: once-weekly 300 mg or a 300-mg loading dose followed by once-weekly 150-mg doses, for up to 365 days. Study end-points included safety assessments and annualised bleeding rates (ABRs). Of 20 enrolled participants, 18 completed the study. Overall, 70% of participants had treatment-emergent adverse events, including injection site reactions, injection site haematoma, and haemarthrosis. No treatment-related serious adverse events or thrombotic events occurred. Across all dose cohorts, mean and median on-study ABRs ranged from 0 to 3.6 and 0 to 2.5 bleeding episodes/participant/year respectively, demonstrating comparable efficacy to that observed in the short-term parent study. No treatment-induced anti-drug antibodies were detected. Once-weekly SC marstacimab prophylaxis was well tolerated, with an acceptable safety profile, and maintained long-term efficacy up to 365 days. (Clinicaltrials.gov identifier, NCT03363321)., (© 2022 Pfizer, Inc and The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence. Aims We report the data available in the literature on FVII prophylaxis and our personal experience regarding three patients affected by severe FVII deficiency. Methods Specific papers on long-term prophylaxis in severe FVII deficiency were identified using the database, PUBMED. Results The most frequent indications for long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding (9%). Patients were treated with various dosages and frequency. Prophylactic treatment with 10-30U/kg (pd FVII) or 20-30mcg/kg ( rFVIIa) twice or three times/weeks was described to be effective. Conclusions In the literature and in our experience, prophylaxis can be considered in patients with severe FVII deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pd FVII) or 20-30 microg/kg ( rFVIIa) twice or three times/week is usually administrated, but dose and frequency can be tailored based on the clinical follow-up of the patients. Since hemarthrosis is a frequent manifestation, a suggestion to improve the outcomes of patients with severe FVII deficiency is to monitor joint condition in order to identify early arthropathy that could be another indication to start secondary prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction In haemophiliacs, recurrent hemarthrosis and chronic synovitis lead to chronic arthropathy. Synovectomy is indicated when medical treatment fails. Few studies report the results of open synovectomy of the ankle in haemophiliacs with a small number of procedures and also a limited follow-up. Aim The aim of this paper is to report the long-term results of open surgical synovectomy of the tibio-talar joint. Methods Thirty-two open synovectomies were performed in 21 young haemophiliacs in the same haemophilia center using an antero-lateral and postero-medial approaches. The median follow-up was 15.4 years. Clinical (Petrini scores) and radiological evaluations (Pettersson scores) were made preoperatively and at each multidisciplinary follow-up visit. Wilcoxon and Spearman's tests were used for the statistical analysis. Results Preoperative median Petrini score was 6 (range 3-12), and improved at 2 and 5 years follow-up ( P = 0.0003 and P = 0.0001 respectively). At 10 and 15 years follow-ups, median score remained below preoperative score (median 3.5, range 0-11). Ten ankles had a follow-up of more than 20 years. Preoperative median Petterson score presented a slight but continuous worsening in the first 2 and 5 years of follow-ups ( P = 0.02, P = 0.003), but not correlation between clinical and radiological results was observed. Conclusion Our long-term results support that clinical scores are improved even if radiological scores progress. Open synovectomy retards the progression of the arthropathy, but not stops it. Bleeding and pain are controlled and even if recurrence of bleedings is frequent, it is less severe, less painful and requiring less factors replacement. [ABSTRACT FROM AUTHOR]

