Study of platelet kinetics in immune thrombocytopenia to predict splenectomy response.

Despite the efficacy of splenectomy for chronic immune thrombocytopenia (ITP), its considerable failure rate and its possible related complications prove the need for further research into potential predictors of response. The platelet sequestration site determined by 111 In-labelled autologous platelet scintigraphy has been proposed to predict splenectomy outcome, but without standardisation in clinical practice. Here, we conducted a single-centre study by analysing a cohort of splenectomised patients with ITP in whom 111 In-scintigraphy was performed at La Paz University Hospital in Madrid to evaluate the predictive value of the platelet kinetic studies. We also studied other factors that could impact the splenectomy outcome, such as patient and platelet characteristics. A total of 51 patients were splenectomised, and 82.3% responded. The splenic sequestration pattern predicted a higher rate of complete response up to 12 months after splenectomy (p = 0.005), with 90% sensitivity and 77% specificity. Neither age, comorbidities, therapy lines nor previous response to them showed any association with response. Results from the platelet characteristics analysis revealed a significant loss of sialic acid in platelets from the non-responding patients compared with those who maintained a response (p = 0.0017). Our findings highlight the value of splenic sequestration as an independent predictor of splenectomy response.

Predicting joint involvement through tailored prophylaxis in severe haemophilia A, is it possible?

INTRODUCTION: Tailored prophylaxis is the current treatment regimen for patients with severe haemophilia A. Recently, published guidelines describe two possible approaches, based on clinical characteristics or estimation of pharmacokinetic parameters. However, both have strengths and weaknesses, and their characteristics need to be integrated to optimize treatment appropriately. In this paper, we present a model that considers together the characteristics of prophylaxis and the relevance of each. METHODS: The age at initiation of prophylaxis, number of bleeding events, treatment regimen, therapeutic adherence, FVIII trough levels, and joint status were analyzed in 59 patients followed at La Paz University Hospital between January 2000 and December 2019. RESULTS: The mean duration of primary prophylaxis of 113.37 ± 57.79 months. Eighty-three percent (n = 49) had no joint status involvement at the end of follow-up (HJHS and HEAD-US = 0). The median ABR was 0.7 (IQR 0.2 -1.0) and 54.2% presented trough levels of FVIII during follow-up >1 IU/dL. 72,9% engaged in some type of physical activity and overall adherence was over 85% in all patients evaluated. The regression analysis performed, considering all these factors, showed that the initiation of prophylaxis before 21 months of age was the most relevant protective factor against the appearance of joint involvement (OR 88.33 p.031 CI 95% 1.49-5224.40) CONCLUSION: Early initiation of prophylaxis was the most relevant factor in the protection of joint status. More comprehensive analysis models adapted to the characteristics of each population, are needed to adequately individualize treatment.

Arthroscopic ankle surgery in people with haemophilia.

INTRODUCTION: People with haemophilia (PWH) not administered primary haematological prophylaxis since childhood, that is, those treated haematologically on demand or not treated at all, often experience the degeneration of the ankles, leading to pain and functional impairment. AIM: To analyse the outcomes and complications of arthroscopic ankle surgery performed on PWH. METHODS: For this narrative review of the literature, a search was conducted in PubMed on 2, December 2023, using the keywords "haemophilia", "ankle" and "arthroscopy". Of the 29 articles identified, 15 specifically related to ankle arthroscopy in PWH were selected (inclusion criterion). The remaining articles did not meet this requirement (exclusion criterion) and were therefore eliminated. RESULTS: Arthroscopic procedures (arthroscopic synovectomy, debridement and arthrodesis of the ankle) are increasingly used in the surgical treatment of haemophilic ankle arthropathy. Although arthroscopic ankle surgery offers good outcomes in patients with haemophilia, the procedure is not free of complications, which range from 7.9% for arthroscopic ankle debridement to 13.1% in arthroscopic ankle synovectomy and 17.8% in arthroscopic ankle arthrodesis, respectively. The non-union rate of arthroscopic ankle arthrodesis is 7.1% (2/28). CONCLUSION: Although arthroscopic interventions in the haemophilic ankle (synovectomy, debridement, arthrodesis) offer good functional outcomes, they are associated with a non-negligible rate of complications. Arthroscopic ankle surgery in PWH is major surgery and should be treated as such.

