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Background: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile. Treatment goals: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care. These outcomes also do not address the complexity of health‐related quality of life impacted by haemophilia and its treatment. Conclusion: Capitalizing on the major potential of therapeutic innovations, 'Normalization' of haemostasis, as a concept, should include the aspiration of enabling individuals to live as normal a life as possible, free from haemophilia‐imposed limitations. To achieve this—being supported by the data reviewed in this manuscript—the concept of haemostatic and life Normalization needs to be explored and debated within the wider multidisciplinary teams and haemophilia community. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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 111In‐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 111In‐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. [ABSTRACT FROM AUTHOR]

Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to increased destruction and reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document that had been launched in 2011. The updated guidelines have been the reference for the diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have updated the main recommendations appropriately. Our aim is to provide a practical tool to facilitate the integral management of all aspects of primary ITP management. [ABSTRACT FROM AUTHOR]

The first three recommendations, based on the use of a validated bleeding assessment tool[7] (BAT) for diagnosis, endorsed this mechanism only for patients with a low probability of VWD (e.g., primary care [PC] setting). Keywords: 2021 guidelines; diagnosis; survey; von Willebrand disease; von Willebrand factor EN 2021 guidelines diagnosis survey von Willebrand disease von Willebrand factor 925 927 3 05/19/23 20230501 NES 230501 Von Willebrand disease (VWD) is the coagulopathy with more under-, over- and misdiagnosis due to its challenging diagnosis.[1] To improve care for people with VWD, in 2021 the American Society of Haematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Haemophilia Foundation (NHF) and the World Federation of Haemophilia (WFH) published guidelines on the diagnosis[2] and management[3] of VWD. On the other hand, in the case of a patient with a normal bleeding scale result or no assessment scales performed in the centre, 71% of the specialist would not expand the patient study to rule out VWD, while the remaining 29% would directly perform blood laboratory tests. [Extracted from the article]

Acquired haemophilia A (AHA) is a rare severe bleeding disorder resulting from the production of autoantibodies directed against coagulation factor VIII. At presentation, bleeding events can be severe, and an early diagnosis and treatment are of major importance. The current study aims to analyse the treated patients who have been diagnosed with AHA for a better understanding of our population and treatment outcome. We conducted a retrospective study with 26 patients who had been diagnosed with AHA and who were treated in our hospital between January 2006 and January 2021. The patients ranged in age from 30 to 85 years old: 46.10% were men, 46.10% had no known underlying condition, 27% had an underlying malignancy, 7.60% presented with other diseases: psoriatic arthritis and Paget's disease, and 19.30% presented with AHA during puerperium. All of the patients had bleeding events and were treated with bypass agents for this as well as with immunosuppressive therapy to eradicate the inhibitor. A total of 53.80% of the patients had major bleeding. Sixty-nine percent of the patients achieved complete remission, but 26.90% died during the follow-up, although bleeding was not the cause of death in any of these cases. Our observations underline the importance of clinical suspicion and early referral to centres with experience and laboratory facilities for managing AHA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Care for children with haemophilia during COVID-19: Data of the PedNet study group COVID-19 and telemedicine in haemophilia in a patient with severe haemophilia a and orthopaedic surgery. Keywords: children care; COVID-19; haemophilia; telemedicine EN children care COVID-19 haemophilia telemedicine e537 e539 3 07/21/21 20210701 NES 210701 DATA AVAILABILITY STATEMENT Data available on request from the authors. Regular prophylactic treatment could continue in haemophilia patients in the epicentre of the pandemic Wuhan, China.4 In the HTCs connected to PedNet, this was also the case. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

COVID-19 and telemedicine in haemophilia in a patient with severe haemophilia A and orthopaedic surgery Keywords: COVID-19; haemophilia A; orthopedic; surgery; telemedicine EN COVID-19 haemophilia A orthopedic surgery telemedicine e137 e139 3 02/04/21 20210101 NES 210101 We describe the case of a patient with severe haemophilia A who underwent major orthopaedic surgery managed postoperatively by telemedicine (TM). At that moment, given the progression of the pandemic, the Orthopaedic Surgery Department wards would be handed over to care for COVID-19 patients, at that point 80% occupied by such patients. From the very beginning of the health crisis, our hospital housed a large number of COVID-19 patients, forcing us to set up TM programmes to manage haemophilia patients safely. [Extracted from the article]

