Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research to advance the health of people with inherited bleeding disorders with the potential to menstruate.

BACKGROUND: People who have or had the potential to menstruate (PPM) with inherited bleeding disorders (BD) face particular challenges receiving appropriate diagnosis and care and participating in research. As part of an initiative to create a National Research Blueprint for future decades of research, the National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive all-stakeholder consultations to identify the priorities of PPM with inherited BDs and those who care for them. RESEARCH DESIGN AND METHODS: Working group (WG) 4 of the NHF State of the Science Research Summit distilled community-identified priorities for PPM with inherited BDs into concrete research questions and scored their feasibility, impact, and risk. RESULTS: WG4 identified important gaps in the foundational knowledge upon which to base optimal diagnosis and care for PPM with inherited BDs. They defined 44 top-priority research questions concerning lifespan sex biology, pregnancy and the post-partum context, uterine physiology and bleeding, bone and joint health, health care delivery, and patient-reported outcomes and quality-of-life. CONCLUSIONS: The needs of PPM will best be advanced with research designed across the spectrum of sex and gender biology, with methodologies and outcome measures tailored to this population, involving them throughout.

Up to 1% of cisgender women and girls have an inherited bleeding disorder (BD). Common symptoms include heavy menstrual bleeding (HMB), heavy bleeding after giving birth known as post-partum hemorrhage (PPH), nose bleeds, bleeding from the mouth, and excessive bleeding after surgery or procedures. They can also experience bleeding into their muscles, joints, and even into the brain. Uterine bleeding, such as from HMB and PPH, can impact the lives of anyone who has or had a uterus, a group we designate as people who have or had the potential to menstruate (PPM).Many PPM with an inherited BD do not receive diagnosis, treatment, and care needed due to a lack of expertise among health care professionals and the public, misunderstanding, and bias. Uncertainty about "normal" versus "abnormal" bleeding can contribute to a lack of diagnosis, treatment, and care. Language, such as the label of "carrier," can be a barrier to accessing treatment and care for PPM.People with inherited BDs, health care professionals with various expertise and focus, and researchers worked together to identify the research that would most improve the lives of PPM, in six focus areas where there are major gaps in knowledge and the lack of standards required for accurate diagnosis.

An Altered Treatment Plan Based on Direct to Consumer (DTC) Genetic Testing: Personalized Medicine from the Patient/Pin-cushion Perspective.

Direct to consumer (DTC) genomic services facilitate the personalized and participatory aspects of "P4" medicine, but raise questions regarding use of genomic data in providing predictive and preventive healthcare. We illustrate the issues involved by describing a pregnancy management case in which a treatment plan was modified based on a DTC result. A woman whose personal and family history were otherwise unremarkable for thromboembolism learned through DTC testing about the presence of a prothrombin (factor 2) gene mutation (rs1799963). Twice daily injections of enoxaparin were recommended throughout pregnancy for this patient who, without prior knowledge of this mutation, would not have been offered such therapy. Moreover, genetically based medical guidelines are a moving target, and treatment of thrombophilic conditions in asymptomatic patients is controversial. We address the state of the art in actionable personalized medicine with respect to clotting disorders in pregnancy, as well as other factors at play- economics, patient preference, and clinical decision support. We also discuss what steps are needed to increase the utility of genomic data in personalized medicine by collecting information and converting it into actionable knowledge.

Thrombophilia screening in asymptomatic children.

Children with a family history of thrombophilia and/or thrombosis are often referred to pediatric thrombosis centers for evaluation. This article reviews the risks and benefits of thrombophilia testing in this unique population. The article also reviews an approach to testing including a step-wise evaluation and involvement of a genetic counselor.