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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.

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

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Background and Objectives Shortage of blood during the severe acute respiratory syndrome‐COV‐2 (SARs‐COV‐2) pandemic impacted transfusion practice. The primary aim of the study is to assess management of acute haemolytic crisis (AHC) in glucose‐6‐phosphate dehydrogenase(G6PD)‐ deficient children during SARs‐COV‐2 pandemic, and then to assess blood donation situation and the role of telemedicine in management. Methods Assessment of G6PD‐deficient children attending the Emergency Department (ER) with AHC from 1 March 2020 for 5 months in comparison to same period in the previous 2 years, in three paediatric haematology centres. AHC cases presenting with infection were tested for SARs‐COV‐2 using RT‐PCR. Children with Hb (50–65 g/L) and who were not transfused, were followed up using telemedicine with Hb re‐checked in 24 h. Results A 45% drop in ER visits due to G6PD deficiency‐related AHC during SARs‐COV‐2 pandemic in comparison to the previous 2 years was observed. 10% of patients presented with fever and all tested negative for COVID‐19 by RT‐PCR. 33% of patients had Hb

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.

Blood transfusion in sub-Saharan Africa (SSA) is at a crossroad. Significant recent developments may help meet local needs in safe blood products and fulfil a global health target, as highlighted by the World Health Organization (WHO) Millennium and Sustainable Development Goals, in improving supply and safety, and ensuring the gradual implementation of selective haemotherapy. When WHO recommended the evaluation of convalescent blood or plasma to treat Ebola-infected patients during the recent epidemics, substantial gaps in local blood collection, testing and technology infrastructure and safety, as compared to best accepted quality standards, became evident. This evidence should now serve as an 'electro-shock'/awakening call used to highlight the needs for local governments to support National Blood Transfusion Services and establish robust national regulatory authorities that are mandated to bear regulatory responsibilities of blood establishments. A nationally co-ordinated blood programme is the best tool to gather reliable epidemiological data, address local needs in blood and blood products and serve public health. A literature review using WHO website and PubMed was conducted in this article to outline the current clinical use of blood products and plasma derivatives in SSA. This text also intends to highlight the gaps to be filled in the coming years with respect to quality, safety, supply and efficacy of blood and plasma products, in line with WHO guidelines for transfusion.

In April 2017, a workshop sponsored by the National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources, and the Center for Translation Research and Implementation Science was held to discuss blood availability and transfusion safety in low- and middle-income countries (LMICs). The purpose of the workshop was to identify research opportunities for implementation science (IS) to improve the availability of safe blood and blood components and transfusion practices in LMICs. IS describes the late stages of the translational research spectrum and studies optimal and sustainable strategies to deliver proven-effective interventions. Regional working groups were formed to focus on opportunities and challenges in East Africa, Central/West Africa, Middle East and North Africa, Latin America and the Caribbean, Southeast Asia, Western Pacific Asia, Eastern Europe, and Central Asia. The need for an "adequate supply of safe blood" emerged as the major overriding theme. Among the regional working groups, common cross-cutting themes were evident. The majority of research questions, priorities, and strategies fell into the categories of blood availability, blood transfusion safety, appropriate use of blood, quality systems, health economics and budgeting, and training and education in IS. The workshop also brought into focus inadequate country-level data that can be used as the basis for IS initiatives. A mixed approach of needs assessment and targeted interventions with sufficient evidence base to move toward sustainment is an appropriate next step for blood availability and transfusion safety research in LMICs.

BACKGROUND Because there is a global shortage of intravenous immunoglobulin, there is a need for new products to fill the gap. STUDY DESIGN AND METHODS This was a multicenter, open-label study investigating the safety and efficacy of a newly developed mini-pool intravenous immunoglobulin G for children with immune thrombocytopenia. Seventy-two patients ages 1 to 18 years with newly diagnosed (

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Several biomaterials can be obtained from human blood. Some are used for clinical indications requiring a high content in fibrinogen, while others are used because they contain multiple platelet growth factors. Mimicking thrombin-induced physiological events of coagulation leading to fibrino-formation and platelet activation, blood biomaterials have critical advantages of being devoid of tissue necrotic effects and of being biodegradable by body enzymes. Fibrin-based biomaterials, known as fibrin glues or fibrin sealants, have been used for more than 30 years as surgical hemostatic and sealing agents, demonstrating benefits in essentially all surgical fields, including reconstructive plastic surgery and wound treatment. Clinical interest in platelet growth factor-rich biomaterials (often known as platelet gels or platelet-rich-plasma) has emerged more recently. Platelet gels are used in clinical situations to achieve wound healing and repair soft and hard tissues. Applications include the healing of recalcitrant ulcers and burns, and stimulation of osseous tissue regeneration in dentistry, implantology, and maxillofacial and plastic surgery. They were evaluated recently in knee osteoarthritis and for the repair of musculoskeletal tissue lesions in sports medicine. Platelet lysates are now used as a substitute for fetal bovine serum and for ex vivo clinical-scale expansion of stem cells, opening new perspectives in regenerative medicine. We present the scientific rationale that prevailed in the development of blood biomaterials, describe their modes of production and biochemical and functional characteristics, and present clinical applications in regenerative medicine.