ABSTRACT Objectives Methods Results Conclusions The 24‐month, prospective, non‐interventional, European multicenter A‐SURE study evaluated the real‐world effectiveness of prophylaxis using an extended half‐life recombinant factor VIII (FVIII) Fc fusion protein, efmoroctocog alfa (hereinafter rFVIIIFc), compared with prophylaxis using standard half‐life (SHL) FVIII products in patients with hemophilia A.Primary endpoints were annualized bleeding rate (ABR), annualized injection frequency, and annualized factor consumption. A comparative study design unique for an observational hemophilia study was implemented to reduce potential confounding in effectiveness estimates, wherein each patient prescribed rFVIIIFc was matched with one receiving SHL FVIII. Propensity scores were used for adjustment in statistical analyses.Outcomes for all primary endpoints were significantly better in the rFVIIIFc group (n = 184) compared with the SHL FVIII group (n = 170): mean ABR 1.5 versus 2.3 (difference of −0.8; p = 0.0147); mean annualized injection frequency 114.4 versus 169.2 (difference of −54.8; p < 0.0001); and mean annualized factor consumption 243 024.2 versus 288 718.6 International Units (difference of 45 694.5; p = 0.0003). rFVIIIFc was well tolerated, with no inhibitor development.rFVIIIFc has superior prophylactic effectiveness versus SHL FVIII, providing higher bleed protection with fewer injections and lower factor consumption. [ABSTRACT FROM AUTHOR]

Loss of sialic acid from the carbohydrate side chains of platelet glycoproteins can affect platelet clearance, a proposed mechanism involved in the etiopathogenesis of immune thrombocytopaenia (ITP). We aimed to assess whether changes in platelet glycosylation in patients with ITP affected platelet counts, function, and apoptosis. This observational, prospective, and transversal study included 82 patients with chronic primary ITP and 115 healthy controls. We measured platelet activation markers and assayed platelet glycosylation and caspase activity, analysing samples using flow cytometry. Platelets from patients with ITP with a platelet count <30 × 103/µL presented less sialic acid. Levels of α1,6-fucose (a glycan residue that can directly regulate antibody-dependent cellular cytotoxicity) and α-mannose (which can be recognised by mannose-binding-lectin and activate the complement pathway) were increased in the platelets from these patients. Platelet surface exposure of other glycoside residues due to sialic acid loss inversely correlated with platelet count and the ability to be activated. Moreover, loss of sialic acid induced the ingestion of platelets by human hepatome HepG2 cells. Changes in glycoside composition of glycoproteins on the platelets' surface impaired their functional capacity and increased their apoptosis. These changes in platelet glycoside residues appeared to be related to ITP severity. [ABSTRACT FROM AUTHOR]

We aimed to identify the key players in the prothrombotic profile of patients with systemic lupus erythematosus (SLE) not mediated by antiphospholipid antibodies, as well as the potential utility of global coagulation tests to characterize hemostasis in these patients. Patients with SLE without antiphospholipid antibodies and without signs of thrombosis were included. The kinetics of clot formation were determined by ROTEM®. Platelet activation markers were determined by flow cytometry. Thrombin generation associated with Neutrophil Extracellular Traps (NETs) and microparticles (MPs) was measured by calibrated automated thrombogram (CAT). The plasma levels of PAI-1 were also determined. ROTEM® showed a procoagulant profile in SLE patients. SLE patients had activated platelets and more leukocyte/platelet aggregates at basal conditions. The plasma PAI-1 and platelet aggregates correlated with several ROTEM® parameters. The thrombin generation associated withthe tissue factor (TF) content of MPs and with NETs was increased. Our results suggest the utility of global tests for studying hemostasis in SLE patients because they detect their procoagulant profile, despite having had neither antiphospholipid antibodies nor any previous thrombotic event. A global appraisal of hemostasis should, if possible, be incorporated into clinical practice to detect the risk of a thrombotic event in patients with SLE and to consequently act to prevent its occurrence. [ABSTRACT FROM AUTHOR]