Introduction Elderly patients with haemophilia ( PWH) suffer from both haemarthrosis and haemophilic arthropathy ( HA). Diagnosis of haemarthrosis in PWH is currently based on clinical presentation. No diagnostic protocols or validated criteria are available to identify haemarthrosis or to differentiate haemarthrosis from HA. Aim The aim of this study is to identify symptoms and signs that can be used to differentiate haemarthrosis from HA. Methods A narrative literature review was performed on symptoms associated with haemarthrosis and symptoms associated with HA. Additionally, literature on the diagnosis of haemarthrosis in patients without haemophilia, imaging techniques and biomarkers was searched. Results This review shows that there is no consensus about the symptoms associated with haemarthrosis and that there is limited literature about the symptoms associated with HA. Additionally, symptoms associated with haemarthrosis partly overlap with symptoms of HA, particularly those symptoms associated with flare-ups of HA. Due to the overlap in symptoms differentiating between these conditions is complex. Furthermore, differentiating based on imaging techniques or biomarkers causes practical difficulties. Conclusion Despite the overlap in symptoms, differentiating between joint bleeds and flare-ups of HA based on clinical presentation still seems the most convenient and practical solution. Further research is necessary to identify specific symptoms that can be used to differentiate between the two conditions. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on haemarthrosis home treatment in patients with haemophilia A through home delivered ultrasound monitoring.

Prophylaxis prevents joint and other bleeding episodes in patients with haemophilia A. Development of new factor concentrates with longer circulating half-lives may encourage patients to start, continue or resume prophylaxis. The aim of this study was to compare the pharmacodynamic effect of a PEGylated full-length recombinant factor VIII ( rFVIII) concentrate with that of an unmodified rFVIII concentrate with respect to the duration of prophylactic efficacy in a murine model of haemophilic joint bleeding. Mice were pretreated with BAX 855 or unmodified rFVIII at specified times before right knee puncture to induce haemarthrosis; left knee joints served as controls. Joint bleeding was evaluated using a combination of visual and histological assessments. Administration of a single dose of unmodified rFVIII before joint puncture prevented haemarthrosis in mice up to 24 h, whereas pretreatment with BAX 855 protected the joint from bleeding up to 48 h. This pharmacodynamic study showed prolonged efficacy of BAX 855 compared to ADVATE in a haemophilia A mouse joint bleeding model. This finding supports the possibility of using BAX 855 to increase FVIII trough levels and/or extend the dosing interval in patients with haemophilia A on prophylaxis, which may potentially improve prophylactic efficacy and long-term adherence. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the development of anti-Factor VIII immune response inhibitors in the context of acute local bleeding in severe haemophilia A mice. The study involves the development of haemarthrosis-induced arthropathy validated by measuring the outer diameter of the knees, days after knee injury. The anti-FVIII IgG in serum was detected by ELISA. The study revealed that haemarthrosis and arthropathy do not favour the development of Factor VIII.

The article presents a case study of a 19-year-old man referred a haemostasis laboratory with severe bleeding phenotype. The patient has a history of prolonged umbilical cord haemorrhage and has suffered a subdural haematoma, recurrent subcutaneous bleeding, intramuscular haematomas and haemarthroses. Assessments revealed the use of first recombinant factor XIII in a major bleeding episode with congenital factor XIII deficiency.

Prophylaxis has become the standard mantra of care for those individuals with severe haemophilia A and B. Primary prophylaxis is advocated to prevent the occurrence of symptomatic acute spontaneous haemarthroses and to preserve joint structure and function. Typically, twice or thrice weekly infusions of factor VIII or IX concentrates are integral to this treatment approach. Secondary prophylaxis is initiated after the relentless cycle of progressive joint damage has been triggered by prior haemarthroses and is intended to preserve existing joint health by preventing additional spontaneous bleeding events. Event-driven prophylaxis involves the administration of clotting factor concentrates to prevent acute traumatic bleeds, which are anticipated to occur in association with surgical or physical trauma. This regimen enhances the effectiveness of primary or secondary prophylaxis protocols or on-demand approaches to replacement therapy. Besides the marked reduction in the so-called annual bleed rate, prophylaxis regimens frequently increase personal self-confidence to embark on a more active and physical lifestyle; however, in reality, prophylaxis must be individualized in accordance with bleeding phenotypes, with the unique pharmacokinetic profile of administered replacement clotting factor concentrates, with the specific clinical scenario, and with the degree of intensity anticipated for any physical activity. The introduction of extended half-life replacement products will also influence how these prophylaxis regimens will be accomplished. The following scenarios will discuss how prophylaxis regimens can be implemented to protect the individual from developing spontaneous and activity-induced acute bleeding complications and to maintain an improved quality of life. [ABSTRACT FROM AUTHOR]