Management of patients with inherited bleeding disorders (IBDs) showed remarkable advances during the last three decades. Safe plasma derived and recombinant clotting factor concentrates (CFCs) have available for prophylaxis therapy in patients with hemophilia with the aim to prevent or reduce bleeding episodes. This improved the quality of life of these patients and allowed them to be fully integrated in education and work like their non hemophiliac-peers. While this is true in the developed world, patients with IBDs living in developing world have limited access to safe CFCs. The high cost of CFCs prohibits its procurement by governments from these countries. As a consequence, patients suffer from complications of the disease as well as viral and immunological risks associated with the transfusion of fresh frozen plasma (FFP) or cryoprecipitate. Pathogen inactivation of FFP and cryoprecipitate at an affordable cost for developing countries can both increase safety of domestic plasma components as well as availability of safe treatment. A medical device for Solvent and Detergent Virus Inactivation of Cryoprecipitate was introduced into the market in 2010. The medical device was registered in Egypt in 2013. Since then, 285,250 units of cryoprecipitate were processed using these devices and helped to produce more than 32 million units of coagulation Factor VIII (FVIII) to treat more than 2000 patients with hemophilia A, von Willebrand Disease as well as other IBDs, like fibrinogen deficiency. The cost of a FVIII unit using the minipool technology was around 7 US cents which is lower than that from industrial cryoprecipitate (>14 US cents according to lowest price of FVIII concentrates in Egypt) and even much lower if compared to the mean cost of 21 US Cents for all types of CFCs according to procurement prices in Egypt as well. This supply strategy is now on going with the development of a medical device to produce local immunoglobulins for the treatment of immunodeficient patients.

Resume Le plasma pour transfusion, le cryoprecipite et le surnageant de cryoprecipite prepares par les etablissements de transfusion sanguine sont toujours utilises dans de nombreux pays, a la fois dans le monde en developpement comme dans celui industrialise, pour le traitement de differents troubles hemorragiques. En l’absence de procedes d’inactivation virale, ces fractions plasmatiques peuvent etre impliquees, et cela en depit de la mise en place de methodologies de depistage viral de plus en plus sophistiquees, dans des cas de transmissions de virus plasmatiques pathogenes, au premier rang desquels se trouvent le VIH et les virus des Hepatites B et C. Nous avons recemment adapte la methodologie d’inactivation virale industrielle par solvant–detergent (SD) pour son application a un traitement a petite echelle a l’aide d’un dispositif a usage unique. A ce titre, le procede peut donc etre utilise par les etablissements de transfusion, sans le recours a un centre de production industriel. Les etudes montrent que le procede conduit a une bonne recuperation de l’activite fonctionnelle des proteines plasmatiques, dont les facteurs de la coagulation (tels que le facteur VIII et le fibrinogene coagulable) et/ou les inhibiteurs de proteases (tel que l’alpha 2-antiplasmine). Les validations virales ont montre des facteurs de reduction superieur a 4,17, superieur a 4,73 et superieur a 4,72 logs pour les virus VIH, le virus de la diarrhee virale bovine (BVDV) et pseudorage (PRV), respectivement, en quelques minutes de traitement. Un dispositif permettant le traitement SD et l’elimination des agents d’inactivation virale est en cours de developpement pour permettre la standardisation dans l’application du procede par les etablissements de transfusion ou des centres de service nationaux ou regionaux.

BACKGROUND AND OBJECTIVES Major technical developments have been made in recent years to improve the quality and safety of human plasma for transfusion and fractionation. The present study was performed to assess, for the first time, the feasibility of applying a nanofiltration process, using 75-nm and 35-nm mean pore size membranes (Planova) 75N and Planova 35N), to human plasma. MATERIALS AND METHODS Ten apheresis plasma units were obtained from 10 plasma donors. Within 4 h of collection, plasma was subjected to leucoreduction and filtration (using 75-nm and 35-nm mean pore size membranes) at 35 degrees C, at less than 1 bar pressure. Aliquots of plasma were taken at all steps of the filtration procedure and numerous plasma quality parameters were measured. In addition, six hepatitis C virus (HCV)-positive plasma donations were experimentally subjected to the same filtration sequence and subsequently assessed by RNA polymerase chain reaction (PCR) and branched-chain DNA-quantification assays. RESULTS Leucoreduced plasma can be reproducibly nanofiltered onto a sequence of 75-nm and 35-nm membranes, at a flow rate of 450 ml/h and a temperature of 35 +/- 0.5 degrees C. Some protein dilution, or loss, was found during filtration, but the plasma filtered through membranes with a mean pore size of 75 nm and 35 nm met in vitro specifications for use in transfusion or fractionation. There were no signs of activation of the coagulation system. HCV-positive plasma donations became negative, as judged by PCR and branched-chain DNA assay results, after filtration through the 35-nm membrane. CONCLUSIONS It is possible to apply a 75 + 35-nm filtration process to leucoreduced human plasma. This technology may have important future benefits in improving the quality and safety of plasma, by removing blood cell debris and infectious agents.