A post hoc comparative real-world analysis of HEAD-US score for joint health assessment of patients with severe haemophilia A and B in Spain.

AIM: Joint damage due to haemarthrosis can be effectively monitored with point-of care ultrasound using the Haemophilia Early Arthropathy Detection with US (HEAD-US) scoring system. A post hoc comparative analysis of the joint status of patients with severe haemophilia A (HA) or B (HB) was performed. METHODS: The databases of two observational, cross-sectional studies that recruited patients with HA or HB from 12 Spanish centres were analysed to compare the status of the elbows, knees and ankles in patients with severe disease according to treatment modality. The HEAD-US score was calculated in both studies by the same trained operators. RESULTS: Overall, 95 HA and 41 HB severe patients were included, with a mean age of 35.2 ± 11.8 and 32.7 ± 14.2 years, respectively. The percentage of patients who received prophylaxis, over on-demand (OD) treatment, was much higher in HA (91.6%) than in HB (65.8%) patients. With a similar number of target joints, the HEAD-US score was zero in 6.3% HA and 22.0% HB patients (p < .01), respectively. The HA population showed significantly worse HEAD-US scores. Whilst osteochondral damage occurred more frequently in patients OD or tertiary prophylaxis, our data suggest that articular damage is less prominent in primary/secondary prophylaxis, regardless of the type of haemophilia. These latter treatment modalities were also associated with a lower prevalence of synovial hypertrophy, particularly in HB patients. CONCLUSION: This post hoc analysis indicates that joint status seems to be significantly influenced by haemophilia type (HA or HB) and treatment modality in these severe Spanish populations with severe disease. Continuing HEAD-US monitoring for the early detection and management of intra-articular abnormalities, as well as more efficiently tailored therapies should be warranted.

Safety and efficacy of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A: Results of an interventional, post-marketing study.

INTRODUCTION: Damoctocog alfa pegol (BAY 94-9027, Jivi® ) is an approved extended half-life factor VIII (FVIII) for treatment of previously treated patients with haemophilia A aged ≥12 years. We report the final results of an interventional, post-marketing study of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A. METHODS: In this open-label, interventional, post-marketing, phase 4 trial (NCT04085458), previously FVIII-treated patients with severe haemophilia A aged ≥18 years received damoctocog alfa pegol for ≥100 exposure days (EDs). Patients initially received 45 IU/kg every 5 days (recommended) or 40 IU/kg twice-weekly. At Visit 3, patients' doses could be increased, or treatment frequency adapted. The primary endpoint was FVIII inhibitor development (titre ≥.6 Bethesda units). Secondary endpoints included anti-polyethylene glycol (PEG) antibody development, treatment-emergent adverse events (AEs) and annualized bleeding rate (ABR). RESULTS: Overall, 36 patients were enrolled; 32 patients received treatment, of whom, 27 completed the study. No patients developed FVIII inhibitors; three tested transiently positive for low-titre anti-PEG antibodies without clinical relevance. Three patients reported study-drug-related AEs of mild or moderate intensity. Two patients discontinued the study due to AEs. No deaths occurred. Most patients (70%) were treated with E5D/E7D regimens. The median (Q1;Q3) total ABR (N = 30) was 3.0 (.0;9.0) pre-study and 1.8 (.7;5.9) during the study. CONCLUSION: Damoctocog alfa pegol individualized prophylaxis regimens were well-tolerated with no immunogenicity concerns. ABRs improved following the switch from pre-study prophylaxis to damoctocog alfa pegol prophylaxis. These results support the favourable safety and efficacy profile of damoctocog alfa pegol prophylaxis.

