Transfusion of blood components in pediatric age groups: an evidence-based clinical practice guideline adapted for the use in Egypt using 'Adapted ADAPTE'.

Pediatric transfusion is a complex area of medicine covering a wide age range, from neonates to young adults. Compared to adult practice, there is a relative lack of high-quality research to inform evidence-based guidelines. We aimed to adapt the pre-existing high-quality practice guidelines for the transfusion of blood components in different pediatric age groups to be available for national use by general practitioners, pediatricians, and other health care professionals. The guideline panel included 17 key leaders from different Egyptian institutions. The panel used the Adapted ADAPTE methodology. The panel prioritized the health questions and recommendations according to their importance for clinicians and patients. The procedure included searching for existing guidelines, quality appraisal, and adaptation of the recommendations to the target context of use. The guideline covered all important aspects of the indications, dosing, and administration of packed red cells, platelets, and fresh frozen plasma. It also included transfusion in special situations, e.g., chronic hemolytic anemia and aplastic anemia, management of massive blood loss, malignancies, surgery, recommendations for safe transfusion practices, and recommendations for modifications of cellular blood components. The final version of the adapted clinical practice guideline (CPG) has been made after a thorough review by an external review panel and was guided by their official recommendations and modifications. A set of implementation tools included algorithms, tables, and flow charts to aid decision-making in practice. This adapted guideline serves as a tool for safe transfusion practices in different pediatric age groups.

Challenges associated with access to plasma-derived medicinal products in low middle-income and low-income countries.

BACKGROUND AND OBJECTIVES: Plasma-derived medicinal products (PDMPs) are essential to treat many chronic conditions such as haemophilia and primary immunodeficiency. Patients living in low middle-income and low-income countries (LMICs and LICs, respectively) have limited access to PDMPs. The aim of this article is to explore the challenges of accessing PDMPs in LMICs and LICs. MATERIALS AND METHODS: A review of the literature and reports on blood safety, plasma production and its utilization to produce PDMPs in LMICs and LICs was carried out. RESULTS: There is huge wastage of recovered plasma in LMICs and LICs as a result of a lack of good manufacturing practice (GMP) in the production of plasma for fractionation. Together with the high cost of imported PDMP procurement, patients have limited access to such products. CONCLUSION: There is a need to improve the situation by using domestically sourced plasma through the initiation of local plasma programmes through a stepwise approach to improve access to PDMPs in LMICs and LICs.

Von Willebrand Disease: Gaining a global perspective.

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.

Transfusion medicine research in Africa: Insights from investigators in the field.

BACKGROUND AND OBJECTIVES: Research in low-resource settings is inherently challenging. We sought to assess the factors that have impeded or facilitated transfusion medicine (TM) research in various African settings. MATERIALS AND METHODS: A qualitative case study was conducted of selected investigators in Africa; selection was based on productivity-spanning publication, leadership and research in TM. We designed a questionnaire to explore the factors impeding or facilitating TM research to understand the impact on the investigators' careers. Written responses were independently coded and double-checked for precision. Qualitative analysis was conducted, whereby responses were grouped thematically and clustered by relationship. The initial findings were discussed with respondents to validate and refine the interpretations. The recorded transcript was analysed and incorporated into the final analysis. RESULTS: Six investigators participated in the study. Their responses yielded 471 coded comments: 389 from the questionnaires and 82 from the ensuing discussion. The most frequently cited factors described included knowledge and intellectual abilities (n = 104), personal effectiveness (n = 99), research and governance structure (n = 97), and engagement, influence and impact (n = 75). Four relationship clusters emerged from the facilitators (n = 42), barriers (n = 28), and common approaches (n = 26) to research, informing summary themes of adaptation, collaboration, perseverance, and resiliency. CONCLUSION: Individual attributes were found to be central to a successful TM research career in African settings. However, given other public health priorities and constraints, interpersonal relationships, organizational structures and the broader research context were important to TM researchers. Overcoming complexities demands adaptation, collaboration, perseverance and resiliency.