Chronic pain, most often due to haemophilic arthropathy, is a pervasive problem in persons with haemophilia ( PWH) that adversely impacts function and quality of life. PWH with inhibitors and older PWH may be especially vulnerable to progressive arthropathy and resulting chronic pain. The development of chronic pain from acute pain involves a complex interplay of biological and psychosocial factors that may all contribute to the perpetuation of chronic pain and the outcome of therapy. In the absence of evidence-based guidelines, an individualized, multimodal approach to chronic pain management is proposed, as it is in individuals without haemophilia who have chronic pain. Pharmacological treatment is central to the management of chronic pain and must be modified based on pain intensity, ongoing response to therapy and the risk for adverse events. Non-pharmacological interventions, including physiotherapy, complementary treatments and surgical (e.g. orthopaedic) or other invasive procedures, may be integral to chronic pain management in this population. Ongoing psychosocial assessment is critical to identify those factors that may be contributing to the perpetuation of chronic pain or acting as barriers to effective management. Additional study is needed to identify optimal pharmacological treatments for chronic pain in PWH based on the unique pathophysiology of haemophilic arthropathy and on risk profile. Systematic determination of the particular psychosocial factors impacting the experience and management of chronic pain in PWH would likewise add value to the treatment of this pervasive problem. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 46-year-old patient with severe haemophilia A, without circulating inhibitor, HIV-positive and hepatitis C-positive. The patient suffered severe arthropathy of both knees with intense pain in the left knee for several years. It highlights the severe postoperative haemarthrosis following a total knee replacement in the haemophiliac patient. It also emphasizes the importance of early diagnosis and treatment of the complication through arterial embolization.

The phenotypic variability in haemophilia is well documented; however, the biological basis beyond factor VIII and IX activities to explain the differing clinical pictures of the disease remains unclear. It has therefore been of interest to explore other modulators of the disease's variability. Furthermore, a scoring system that reflects the multiple facets of haemophilia symptoms would be useful to compare patients via a comprehensive assessment tool. To this end, Schulman et al., created a measure known as the Haemophilia Severity Score ( HSS) as one way to compare phenotypic severity. The aim of this study was to document the differing symptomatology of haemophilia patients using the HSS. Clinical data for 178 haemophilia patients without inhibitors were reviewed and annual incidence of haemarthrosis, orthopaedic joint scores and annual factor usage calculated. Each parameter was then entered into the formula to create the HSS for haemophilia A and B patients with mild, moderate and severe factor deficiencies. Variability in the HSS for patients with the same baseline level of factor was observed for all three deficiency levels and both haemophilia types. In addition, we found that moderate and severe haemophilic B patients tended to have more morbidity based on the above calculations than the haemophilic A counterparts. The HSS is a comprehensive tool that allows for easy numerical comparison of haemophilic patients and elucidates the variable clinical presentation of the disease. The HSS could be used to stratify patients via other possible modulators of haemophilia and discover other aetiologies of the disease. [ABSTRACT FROM AUTHOR]