Humanistic burden of haemophilia A without inhibitors: A cross-sectional analysis of the HemoLIFE study.

AIM: To evaluate the impact of haemophilia A without inhibitors on humanistic outcomes in patients and caregivers. Herein, we report a cross-sectional analysis of the baseline data of persons with haemophilia (PWH) participating in the prospective study HEMOLIFE. METHODS: These data are part of a prospective, observational, and multicentre study currently being conducted in 20 hospitals in Spain by haematologists. We included subjects 12 years or older diagnosed with haemophilia. The evaluations included the Maladjustment Scale, Haemophilia-Specific Quality of Life Questionnaire for Adults (HaemoQol)/HaemoQol Short Form (Children), haemophilia-specific version of the Work Productivity and Impairment Questionnaire plus the Classroom Impairment Questionnaire (WPAI+CIQ:HS), Haemophilia Activity List (HAL)/Paediatric Haemophilia Activities List (pedHAL), visual analogue scale (VAS) for evaluating pain, Coping Pain Questionnaire-Reduced (CAD-R), and Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 81 PWH were recruited at 18 centres; 66 PWH were ≥18 years (i.e., adults), and PWH 15 were <18 years (i.e., paediatric patients). Out of the 79 evaluable subjects, 16 (20%) showed an impact of haemophilia on daily life, and the areas most affected were "leisure time" (58% showed maladjustment) and "work/studies" (47% showed maladjustment). Patients reported a higher impact of haemophilia on quality of life (mean [SD] of the transformed score) in the dimensions of "sport" (49.4 [28.6]), "physical health" (40.5 [25.8]) and "future" (37.7 [28.9]). In adults, according to HAL scores, greater impairment of function was observed in "lying/sitting/kneeling/standing," "function of legs" and "leisure activities and sports," with mean normalized scores of 64.7, 65.1 and 69.0, respectively. Productivity was mostly impacted by presenteeism. The pain was infrequent and moderate. According to the HADS scores, nine (11.5%) patients had clinical anxiety and depression. CONCLUSION: PWH without inhibitors exhibited impairments in adjustment, quality of life and functionality, especially related to leisure and sports activities, and exhibit relevant levels of anxiety and depression.

Interim analyses of the multinational real-world prospective cohort HEM-POWR study evaluating the effectiveness and safety of damoctocog alfa pegol in patients with hemophilia A.

OBJECTIVES: To assess effectiveness and safety of damoctocog alfa pegol in interim analyses of the ongoing real-world hemophilia A HEM-POWR study. METHODS: HEM-POWR (NCT03932201) is a multinational Phase 4 prospective observational study. The primary objective was annualized bleeding rate (ABR) in previously treated patients (PTPs) with hemophilia A. Secondary objectives included adverse events and number of affected joints. RESULTS: At data cut-off (August 17, 2022), the safety analysis set included 268 patients and the full analysis set (FAS) included 161 patients. The most common dosing regimen during observation period was prophylaxis (FAS = 158/161, 98.1%) every 3-4 days (twice weekly; FAS = 78/158, 49.4%) and a median (min, max) infusion dose of 37.5 (10, 72) IU/kg. PTPs receiving prophylactic damoctocog alfa pegol have fewer infusions compared with prior treatment. Median total ABR (Q1, Q3) was 0.0 (0.0, 1.8) and mean total ABR (SD) was 2.4 (8.2). The proportion of patients with no affected joints increased between initial visit and follow-up. No FVIII inhibitors, treatment-related adverse events, or deaths were reported. CONCLUSIONS: Damoctocog alfa pegol shows effectiveness and acceptable safety, as well as consistent utilization, in real-world PTPs with hemophilia A, including in patients with non-severe hemophilia and those with a history of inhibitors. Please see video for a summary of this study.

