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Introduction: Recent guidelines for von Willebrand Disease (VWD) highlighted the challenges in diagnosis and management. Identifying the number of persons with VWD (PwVWD) internationally will help target support to aid diagnosis of PwVWD., Aim: To examine international registration rates of PwVWD, the influence of income status, geographical region and the age and sex profile. Cumulatively, these data will be used to inform future strategy from the World Federation of Haemophilia (WFH) to address unmet clinical and research needs., Methods: Data from the 2018/2019 WFH Annual Global Survey (AGS) were analysed, providing a global perspective on VWD registration., Results: Registration rates are lowest in South Asia (0.6/million population) and highest in Europe/Central Asia (50.9/million population, 0.005%), but below the expected prevalence rate (0.1%). National economic status impacted VWD registration rates, reflecting variation in access to optimal healthcare infrastructure. Females represented the majority of PwVWD globally, however, in low-income countries (LIC) males predominated. Age profile varied, with markedly higher rates of paediatric registrations in North America, Middle East and North Africa and South Asia. Rates of type 3 VWD registrations were significantly influenced by economic status (81% of VWD diagnoses in LIC), suggesting only the most severe VWD types are diagnosed in resource limited settings., Conclusion: Significant variation in registration rates of PwVWD exist internationally and is influenced by income status and the presence of HTC networks. Improved understanding of registration rates will enable targeting of advocacy to improve awareness, diagnosis and support for PwVWD internationally., Key Points: Registration rates of People with Von Willebrand Disease (PwVWD) vary internationally and are influenced by national income status Although females represent the majority of PwVWD globally, in low income countries (LIC) males predominated, possibly related to stigma surrounding gynaecological bleeding. Rates of type 3 VWD registration were significantly influenced by economic status (81% of VWD diagnoses in LIC), suggesting only the most severe VWD types are diagnosed in resource limited settings., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Highly effective treatment of haemophilia A and B is primarily available to 15% of the world's population, in high-income countries. In low-income countries (LICs) and lower-middle-income countries (LMICs), morbidity and mortality are high because of greatly reduced access to diagnosis, care, and treatment. We report the challenges and impact after the first 5 years (mid-2015-2020) of the expanded World Federation of Hemophilia (WFH) Humanitarian Aid Program (HAP). WFH HAP donated coagulation products were used to treat more than 250 000 acute bleeding episodes, manage approximately 4000 surgeries, and establish bleeding preventive prophylaxis in about 2000 patients in 73 countries. Health-care providers worldwide learned optimal management of patients with complex needs through virtual and in-person training. In response to the programme, some governments increased investment in haemophilia care, including independent purchases of small amounts of treatment products. With unparalleled scope and complexity, and substantial benefits to people with haemophilia and society in general, the WFH HAP is an exemplar of partnership between for-profit and not-for-profit organisations advancing health-care equity in LICs and LMICs, which could be replicated by other organisations supporting people with different monogenic diseases., Competing Interests: Declaration of interests RK has received research funding paid to his institution from the Bayer Hemophilia Awards Program. GFP is the Vice President Medical of the WFH and a member of the medical and scientific advisory board for the National Hemophilia Foundation (NHF). SWP has received consulting fees paid to himself or his institution (University of Michigan, Michigan, MI, USA) from ApcinteX, ASC Therapeutics, Bayer, BioMarin Pharmaceutical, Catalyst Biosciences, CSL Behring, GenVentiv Therapeutics, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron and Intellia (jointly), Roche and Genentech (jointly), Sangamo Therapeutics, Sanofi, Takeda Pharmaceutical, Spark Therapeutics, and uniQure. FR has received consulting fees from Roche, European Haemophilia Consortium, NHF, WFH, and the American Thrombosis and Hemostasis Network. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Immune Tolerance Induction (ITI) is the first-choice therapy to eradicate Factor VIII (FVIII) neutralizing antibodies in patients with haemophilia A (HA). There is limited published data on ITI from East Mediterranean countries., Aim: To assess the effectiveness of a low-dose ITI regimen to eradicate FVIII neutralizing antibodies in children with severe HA and high-titre inhibitors., Methods: A prospective, single-arm study was conducted in children with HA (FVIII < 1 IU/dl), high-titre inhibitors and poor prognostic factors for successful ITI. Patients were treated with ∼50 IU/kg plasma-derived FVIII containing von Willebrand factor (pdFVIII/VWF) concentrate (Koate-DVI, Grifols) three times a week. Time to achieve tolerance, total and partial success were analysed after ITI. Annual bleeding rate (ABR), number of target joints, FVIII recovery and school absence were compared before and after ITI., Results: Twenty patients with median (range) age of 6.2 (3-12) years and pre-ITI inhibitor titre of 36.5 (12-169) BU were enrolled. ITI lasted ≤12 months (early tolerization) in 45% of patients. Median follow-up was 12 months (3-22) and total response rate was 80% (60% total success; 20% partial success). Patients with two and three poor prognosis factors achieved overall success rate of 60% and 50%, respectively. ABR, target joints and school absence were reduced after ITI by 60%, 50% and 44.1%, respectively. In successful ITI tolerized patients, FVIII recovery was 90 (60-100)%., Conclusion: A low-dose ITI therapy using a pdFVIII/VWF concentrate achieved at least partial tolerance in 80% of patients, and reduced annual bleeds in children with high inhibitor titres and at least one poor prognosis factor for ITI treatment success., (© 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Background: Patients with hemophilia (PWH) might need surgical interventions during the course of their lives. Such medical interventions pose hemostatic challenges and requests infusion of clotting factor concentrates (CFCs) during peri and postoperative for variable periods to prevent bleeding and until complete wound healing. Access to CFCs to PWH living in resource limited settings is usually a challenge which makes surgical interventions either risky or not practical. Recently World Federation of Hemophilia (WFH) started a humanitarian aid program to channel CFCs into resource limited countries and which allowed the possibility to perform surgical interventions for PWH in these countries., Aim of Work: To study safety and efficacy of using lower doses of CFCs for surgical prophylaxis., Methods: Review of literature and our center experience to demonstrate safety and efficacy of low dose surgical prophylaxis using CFCs RESULTS: Several elements can help using lower doses of CFCs for surgical prophylaxis in resource limited setting. These elements include severity of hemophilia, type of surgical procedure, the use of hemostatic surgical techniques, the type of CFCs, the mode of infusion of CFCs and finally the use of adjunctive therapies CONCLUSION: Management of surgical procedures for PWH in a multidisciplinary specialized hemophilia treatment centers with proper understanding of hemostatic and surgical challenges of the procedure can allow for safe and effective use of lower doses of CFCs for surgical prophylaxis., (© 2019 John Wiley & Sons Ltd.)

Introduction: The gaps in haemophilia treatment around the world are enormous; approximately 60% of an estimated 475 000 individuals are not identified. Of the 187 000 diagnosed, 30% (57 000) access clotting factor replacement therapy. Since 1996, humanitarian aid distributed by the World Federation of Hemophilia (WFH) has played a minor, yet vital role providing life-saving clotting factor to countries in emergency situations. Donated amounts have been small and sporadic, often salvaging short-dated products, providing little opportunity to leverage donations with governments. In 2015, a prospective donation programme of 100 million I.U. per year of extended half-life factor VIII and IX over 10 years was established, necessitating the development of new logistics and training programmes by WFH., Aim: To measure the impact of a greatly expanded haemophilia humanitarian aid program., Materials and Methods: In 2016, the first full year of the expanded programme, WFH, distributed products to 58 countries with factor VIII usage <1 I.U. per capita, a level incompatible with long-term survival and far below the 4 I.U. FVIII per capita minimum established in Europe., Results: The scope of the programme and utilization data for 2016 indicate primarily use for acute bleeding, orthopaedic and emergency surgeries. Compared to 2014, 2016 data showed substantial increases in patients served (5.9-fold, from 2119 to 14 579), surgeries performed (37-fold) and bleeds treated (6.9-fold). Patients on prophylaxis rose from 0 to 852, including 458 children under 10 years old., Discussion: The expanded humanitarian aid programme impacts an estimated 10% of individuals with haemophilia previously unable to access treatment., Conclusion: This programme represents an unprecedented public-private partnership to deliver medicines to individuals with no access. Further, the programme offers the prospective opportunity to engage governments to take more responsiblity for increasing training, medical management, and product supply in 58 resource constrained countries., (© 2018 The Authors. Haemophilia Published by John Wiley & Sons Ltd.)

Eighteen cryoprecipitate minipools, each made of 30 units of low volume, concentrated cryoprecipitate, have been treated by solvent-detergent and filtration (S/D-F) in a single-use CE-marked bag system. The S/D-F cryoprecipitate contained a mean of 10.5 IU mL⁻¹ factor VIII (FVIII), 17 mg mL⁻¹ clottable fibrinogen, and >10 IU mL⁻¹ von Willebrand factor ristocetin co-factor, and anti-A and anti-B isoagglutinins were undetectable. The products have been infused in 11 severe (FVIII <1%) haemophilia A patients (mean age: 17.4 years; mean weight: 57.6 kg) at a dose close to 40 IU kg⁻¹. Patients were hospitalized for at least 36 h to determine FVIII recovery, half-life and clearance. They were also closely monitored for possible adverse events. None of the infused patients demonstrated reactions or adverse events even though they did not receive anti-allergic drugs or corticosteroids prior to infusion. The mean recovery of FVIII 10 min postinfusion was 69.7%. Mean FVIII half-life was 14.2 h and clearance was 2.6 mL h⁻¹ kg⁻¹. All patients had a bleeding-free interval of 8-10 days postS/D-F cryoprecipitate infusion. The data show that S/D-F cryoprecipitate FVIII presents a normal pharmacokinetics profile, and support that it could be safely used for the control of acute and chronic bleeding episodes in haemophilia A patients., (© 2011 Blackwell Publishing Ltd.)