von Willebrand disease (VWD) is frequently ignored as a cause of menorrhagia. We investigated Egyptian women complaining of heavy menstrual bleeding (HMB) and/or other bleeding symptoms to detect potential VWD cases. Seventy-five female patients complaining of HMB and/or bleeding symptoms and 38 age-matched healthy female controls went through a family history questionnaire, a physical examination and were evaluated for bleeding score, pictorial blood assessment chart (PBAC), complete blood count, serum ferritin, blood group, prothrombin time, activated partial thromboplastin time, factor VIII (FVIII) activity, von Willebrand factor (VWF) ristocetin cofactor (RCo) activity, antigen (Ag), and RCo/Ag ratio. Sixty-eight of 75 patients presented with HMB, out of which 46 had no organic pathology and 7 presented other bleeding symptoms. Six patients were diagnosed with VWD, three with HMB, two with other bleeding symptoms and one with family history of VWD. Two related VWD patients were diagnosed in the control group. There were significant differences in bleeding and PBAC scores, ferritin level, FVIII activity, VWF:RCo and VWF:Ag between VWD patients and controls. This study indicated a high prevalence of VWD among patients with HMB without organic pathology (6.5%) and demonstrated the sensitivity of diagnostic parameters of VWD patients in an outreach campaign. The inexpensive bleeding and PBAC scoring systems are valuable to exclude cases without objective bleeding symptoms. Raising gynaecologists awareness about hereditary bleeding disorders is important to ensure a proper diagnosis and possible referral of these patients. Management of these patients with comprehensive medical care services under a multidisciplinary team would be ideal.

Background Thrombotic thrombocytopaenic purpura (TTP) is a rare life-threatening disease. Plasma exchange has significantly decreased the mortality from this disease, which still tends to recur in a substantial proportion of patients. This study describes the clinical spectrum and response to treatment and explores the risks of relapse in a cohort of patients. Methods Patients treated for TTP at the Clinical Haematology Unit, Cairo University, Egypt, between 2000 and 2008 were identified. Complete demographic, clinical history and full clinical examination, laboratory, treatment modalities and duration, and outcome data were collected and analysed. The follow-up duration was 24 months. Results 30 patients; 13 men (43%) and 17 women (57%) with a median age of 42 years were treated for 46 episodes of TTP. The median duration of disease onset to diagnosis for the first episode was 7 days. Twenty-three patients (76.66%) were diagnosed as idiopathic primary and seven patients (23.33%) were secondary TTP. Four patients died during the first 24 h. Of the 26 patients, 22 (85.6%) achieved remission with an average of 7.55 plasma exchange sessions, Another nine patients had 25 relapses (mean 2.7). Splenectomy was performed in three patients (11.5%). The 24-month overall survival was 80%. The initial low platelet count and high LDH were the only two statistically significant relapse predictors. Conclusions The current results conform to the reported literature on the outcome of TTP. The very early mortality due to late referral highlights the need of education about the disease among primary healthcare providers.

Solvent-detergent (S/D) viral inactivation was recently adapted to the treatment of single plasma donations and cryoprecipitate minipools. We present here a new process and a new bag system where the S/D reagents are removed by filtration and the final products subjected to bacterial (0.2 microm) filtration. Recovered and apheresis plasma for transfusion (FFP) and cryoprecipitate minipools (400 +/- 20 mL) were subjected to double-stage S/D viral inactivation, followed by one oil extraction and a filtration on a S/D and phthalate [di(2-ethylhexyl) phthalate (DEHP)] adsorption device and a 0.2 microm filter. The initial and the final products were compared for visual appearance, blood cell count and cell markers, proteins functional activity, von Willebrand factor (VWF) multimers and protein profile by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Tri (n-butyl) phosphate (TnBP) was quantified by gas chromatography and Triton X-45 and DEHP by high-performance-liquid chromatography (HPLC). General safety tests were by 6.5 mL/kg intravenous injection in rats. The treated plasmas and cryoprecipitates were very clear and the protein content and functionality, VWF multimers and SDS-PAGE profiles were well preserved. TnBP and Triton X-45 were < 1 and