Assessing coagulopathy and endothelial dysfunction in pediatric venous malformation: A thromboelastometry and syndecan-1 study.

OBJECTIVE: The occurrence of unpredictable pain crises are the principal determinant of the quality of life for patients with venous malformations (VM). A definite coagulation phenomenon, characterized by an increase in D-dimer levels and the presence of phleboliths within the malformation, has been previously reported. By applying Virchow's triad and evaluating intralesional samples, our objective is to delineate the coagulation profile and the extent of endothelial dysfunction within the malformation. METHODS: With the authorization of the Ethics Committee, a research project was undertaken on intralesional and extralesional blood samples from 30 pediatric patients afflicted with spongiform VM. Thromboelastometry analyses were performed using ROTEM Sigma, and the concentration of syndecan-1 was determined by ELISA. RESULTS: In the ROTEM analyses, the A5, A10, and maximum clot firmness (MCF) values were below the established reference ranges in the intralesional samples in both the EXTEM and INTEM assays, indicating that intralesional clots had significant instability. Furthermore, during the investigation of the delayed fibrinolysis phase using recombinant tissue plasminogen activator (rtPA) in EXTEM analysis, widespread hyperfibrinolysis was observed intralesional. Additionally, analysis of syndecan-1 showed significant differences between extralesional and intralesional levels (p < .026) and controls (p < .03), suggesting differences in the state of endothelium. CONCLUSIONS: For the first time, we developed a comprehensive understanding of the coagulopathic profile of VM and the role of endothelial dysfunction in its pathogenesis. These findings will enable the implementation of targeted therapies based on the individual coagulation profiles.

Switching and increasing prophylaxis regimen with a genetically recombinant fusion of coagulation factor IX and albumin in haemophilia B: a case report.

PURPOSE OF REVIEW: We present a case of a boy diagnosed in 2007 with severe haemophilia B [factor IX (FIX) concentration < 1%] at age of 9 months. He was initially treated with recombinant FIX concentrates, but changes in regimens were frequent due to spontaneous hemarthros. In 2013, he entered a phase III trial (NCT01662531) and received rIX-FP, IDELVION at 50 IU/kg once a week. Although the boy was safely maintained with this regimen (2015-2017), the number of hemarthros increased after he started to play football. Thus, rIX-FP regimen was modified (40 IU/kg twice/week) to optimize therapy. This modification was efficient on maintaining patient's thought levels (33%), helped during his fully incorporation at school and social life, and significantly improved synovial hypertrophy. In the last year, the boy has not suffered any bleeding episode and his joint situation improved significantly, which allowed reducing doses to weekly recommended doses. RECENT FINDINGS: FIX replacement therapies with intravenous plasma-derived FIX (pdFIX) or standard half-life recombinant FIX (rFIX) concentrates are hampered by the relatively short terminal elimination half-life (t1/2) of these substances (around 17-34 h), resulting in the need for frequent infusions (e.g. once every 3 or 4 days) to maintain protective FIX levels. In the past years, the first genetically recombinant fusion of rFIX with another protein - a recombinant human albumin - was developed (albutrepenonacog-alfa or rIX-FP; IDELVION) as a strategy to extend the t1/2 of rFIX-FP (around 95 h). SUMMARY: We provide information about the difficult management of a patient with a major bleeding haemorrhagic phenotype, which caused serious limitations in the patient's daily life, impacting his quality of life at his young age, and how the switch to IDELVION allowed the situation to improve considerably.

Clinical assessment and point of care ultrasonography: How to diagnose haemophilic synovitis.