Low-dose immune tolerance induction therapy in children of Arab descent with severe haemophilia A, high inhibitor titres and poor prognostic factors for immune tolerance induction treatment success.

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.

Management of children with glucose-6-phosphate dehydrogenase deficiency presenting with acute haemolytic crisis during the SARs-COV-2 pandemic.

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 < 50 g/L and were all transfused. 50% had Hb between 50 and 65 g/L, half of them (n = 49) did not receive transfusion and only two patients (4%) required transfusion upon follow up. A restrictive transfusion strategy was adopted and one of the reasons was a 39% drop in blood donation in participating centres. CONCLUSION: Fewer G6PD-deficient children with AHC visited the ER during SARs-COV-2 and most tolerated lower Hb levels. Telemedicine was an efficient tool to support their families. A restrictive transfusion strategy was clear in this study.

Low-dose surgical prophylaxis: Optimization of use of World Federation of Hemophilia Humanitarian Aid donated clotting factor concentrates to developing countries.

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.

Addressing gaps in international blood availability and transfusion safety in low- and middle-income countries: a NHLBI workshop.

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.

Blood transfusion in sub-Saharan Africa: understanding the missing gap and responding to present and future challenges.

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.

A randomized multicenter study: safety and efficacy of mini-pool intravenous immunoglobulin versus standard immunoglobulin in children aged 1-18 years with immune thrombocytopenia.

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 (<1 month) immune thrombocytopenia who had platelet counts from 5 to 20 × 109 /L with no serious bleeding were recruited from four centers in Egypt. Eligible patients were randomized into three groups 1:1:1. Group A (n = 24) received blood group-specific mini-pool intravenous immunoglobulin in a dose equivalent to immunoglobulin 1 g/kg over 6 to 8 hours, Group B (n = 24) received standard intravenous immunoglobulin (approximately 1g/kg) as a single dose, and Group C (n = 24) did not receive any platelet-enhancing therapy. Parents signed informed consent. RESULTS: Of the patients who received mini-pool intravenous immunoglobulin, 14 achieved a complete response (CR) (58.8%), and four had a response (16.6%). Of the patients who received intravenous immunoglobulin G, 16 achieved a complete response (66.6%), and four had a response (16.6%). In Group C, eight patients achieved a complete response (33.3%), and four had a response (16.6%). The median time to response was 8, 9, and 21 days in Group A, B, and C, respectively, which was significantly higher in Group C than Groups A and B (p < 0.001). Patients in Groups A and B reported 16 adverse drug reactions. CONCLUSION: Mini-pool intravenous immunoglobulin G was well tolerated, presented no safety issues, and was effective in the treatment of immune thrombocytopenia, with efficacy comparable to that of the standard intravenous immunoglobulin G group, and it was significantly more effective than no treatment.

Viremia levels in hepatitis C infection among Egyptian blood donors and implications for transmission risk with different screening scenarios.

BACKGROUND: Knowledge about the viral load (VL) distributions in different stages of hepatitis C virus (HCV) infection is essential to compare the efficacy of serologic screening and nucleic acid testing (NAT) in preventing transfusion transmission risk. We studied HCV-RNA levels in Egyptian blood donors in the preseroconversion window period (WP) and in later anti-HCV-positive stages of infection. STUDY DESIGN AND METHODS: Subsets of individual-donation (ID)-NAT and anti-HCV-yield samples from a screening study among 119,756 donors were tested for VL by quantitative polymerase chain reaction (qPCR). Low viremia levels below the quantification limit of qPCR were determined by probit analysis using the proportion of reactive results on replicate NATs. Poisson distribution statistics were used to estimate transmission risk in different stages of HCV infection based on 50% minimum infectious doses (MID50 ) of 3.2 (1-10) and 316 (100-1000) virions in the absence and presence of anti-HCV, respectively. RESULTS: Rates of total HCV infections and WP-NAT-yield donations in two Egyptian blood centers varied between 2.6% to 4.5% and 1:3100 to 1:9500, respectively. VLs ranged from 82 to 3 × 10(7) copies/mL in WP and from fewer than 1600 to 1.6 × 10(6) copies/mL in anti-HCV-positive carrier donations. Only two (1.1%) of 175 donors with probable resolved infection had detectable RNA on replicate testing (estimated VLs of 0.5 and 1.8 copies/mL). This translates to an estimated transmission risk of 0.028% if ID-NAT-nonreactive, anti-HCV-positive donations would be used for RBC transfusions. CONCLUSION: Almost 99% of anti-HCV-reactive donations without detectable HCV-RNA on initial ID-NAT screening had eradicated the virus from the circulation, while 1% had extremely low VLs and are likely not infectious. The incremental safety offered by serologic testing of ID-NAT-screened blood seems minimal.

Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress.

Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis.

External financial aid to blood transfusion services in sub-Saharan Africa: a need for reflection.

Jean-Pierre Allain and colleagues argue that, while unintended, the foreign aid provided for blood transfusion services in sub-Saharan Africa has resulted in serious negative outcomes, which requires reflection and rethinking.

Outcome and relapse risks of thrombotic thrombocytopaenic purpura: an Egyptian experience.

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.

Achieving access to haemophilia care in low-income and lower-middle-income countries: expanded Humanitarian Aid Program of the World Federation of Hemophilia after 5 years.

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.

Hepatitis B virus (HBV) infection and recombination between HBV genotypes D and E in asymptomatic blood donors from Khartoum, Sudan.

Sudan is a highly endemic area for hepatitis B virus (HBV), and >5% of blood donors are chronically infected. To examine potential strategies to improve HBV blood safety, 404 replacement donor samples previously screened for HBV surface antigen (HBsAg) were tested for antibody to HBV core (anti-HBc), anti-surface antigen (anti-HBs), and HBV DNA. Of 145 anti-HBc-containing samples (36%) identified, 16 retested were HBsAg positive (11%). Anti-HBs was detected in 43/77 (56%) anti-HBc-reactive samples. Six samples were HBsAg(-)/anti-HBc(+)/anti-HBs(+) and contained HBV DNA, meeting the definition of occult HBV infection (OBI). OBIs had low HBV DNA loads (<10 IU/ml) and were genotype B (n = 1) or genotype D (n = 5). Pre-S/S and/or whole genome sequences were obtained from 47 randomly selected HBsAg-positive donors added to the previous 16. Genotype E was identified in 27 strains (57.5%), genotype D in 19 strains (40.5%), and genotype A2 in 1 strain (2%). Two outlier strains within genotype D ultimately were identified as recombinants of genotypes D and E with identical recombination points, suggesting circulating, infectious, recombinant strains. Anti-HBc screening does not appear to be a sustainable blood safety strategy because of the cost and the negative impact on the Sudanese blood supply, even when reduced by anti-HBs testing. Being at the junction between two main African HBV genotypes, genetic recombination occurred and became part of the molecular epidemiology of HBV in Sudan.

Nucleic acid testing (NAT) in high prevalence-low resource settings.

Blood screening by NAT for major transfusion transmitted viral infections (TTIs) was originally intended to complement serology for detection of infected donations. Reports from developed countries showed limited marginal value to NAT blood screening in improving blood safety. Reports on NAT results from Europe indicated yield of 1:0.6 million donations for HBV, <1:M for HCV and HIV-1-related to low prevalence of TTI. In contrast, prevalence of TTI in resource-limited countries is almost always high. As a result, more incident cases can be expected among first-time blood donors. Most reports of NAT blood donation screening in these countries showed NAT confirmed yield as high as 1/2800 for HBV and 1/3100 blood donations for HCV as reported from Thailand and Egypt, respectively. The issues for low resource countries are mostly the high cost of NAT but also the requirements of staff qualification, adequate facilities, reagent procurement and maintenance of delicate equipment. Alternatives to commercial NAT are the use of combos antigen-antibody for HIV and HCV, anti-HBc for HBV and in-house NAT. Most of these alternatives have been reported but very few comparisons are available. Once yield data is available, models for estimation of feasibility and cost-effectiveness are proposed to help decision-making.