Recent strides in hemophilia therapies and enhanced imaging technology have transformed patient care, offering hope to those with this historically debilitating disorder. Annette von Drygalski, MD, PharmD, RMSK, from the University of California San Diego, discussed these advancements during a session at the 2024 ASH Annual Meeting.

“Over the past decade, remarkable scientific advancements have significantly improved hemophilia care,” stated von Drygalski. Compared to the 1960s when hemophilia was often fatal during childhood, today’s patients can expect normal lifespans thanks to innovative prophylactic treatments, including novel clotting factor molecules, factor-less therapies, and pioneering gene therapies.

Understanding Hemophilia: A Quick Overview

Hemophilia affects approximately 25 cases per 100,000 males for hemophilia A and 5 per 100,000 for hemophilia B. This condition is characterized by a deficiency of clotting factors, specifically factor VIII in hemophilia A and factor IX in hemophilia B. The deficiency can lead to spontaneous bleeding in joints and muscles, particularly in childhood, and if untreated, can result in significant musculoskeletal damage.

Severity of hemophilia is classified based on the level of clotting factor activity in the blood. Severe forms, defined as less than 1% of normal clotting factor activity, predispose patients to spontaneous joint and muscle bleeds.

Innovations in Treatment

Historically, treating hemophilia required frequent intravenous infusions of clotting factors to maintain levels that would prevent spontaneous bleeding. However, this ‘sawtooth’ pattern of fluctuating factor levels often left patients vulnerable during low points.

The introduction of extended half-life clotting factors is revolutionizing care by stabilizing factor levels and reducing the frequency of infusions. “The fundamentals of prophylaxis remain, but now include innovative rebalancing agents and gene therapies,” noted von Drygalski.

Rebalancing agents, such as Marstacimab (Hympavzi) and Emicizumab (Hemlibra), act by mimicking the missing clotting factors, minimizing the risk of bleeding. Moreover, groundbreaking gene therapies like etranacogene dezaparvovec (Hemgenix) for hemophilia B and valoctocogene roxaparvovec (Roctavian) for hemophilia A present long-term solutions by restoring normal clotting factor production with a single infusion.

Hemophilic Arthropathy: A Continuing Battle

Despite these advancements, hemophilic arthropathy—a concerning result of recurrent joint bleeds—remains a significant issue. This condition leads to severe joint damage and functional impairment over time, even with improved prophylactic measures. Iron deposition in the joint space, caused by the breakdown of red blood cells during bleeds, is identified as a key factor in joint deterioration.

“It’s crucial to prevent joint bleeding, or we risk progression of complications," said von Drygalski, pointing to the need for a deeper understanding of the disease's pathology and improved imaging tools for timely and effective management.

Enhancements in Imaging Techniques

Traditional imaging methods, like X-rays and MRIs, often miss early joint changes and can be costly. Point-of-care musculoskeletal ultrasound has emerged as a critical tool in identifying joint bleeds and monitoring overall joint health. “Ultrasound allows for clear differentiation between joint fluid and synovium,” explained von Drygalski.

To further improve patient care, the Joint Activity and Damage Exam (JADE) protocol utilizes ultrasound to provide an in-depth assessment of joint conditions by measuring cartilage thickness, soft tissue expansion, and osteochondral changes. This streamlined approach could eventually enable patients to conduct self-imaging, enhanced by artificial intelligence for smart assessments.

The Road Ahead

As hemophilia treatment options continue to evolve, the healthcare community remains focused on overcoming remaining challenges, particularly in joint health management. Innovative therapeutics and advanced imaging techniques promise to usher in a new era of care for hemophilia patients—an era where life expectancy is no longer a concern and quality of life is a priority. The journey to complete care may still be ongoing, but the future appears hopeful.