The 66th ASH Annual Meeting and Exposition took place from December 7-10, 2024, in San Diego, California, as well as online. This event is the premier hematology gathering of the year, attracting over 30,000 health professionals, clinicians, researchers, educators, and other industry experts. Attendees can expect a multitude of sessions, thousands of abstracts, and numerous opportunities to engage with the latest advancements in hematology.

At ASH 2024, several significant abstracts were presented focusing on bleeding & clotting disorders. These abstracts delved into topics such as hereditary hemorrhagic telangiectasia (HHT), Von Willebrand disease, and acquired hemophilia A, among others. The following presentations, which are highlighted below, shed light on important developments in the management of bleeding & clotting disorders and demonstrate the ongoing efforts to enhance patient outcomes.

Use of Low Dose Tranexamic Acid in Patients with Bleeding Disorders

  • Tranexamic acid (TXA) is a potent antifibrinolytic medication that works by inhibiting fibrinolysis through the displacement of plasminogen from fibrin. This drug is commonly utilized to manage bleeding in patients with trauma, heavy menstrual bleeding, postpartum hemorrhage, and individuals undergoing procedures or surgeries with bleeding disorders. Despite its widespread use, the lack of comprehensive dose exposure and pharmacokinetic studies has resulted in varying dosing protocols in different clinical trials.
  • This study presents compelling evidence supporting the safety and efficacy of low-dose oral TXA at 650 mg thrice daily in preventing heavy menstrual bleeding (HMB) and bleeding associated with minor procedures or surgeries in patients with bleeding disorders
  • Summary

Novel Variants in Persons with Rare Coagulation Disorders across Hemophilia Treatment Centers in the United States

  • The prevalence of ultra-rare bleeding coagulation disorders remains largely unknown, yet it is crucial to comprehend the necessity for specialized healthcare services and the connection of individuals to appropriate treatment. Identifying and characterizing these disorders can be challenging due to the lack of specialized testing and the presence of multiple conditions that can impact bleeding patterns. To gain a better understanding of the nature and frequency of ultra-rare bleeding coagulation disorders in the United States, the American Thrombosis and Hemostasis Network (ATHN) launched ATHN 10. This collaborative initiative involves 140 ATHN-affiliated hemophilia treatment centers (HTCs) working together to conduct whole gene sequencing and gather detailed phenotypic data, including bleeding scores, from patients diagnosed with one of the 31 identified ultra-rare bleeding coagulation disorders.
  • By utilizing the resources available at ATHN-affiliated HTCs and the laboratory services at the Center for Inherited Disorders (CIBD)/Hematology Advanced Diagnostic Laboratory (CAP/CLIA Certified), the ATHN 10 project has successfully overcome barriers associated with genetic testing. This has led to an increased understanding of the incidence of new pathogenic variants at a reduced cost, enabling HTCs to offer more tailored care and genetic counseling. Furthermore, whole gene sequencing has confirmed the significance of specific genetic hot spots in clotting factor genes, as well as the impact of splice site variants on factor activity levels and bleeding patterns. This advancement in knowledge is crucial for improving the diagnosis and treatment of individuals with ultra-rare bleeding coagulation disorders.
  • Summary

A Randomized, Placebo-Controlled, Multicenter Proof-of-Concept (POC) Study to Assess the Safety and Efficacy of the Novel Allosteric AKT Inhibitor, VAD044, in Adults with Hereditary Hemorrhagic Telangiectasia (HHT)

  • Hereditary hemorrhagic telangiectasia (HHT) is the second most common inherited bleeding disorder, affecting 1 in 5000 people. Despite its prevalence, there are currently no approved therapies for HHT. This condition leads to severe recurrent nosebleeds, chronic gastrointestinal bleeding, and complications in the vascular system that result in significant clinical and psychosocial challenges, ultimately reducing life expectancy.
  • In individuals with HHT, mutations in endoglin or ALK1 cause an overactivation of the serine/threonine kinase, AKT, which leads to the formation of telangiectasia and arteriovenous malformations in visceral organs. VAD044 is an oral, once-daily allosteric selective inhibitor of AKT1/2 that is being developed as a potential disease-modifying therapy for HHT.
  • The primary results from a proof-of-concept study (NCT05406362) of VAD044 in adults with HHT have shown promising outcomes. The safety and tolerability of oral VAD044 for 12 weeks were found to be similar to placebo, with mostly mild drug class effects that resolved while on the study drug.
  • Compared to placebo, VAD044 at a dose of 40 mg demonstrated significant improvements in epistaxis parameters, disease activity measures, and a dose-dependent enhancement in Patient Global Impression of Change. These findings support the continued development of VAD044 as the first novel therapy specifically designed for HHT, addressing the significant unmet needs of patients with this condition. An open-label extension trial is currently underway to further investigate the potential of VAD044.
  • Summary

Disparities in Real-World Treatment Patterns Among Patients with Von Willebrand Disease in a Large US Population-Based Dataset