Cryoprecipitate is still used to treat factor VIII (FVIII), von Willebrand factor (VWF) and/or fibrinogen deficiency. Recently a solvent-detergent (S/D) process of minipools of cryoprecipitate performed in a closed bag system has been designed to improve its viral safety. Still, cryoprecipitate has other drawbacks, including low concentration in active proteins, and presence of haemolytic isoagglutinins. We report here the biochemical evaluation of S/D-treated minipools of cryoprecipitates depleted of cryo-poor plasma. Cryoprecipitates were solubilized by 8 mL of a sterile glucose/saline solution, pooled in batches of 40 donations and subjected to S/D treatment in a plastic bag system using either 2% TnBP or 1% TnBP-1%Triton X-45, followed by oil extractions (n = 10). Mean (+/-SD) FVIII and fibrinogen content was 8.86 (+/-1.29) IU mL(-1) and 16.02 (+/-1.98) mg mL(-1), and 8.92 (+/-1.05) IU mL(-1) in cryoprecipitate minipools treated with 2% TnBP, and 17.26 (+/-1.71) mg mL(-1), in those treated by TnBP-Triton X-45, respectively. The WWF antigen, ristocetin cofactor and collagen binding activities were close to 10, 7 and 8 IU mL(-1), respectively, and were not affected by either SD treatment. VWF multimeric pattern of SD-treated cryoprecipitates were similar to that of normal plasma, and the >15 mers and >10 mers content was identical to that of the starting cryoprecipitates. The anti-A and anti-B titre was 0-1 and 0-1/8, respectively. Therefore, it is possible to prepare virally inactivated cryoprecipitate minipools depleted of isoagglutinins and enriched in functional FVIII, VWF and clottable fibrinogen.

Background Solvent/detergent (S/D) inactivates enveloped viruses in plasma. The current technology requires a plasma fractionation facility and is applied to large plasma pools, which increases the cost and risks of exposure to S/D-resistant pathogens and lowers the content of protein S and alpha2-antiplasmin. Two S/D treatment procedures for single donations or minipools of plasma have been developed with a single-use bag system. Study design and methods Frozen plasma samples were thawed and treated in disposable bags with either 2 percent tri(n-butyl)phosphate (TnBP) at 37 degrees C or 1 percent TnBP and 1 percent Triton X-45 at 31 degrees C for 4 hours. Plasma samples were extracted three times with 7.5 percent sterile castor oil to remove TnBP and Triton X-45. The TnBP-treated plasma samples were further subjected to a clarifying centrifugation (3800 x g, 30 min). Final plasma samples were dispensed into individual bags and frozen at -30 degrees C. Plasma quality was assessed at each step of the procedures. Results Both processes yielded greater than 90 percent mean recovery of coagulation factors (clottable fibrinogen, von Willebrand factor, and factors VIII, V, VII, IX, X, and XI), anticoagulants (protein C, protein S), protease inhibitors (antithrombin, alpha2-antiplasmin), total protein, albumin, and immunoglobulins. Global coagulation tests of the treated plasma samples were normal. Final TnBP and Triton X-45 content was less than 10 and 50 ppm, respectively. Conclusion S/D treatment of plasma can be performed in a closed-bag system under conditions that maintain plasma protein quality. The technology is simple, presents advantages over the industrial large-scale S/D plasma process, and could be performed in blood centers.

Background and Objectives Single-donor or small-pool cryoprecipitates are produced by blood establishments, mostly in developing countries, for substitute therapy in haemophilia A, von Willebrand disease and fibrinogen deficiency, as well as for the manufacture of fibrin sealant. As cryoprecipitate may be contaminated with pathogenic plasma-borne viruses, there is an urgent need to develop a simple method for the viral inactivation of cryoprecipitate. Materials and Methods Cryoprecipitate was obtained according to standard procedures. Ten minipools of five or six donations of cryoprecipitate were prepared and subjected, in sterile closed bags, to a viral inactivation treatment using either 2% tri(n-)butyl phosphate (TnBP) for 4 h at 37 °C or the combination of 1% TnBP and 1% Triton X-45 for 4 h at 31 °C. The cryoprecipitates were subsequently extracted three times in their processing bags by mixing and decantation using 7·5% sterile ricinus oil. The TnBP-treated cryoprecipitates were further subjected to a clarifying centrifugation step at 3800 g for 30 min. The final products were dispensed into individual bags and frozen at −30 °C or lower. Results The cryoprecipitates treated with either 2% TnBP or 1% TnBP + 1% Triton X-45 showed excellent (> 93%) mean recovery of coagulant factor VIII (FVIII), ristocetin cofactor Von Willebrand factor (VWF:RCo), and clottable fibrinogen activity. Prothrombin time, international normalized ratio and activated partial thromboplastin time increased during solvent–detergent treatment but returned to initial values after oil extractions. The final content of TnBP and Triton X-45 was