Hemophilia is the best known of the inherited bleeding disorders (BD). This is a rare condition that causes disproportionate bleeding, often into joints and vital organs. Factor replacement, ...injecting recombinant or plasma-based clotting factor products directly into the vein, became commonplace to control the disorder in the 1990s and 2000s. Prophylaxis, or injecting replacement factor every few days into people with hemophilia (PWH), has revolutionized patients' lives. In the last few years, other advances in new therapies have entered this space, such as non-factor replacement therapies and gene therapy. With many more research advances on the horizon, the National Hemophilia Foundation (NHF) initiated a State of the Science Research Summit in 2020. This event was attended by over 880 interested parties to help design an agenda of research priorities for inherited BDs for the next decade, based on community consultations. NHF formed multiple Working Groups (WG), each exploring a theme resulting from the community consultations, and presenting their results at the Summit. Led by 2 hematologists who manage and treat PWH daily, the 21-community member WG1 assigned to hemophilia A and B divided into 7 subgroups to identify and organize research priorities for different topic areas. The outcomes focused on prioritizing patients' needs, technological advances, and research in the areas of greatest potential for PWH and those who care for them. The results are a roadmap for the future execution of a research plan that truly serves the community.
Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.
Working group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for hemophilia A and B into concrete research questions and scored their feasibility, impact, and risk.
WG1 defined 63 top priority research questions concerning arthropathy/pain/bone health, inhibitors, diagnostics, gene therapy, the pediatric to adult transition of care, disparities faced by the community, and cardiovascular disease. This research has the potential to empower PWH to thrive despite lifelong comorbidities and achieve new standards of wellbeing, including psychosocial.
Collaborative research and care delivery will be key to capitalizing on current and horizon treatments and harnessing technical advances to improve diagnostics and testing, to advance health equity for all PWH.
We report 2 patients with coinheritance of the X‐linked bleeding disorders hemophilia A and hemophilia B. We describe the family pedigrees, clinical features, and genotyping. The case report ...addresses the key clinical questions of how to manage patients with both hemophilia A and B and how to counsel families regarding recurrence risk. The patients with coinherited hemophilia A and B require a combination of factor VIII and factor IX replacement to achieve hemostasis. We calculated the estimated genomic meiotic recombination frequency between F8 and F9 to be 38%. The findings in these cases are consistent with this calculation. These findings provide critical information for management of families with coinherited hemophilia A and B.
BACKGROUND
ABO is a blood group system of high clinical significance due to the prevalence of ABO variation that can cause major, potentially life‐threatening, transfusion reactions.
STUDY DESIGN AND ...METHODS
Using multiple large‐scale next‐generation sequence data sets, we demonstrate the application of read‐depth approaches to discover previously unsuspected structural variation (SV) in the ABO gene in individuals of African ancestry.
RESULTS
Our analysis of SV in the ABO gene across 6432 exomes reveals a partial deletion in the ABO gene in 32 individuals of African ancestry that predicts a novel O allele.
CONCLUSION
Our study demonstrates the power that analyses of large‐scale sequencing data, particularly data sets containing underrepresented populations, can provide in identifying novel SVs.
Neuraxial anesthesia, as the standard of care for Cesarean deliveries, is associated with decreased blood loss. However, parturients with inherited bleeding disorders are at increased risk for ...epidural hematomas. A small retrospective study has shown that parturients with known factor deficiencies can safely undergo neuraxial anesthesia once the specific factors are replenished. We present a patient who had a considerably increased risk of peripartum bleeding from an unspecified inherited bleeding disorder and was provided a successful neuraxial anesthetic without complications. We discuss the multidisciplinary approach among the surgeons, anesthesiologists, hematologist, and nursing staff to maximize patient safety and comfort.
Recent surveys of the human genome have highlighted the significance of balancing selection in relation to understanding the evolutionary origins of disease-associated variation. Cis-regulatory ...variation at the blood group-related glycosyltransferase B4galnt2 is associated with a phenotype in mice that closely resembles a common human bleeding disorder, von Willebrand disease. In this study, we have performed a survey of the 5′ flanking region of the B4galnt2 gene in several Mus musculus subspecies and Mus spretus. Our results reveal a clear pattern of trans-species polymorphism and indicate that allele classes conferring alternative tissue-specific expression patterns have been maintained for >2.8 My in the genus Mus. Furthermore, analysis of B4galnt2 expression patterns revealed the presence of an additional functional class of alleles, supporting a role for gastrointestinal phenotypes in the long-term maintenance of expression variation at this gene.
Neuraxial anesthesia, as the standard of care for Cesarean deliveries, is associated with decreased blood loss. However, parturients with inherited bleeding disorders are at increased risk for ...epidural hematomas. A small retrospective study has shown that parturients with known factor deficiencies can safely undergo neuraxial anesthesia once the specific factors are replenished. We present a patient who had a considerably increased risk of peripartum bleeding from an unspecified inherited bleeding disorder and was provided a successful neuraxial anesthetic without complications. We discuss the multidisciplinary approach among the surgeons, anesthesiologists, hematologist, and nursing staff to maximize patient safety and comfort.
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