Highlights in thrombosis and bleeding disorders

Prof Dr Cédric Hermans, a haematologist at the Cliniques Universitaires Saint-Luc (Brussels, Belgium) presented notable updates regarding thrombosis and bleeding disorders.

Most patients with deep venous thrombosis or pulmonary embolism receive short-term treatment. However, some individuals require extended anticoagulation therapy. Current evidence supports the use of direct oral anticoagulants (DOACs) for these patients. Clinicians can choose between high-dose and reduced-dose regimens, but randomised data comparing these options have been lacking. Data from a late-breaking abstract addressed this issue. The study compared outcomes for patients receiving low-dose versus high-dose DOACs over an extended period. Results showed that the low-dose regimen was non-inferior to the high-dose regimen in preventing thrombotic events. Importantly, the lower dose also resulted in fewer bleeding complications, making it a safer option. This evidence supports a shift toward greater use of reduced-dose DOACs in clinical practice. Moreover, the study found no additional benefit of high-dose therapy in specific groups, such as patients with obesity or severe PE. These findings reassure clinicians about the efficacy and safety of lower-dose anticoagulation in long-term therapy.

A promising development in anticoagulation reversal was presented by researchers from the Netherlands. They have bioengineered a new factor X that retains full activity but is not inhibited by DOACs. This innovation could rapidly restore coagulation in patients with acute bleeding or requiring urgent reversal of DOAC effects. The agent has shown efficacy in animal models and promising results in healthy individuals. Further validation through a large clinical trial is now necessary.

Gene therapy for haemophilia has become feasible in 2024, though it is not yet widely adopted. Several challenges remain, including high costs and technical complexity. Current gene therapy approaches aim to restore the production of factor VIII in the liver, which has inherent limitations. Researchers from India proposed an innovative alternative using autologous bone marrow transplantation. This method involves harvesting hematopoietic stem cells from patients, modifying CD4 cells with a viral vector to produce factor VIII, and reinfusing the altered cells after conditioning. In a study involving five patients, three demonstrated significant improvement with this approach. The findings were simultaneously published in the New England Journal of Medicine, emphasizing the potential of this technique as a breakthrough in haemophilia treatment. 

Recent data also highlighted advancements in classical gene therapy for haemophilia, particularly the liver-targeted approach using AAV vectors. The AFFINE study involving 75 patients treated with the AAV6 serotype showed promising results, however, long-term outcomes remain uncertain, as patients may experience reduced factor VIII production over time. Further observation is needed to determine the durability of these effects.

For haemophilia B, researchers are exploring the use of patient-derived B lymphocytes, which are modified to produce factor IX and re-injected. Another focus is gene editing, which holds the potential for long-lasting solutions. Beyond gene therapy, alternative treatments continue to advance. Bispecific antibodies that mimic factor VIII and agents that rebalance coagulation were discussed. These therapies significantly reduce bleeding episodes and improve patient’s quality of life by easing the treatment burden. While not groundbreaking, the updates confirm their efficacy and meaningful impact on managing haemophilia. 

Newborns diagnosed with haemophilia can benefit from early treatment with agents like emicizumab, which can be initiated shortly after birth. Recent data confirm the safety and efficacy of these therapies, and I strongly encourage colleagues to adopt their use promptly in young patients.

New data were also presented in the field of hereditary haemorrhagic telangiectasia, a challenging condition to manage. However, promising developments include new agents, particularly an oral treatment that may significantly reduce the frequency and severity of nosebleeds in these patients. Although these therapies are still in the early stages, they offer hope for improved management of this condition.