BACKGROUND: The ability of clinical tools to identify early joint changes is limited. Synovitis is a fundamental finding in understanding haemophilia activity and the response to its therapies; thus, there is a need for sensitive methods to better diagnose subclinical synovitis early. PURPOSE: Our aim was to compare the frequency with which clinical assessment and ultrasound detected synovial hypertrophy in the most frequently affected joints in patients with haemophilia (elbows, knees and ankles). METHODS: We analysed patients with haemophilia older than 16 years who came to the haemophilia centre for routine follow-up. From the clinical assessment carried out in the consultation, the swelling, pain and history of haemarthrosis were evaluated and compared with the findings of synovial hypertrophy detected by ultrasound. This comparison was also analysed independently for elbows, knees and ankles. RESULTS: A total of 203 joints of 66 patients with haemophilia (mean age 34 years), most of them on secondary, tertiary prophylaxis or on demand treatment, were included. In joints with swelling, pain and history of haemarthrosis, 78% of the joints showed synovial hypertrophy on ultrasound. However, in joints with no swelling, no pain and no history of haemarthrosis, 40% presented subclinical synovial hypertrophy on ultrasound. This percentage was higher in elbows than in knees and ankles. CONCLUSION: In adults with haemophilia, physical examination and point-of-care ultrasound study provide complementary data on their joint disease. However, without ultrasound, the ability to detect subclinical synovitis is considerably reduced, especially in the elbows.

Plasma-derived FVIII/VWF complex shows higher protection against inhibitors than isolated FVIII after infusion in haemophilic patients: A translational study.

INTRODUCTION: Presence of von Willebrand factor (VWF) in FVIII concentrates offers protection against neutralizing inhibitors in haemophilia A (HA). Whether this protection is more evident in plasma-derived (pd) FVIII/VWF or recombinant (r) FVIII concentrates remains controversial. AIM: We investigated the protection exerted by VWF against FVIII inhibitors in an in vivo mouse model of HA exposed to pdFVIII/VWF or to various rFVIII concentrates. METHODS: Haemophilia A mice received the different FVIII concentrates after administration of vehicle or an inhibitory IgG purified from a commercial pool of HA plasma with inhibitors and FVIII:C recoveries were measured. Furthermore, using a novel clinically oriented ex vivo approach, Bethesda inhibitory activities (BU) of a commercial pool of HA plasma with inhibitors were assessed using normal plasma, or plasma from severe HA patients, without inhibitors, after treatment with the same concentrates. RESULTS: in vivo studies showed that pdFVIII/VWF offers markedly higher protection against inhibitors when compared with any of the FVIII products without VWF. More importantly, in the ex vivo studies, plasma from patients treated with pdFVIII/VWF showed higher protection against inhibitors (P values ranging .05-.001) in comparison with that observed in plasma from patients who received FVIII products without VWF, regardless of the type of product evaluated. CONCLUSION: Data indicate that FVIII+VWF complexes assembled in the circulation after rFVIII infusion are not equivalent to the naturally formed complex in pdFVIII/VWF. Therefore, rFVIII infused into HA patients with inhibitors would be less protected by VWF than the FVIII in pdFVIII/VWF concentrates.

Ultrasound evaluation of joint damage and disease activity in adult patients with severe haemophilia A using the HEAD-US system.

INTRODUCTION: The Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) system and scoring scale has proven to be an accurate and time-efficient imaging method for identifying joint damage in patients with haemophilia. AIM: Observational, multicentre, cross-sectional study conducted in 8 centres in Spain that assessed the joint status of adult patients with severe haemophilia A (SHA) using HEAD-US. METHODS: Joint status of the elbow, knee and ankle was evaluated in adults with SHA receiving on-demand (OD) treatment, or primary (PP), secondary (SP), tertiary (TP) or intermittent (IP) prophylaxis. RESULTS: Of the 95 patients enrolled, 87 received prophylaxis (6.3% PP, 38.9% SP, 43.2% TP and 3.2% IP). Mean age was 35.2 years, and 59% of patients had not undergone image testing in the last year. The HEAD-US score was 0 in all joints in 6.3% of patients. The ankle was the most affected joint, regardless of treatment regimen. Patients receiving OD treatment, TP or IP had the overall worst scores, mainly in the ankles and elbows; a similar but milder profile was observed in patients on SP; and patients on PP had the best score in all joints. CONCLUSION: Joint function may be effectively preserved in patients with SHA on PP, but OD treatment or later initiation of prophylaxis does not seem to prevent progression of arthropathy. Disease worsening was observed in patients OD, TP or IP, most often affecting ankles and elbows. Closer ultrasound imaging monitoring may improve management of these patients.