Our purposes were to determine: (i) whether there is direct evidence that currently available MRI techniques are accurate for early diagnosis of pathological findings in haemophilic arthropathy; (ii) whether there is an MRI scoring system that best correlates with clinical/radiological constructs for evaluation of haemophilic arthropathy; (iii) whether there is an MRI scoring system that best correlates with clinical/radiological constructs for evaluation of haemophilic arthropathy. Articles were screened using MEDLINE ( n = 566), EMBASE ( n = 201), and the Cochrane Library ( n = 1). Two independent reviewers assessed articles for inclusion under the overarching purposes of the review by using the Standards for Reporting of Diagnostic Accuracy ( STARD) tool, and the quality of the studies were graded using the Quality Assessment of Diagnostic Accuracy Studies 2 ( QUADAS-2) tool. The electronic literature search retrieved 777 references (after duplicates were removed). A total of 32 studies were chosen for inclusion from the results of the search and review of bibliographical references. Using the STARD tool, seven studies were of excellent quality of reporting, and using the QUADAS-2 tool, 10 studies were judged to be of adequate quality. There is 'fair' evidence to recommend MRI as an accurate test for detecting evidence of haemophilic arthropathy and the use of second or third generation MRI scales for assessing haemophilic arthropathy. However, there is no evidence that screening of early intra-articular soft tissue bleed with MRI improves the functional status of joints over time. [ABSTRACT FROM AUTHOR]

The increasing attention to healthcare costs and treatment efficiency has led to an increasing demand for quantitative data concerning patient and treatment characteristics in haemophilia. However, most of these data are difficult to obtain. The aim of this study was to use expert judgement elicitation ( EJE) to estimate currently unavailable key parameters for treatment models in severe haemophilia A. Using a formal expert elicitation procedure, 19 international experts provided information on (i) natural bleeding frequency according to age and onset of bleeding, (ii) treatment of bleeds, (iii) time needed to control bleeding after starting secondary prophylaxis, (iv) dose requirements for secondary prophylaxis according to onset of bleeding, and (v) life-expectancy. For each parameter experts provided their quantitative estimates (median, P10, P90), which were combined using a graphical method. In addition, information was obtained concerning key decision parameters of haemophilia treatment. There was most agreement between experts regarding bleeding frequencies for patients treated on demand with an average onset of joint bleeding (1.7 years): median 12 joint bleeds per year (95% confidence interval 0.9-36) for patients ≤18, and 11 (0.8-61) for adult patients. Less agreement was observed concerning estimated effective dose for secondary prophylaxis in adults: median 2000 IU every other day The majority (63%) of experts expected that a single minor joint bleed could cause irreversible damage, and would accept up to three minor joint bleeds or one trauma related joint bleed annually on prophylaxis. Expert judgement elicitation allowed structured capturing of quantitative expert estimates. It generated novel data to be used in computer modelling, clinical care, and trial design. [ABSTRACT FROM AUTHOR]

Little objective information exists about musculoskeletal bleeding patterns in haemophilic arthropathy. Bleeding is assumed to be the cause of painful joints or muscles. Clotting factor treatment is provided empirically, but often does not alleviate pain. We hypothesized that perception of pain aetiology is unreliable, and introduced point-of-care high-resolution musculoskeletal ultrasound ( MSKUS) to differentiate intra-articular bleeds vs. joint inflammation, and intra-muscle bleeds vs. other regional pain syndromes. To assess painful musculoskeletal episodes in adult haemophiliacs, we used rapid MSKUS, employing grey scale and power Doppler examination. Forty episodes in 30 adult haemophiliacs were evaluated. Thirty three of the 40 episodes were patient-reported as 'bleeding', five as 'arthritis-type' pain and two as 'undecided'. Of the 33 bleeding reports, only 12 were confirmed by MSKUS; the other episodes revealed other pathology. In contrast, three of five perceived arthritis flares were reclassified as bleeds. Similarly, physician assessment was incorrect in 18 of 40 instances. Swelling and warmth were present in approximately half of confirmed bleeding and non-bleeding episodes, and therefore not useful clinically. Few of the painful episodes were symptom controlled at the time of MSKUS. Management changed based on objective imaging findings in >70% of episodes, which resulted in symptom improvement >60% of the time. Significant discrepancies exist between MSKUS findings and patient/physician-perceived pain classification as bleeding or other musculoskeletal symptoms. Current practice of prescribing clotting factor or conservative measures based on pain perception seems inadequate and suggests that point-of-care imaging should be included into modern haemophilia care. [ABSTRACT FROM AUTHOR]