  • Von Willebrand disease (VWD) is a prevalent inherited bleeding disorder, impacting approximately 1% of the population. The diverse range of bleeding symptoms experienced by individuals with VWD, coupled with the absence of a clear consensus on treatment approaches, has led to variability in the care provided. Our study utilized the largest US administrative database to analyze national trends in bleeding events and treatments for patients with VWD. The primary objective of this research was to provide a comprehensive overview of patient characteristics, bleeding incidents, and treatment strategies for individuals with VWD using a vast national claims database. By leveraging National Drug Codes (NDCs) within this database, we were able to conduct a detailed analysis of treatment patterns and disease burden within the VWD population over time.
  • The findings revealed a wide range of bleeding phenotypes and hemostatic medications utilized in the treatment of VWD patients. Despite the availability of prophylactic treatments, only a minority of individuals with VWD and bleeding comorbidities received such care, even when experiencing severe and frequent bleeds. The burden of treatment was evident, with VWF replacements often requiring 2 to 3 infusions per week for prophylaxis. Among VWD patients with bleeding comorbidities, heavy menstrual bleeding and nosebleeds were the most prevalent bleeding phenotypes, although they may be underrepresented in claims data. Notably, only a small percentage of patients received VWF replacement therapies, highlighting potential gaps in treatment provision for individuals with VWD.
  • Summary

Physician-Assessed Vs. Patient-Reported Bleeding Scores in an Undiagnosed Clinic Population

  • The International Society of Thrombosis and Haemostasis (ISTH) has recommended that a healthcare provider administer a bleeding assessment tool (ISTH-BAT) to evaluate bleeding symptoms. The scores from the ISTH-BAT can then help guide further testing or referral to a specialist. However, the ISTH-BAT is time-consuming to administer and requires a trained assessor to interpret and categorize patient responses. A patient-completed version of the tool (Self-BAT) has been developed and tested in von Willebrand Disease, but has not been compared to the ISTH-BAT in undifferentiated patients during a clinic visit. The objective of this study was to compare the results of the ISTH-BAT and Self-BAT in adult patients seeking evaluation for a potential bleeding disorder in a hematology clinic.
  • Moderate overall reliability was observed between the ISTH-BAT and Self-BAT. Self-BAT scores were generally higher than ISTH-BAT scores and showed slightly increased sensitivity in diagnosing bleeding disorders using established cut-off values. However, assessing bleeding severity in certain areas may be more subjective or unfamiliar to patients, leading to discrepancies. Further research is needed to determine the best way to incorporate patient self-reports with clinician assessments in evaluating bleeding disorders.
  • Summary

Medical and Surgical Management for Heavy Menstrual Bleeding in Women with Ehlers-Danlos Syndrome

  • Ehlers-Danlos syndrome (EDS) encompasses a diverse group of inherited collagen disorders that are often associated with bleeding tendencies. While easy bruising is a common feature in many subtypes of EDS, it is not considered a formal diagnostic criterion in the most prevalent subtype, hypermobile EDS (hEDS). Consequently, the diagnosis of EDS may be delayed in individuals experiencing unexplained bleeding issues. Research indicates that heavy menstrual bleeding (HMB) affects a significant proportion of individuals with EDS, with limited data available on effective management strategies. Previous studies have predominantly focused on the use of hormonal therapies in pediatric and adolescent populations. The aim of this study is to investigate the prevalence of gynecological bleeding and assess the medical and surgical management of HMB in women with EDS, in comparison to age-matched individuals with von Willebrand disease (VWD).
  • Our findings reveal that women with EDS and bleeding tendencies often face delays in diagnosis, despite a high prevalence of family history and gynecological bleeding. Gynecology consultations, hormonal therapies, and the use of tranexamic acid (TXA) for HMB all present opportunities for improvement. The delayed diagnosis and suboptimal medical interventions may contribute to higher rates of surgical interventions for HMB in individuals with EDS compared to those with VWD of similar age.
  • Summary

Clinical and Economic Outcome Analysis of First-Line Immunosuppression in Acquired Hemophilia A

  • Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by inhibitory antibodies that neutralize factor VIII (FVIII) activity, resulting in significant morbidity and mortality due to bleeding and complications of immunosuppressive treatment (IST). Individuals with AHA are particularly susceptible to the adverse effects of IST, as they are often older and have multiple comorbidities. While rituximab may offer a less toxic alternative to traditional IST like cyclophosphamide, it is costly and not always readily available. Both rituximab and cyclophosphamide are recommended as first-line treatment options for high-risk patients with AHA, as outlined in the current international treatment guidelines (Tiede, Haematologica, 2020).
  • This study aimed to compare the efficacy, safety, and economic impact of first-line IST regimens in Canadian patients with AHA. In this Canadian cohort, all IST regimens demonstrated similar overall survival rates and rates of complete remission. However, patients treated with steroids and rituximab (B) experienced the lowest rates of relapse, as well as a lower incidence of infections and grade 3/4 adverse events compared to regimens containing cyclophosphamide. This study is the first of its kind to comprehensively evaluate the economic burden of AHA treatment, revealing that the majority of costs stem from hemostatic treatments rather than IST. Variations in costs between regimens may be attributed to the proportion of high-risk patients and the frequency and severity of bleeding events.
  • Summary

Thank you for joining us for this recap of ASH Annual Meeting. We recommend visiting this link to explore all the posters presented at the event. We look forward to seeing you at ASH 2025!

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