Platelet and immune characteristics of immune thrombocytopaenia patients non-responsive to therapy reveal severe immune dysregulation.

Multifactorial mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) might condition the ability of patients with ITP to respond to treatments. Examining their platelet and immune features, we aimed to detect singular characteristics of patients with ITP who do not respond to any treatment. We studied patients with chronic primary ITP who had been without treatment, or untreated (UT-ITP), for at least six months; included were responders to agonists of thrombopoietin receptors (TPO-RA), patients who showed no response to first- and second-line treatments (NR-ITP), and healthy controls. Platelets from NR-ITP patients exposed a reduced amount of sialic acid residues. Increased loss of platelet surface sialic acid residues was associated with increased platelet apoptosis. NR-ITP patients had an increased fraction of naive lymphocyte (L) B cells and a reduced LTreg (Lymphocyte T-regulator) subset. They also presented an anomalous monocyte and NK (Natural Killer) cells distribution. TPO-RA-treated patients seemed to recover an immune homeostasis similar to healthy controls. In conclusion, our results indicate a severe deregulation of the immune system of NR-ITP. The inverse correlation between loss of sialic acid and LTreg count suggests a potential relationship between glycan composition on the platelet surface and immune response, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP.

Registry of patients with congenital bleeding disorders and COVID-19 in Madrid.

INTRODUCTION: We present the first registry of patients with congenital bleeding disorders and COVID-19. The study has been carried out in the Community of Madrid, which has the highest number of cases in Spain. The objective is to understand the incidence of COVID-19, the course of the disease if it occurs and the psychosocial and occupational impact on this population. METHODS: We included 345 patients (246 of haemophilia, 69 of von Willebrand Disease, two rare bleeding disorders and 28 carriers of haemophilia). A telephone survey was used to collect the data. RESULTS: Forty-two patients presented symptoms suggestive of infection by COVID-19, and in six cases, the disease was confirmed by RT-PCR. The cumulative incidence of our series was 1.73%. It is worth noting the complexity of the management of COVID-19 in two patients on prophylaxis with non-factor replacement therapy. Adherence to the prescribed treatment was maintained by 95.5% of patients. Although 94% were independent for daily living activities, 42.4% had a recognized disability and 58% required assistance, provided by the Madrid Haemophilia Association (Ashemadrid) in 75% of cases. Only 4.4% of consultations were held in person. CONCLUSIONS: Patients with congenital bleeding disorders infected with SARS-CoV-2 presented a mild course of the disease that did not require admission. Their identification and treatment by a specialist team from a Haemophilia Treatment Center are essential to make a correct assessment of the risk of haemorrhage/thrombosis. COVID-19 had a major impact on the psychosocial aspects of these patients which must be remedied with recovery plans.

Prophylaxis therapy with bypassing agents in patients with haemophilia A and inhibitors undergoing surgery: A cost analysis in Spain.

OBJECTIVES: This study estimated the cost of prophylaxis with activated prothrombin complex concentrate (aPCC) and recombinant activated factor VIIa (rFVIIa) in surgical patients with haemophilia A and inhibitors in Spain. METHODS: A decision-analytic model was developed to estimate the cost to the Spanish National Health System of providing haemostatic coverage in this haemophilia population, with age distribution and average weight derived from the literature, and the annual number of surgeries (0.33 per patient) from local data. Drug costs were calculated from official ex-factory prices with a 7.5% mandatory deduction and recommended dosing regimens. RESULTS: The estimated average costs per patient were €10 100.73 (aPCC) and €14 265.89 (rFVIIa) for dental extraction, €24 043.88 (aPCC) and €62 301.08 (rFVIIa) for minor surgery and €126 595.81 (aPCC) and €347 731.09 (rFVIIa) for major surgery. Assuming an estimated 23 annual surgeries in this population (N = 69), distributed as 19% dental extraction, 50% minor surgery and 31% major surgery, the total annual cost of prophylaxis was €1 209 682.35 with aPCC and €3 221 929.28 with rFVIIa. CONCLUSIONS: aPCC costs were 62.5% lower than rFVIIa. Assuming potential clinical equivalence, aPCC is a potentially cost-saving option for surgical patients with haemophilia A and inhibitors.

Hindfoot malalignment in adults with haemophilic ankle arthropathy: The importance of early detection and orthotic treatment.

INTRODUCTION: Haemophilic arthropathy (osteoarthritis secondary to haemophilia) of the ankle may result in painful hindfoot malalignment. PURPOSE: To analyse hindfoot alignment in subjects with haemophilic arthropathy of the ankle and evaluate the response (improvement of pain, function and alignment) to the orthotic treatment prescribed in patients with malalignment. METHODS: The study included 163 patients with haemophilia, all of them over 16 years of age. Hindfoot alignment and footprint were analysed in patients with and without haemophilic arthropathy of the ankle (as determined by the Pettersson score). Response to the use of an orthosis was evaluated at 6 months by means of the AOFAS Ankle-Hindfoot Scale. RESULTS: Fifty-six (59.5%) patients with haemophilic arthropathy presented with concomitant  hindfoot malalignment. The most common abnormality was a valgus alignment combined with a neutral footprint. In 14 cases, valgus was associated with a pes planus or a pes cavus. Only 5 patients without haemophilic arthropathy (7.2%) presented with some form of malalignment. The differences between the groups were statistically significant. The probability of having malalignment increased with the degree of arthropathy. Patients with haemophilic arthropathy and malalignment were treated with an orthosis, with insoles as the most commonly used alternative (86%). Such treatment significantly improved patients' pain and function-related scores on the AOFAS Ankle-Hindfoot Scale. CONCLUSION: Given the high rates of valgus malalignment in subjects with haemophilic arthropathy of the ankle, and the good response rates obtained following individualised orthotic treatment, it seems reasonable to routinely evaluate hindfoot alignment in this group of patients.

Joint status in Spanish haemophilia B patients assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score.

AIM: The use of musculoskeletal ultrasound (MSK-US) following protocols for haemophilic arthropathy and the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score can help standardize monitoring in haemophilia. This study evaluated the joint status (elbows, knees and ankles) of patients with haemophilia B (HB) in Spain using MSK-US and the HEAD-US score. METHODS: Haemophilia B patients ≥14 years old were included in this observational, multicentre, cross-sectional study, regardless of their clinical condition, HB severity and treatment received. Two blinded observers were involved in image acquisition and scoring in each centre. RESULTS: Eighty-two patients from 12 centres were enrolled: 27% mild HB, 23% moderate, 50% severe HB. Mean age was 38.9 ± 16.4 years, 60% were treated on demand (OD) and 40% were on prophylaxis. HEAD-US was zero in all joints in 28.6% OD patients and 36.4% on prophylaxis. Mean scores significantly worsened with HB severity, except for the left knee. Patients on primary and secondary prophylaxis had significantly better joint health vs OD patients in all joints, except the right ankle. Among OD patients, those with severe disease presented significantly worse scores in all HEAD-US items related to permanent damage. CONCLUSION: Joint status of HB patients in Spain is influenced by severity and treatment modality, related to the development of arthropathy, which appears prevalent in OD patients with severe HB. Routine assessment with an imaging tool such as ultrasound and HEAD-US system may help to improve joint health by personalizing and adjusting treatment in this population.

Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial.

A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P< .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274.