Hemophilia treatment has changed significantly in recent years, progressively improving patients’ quality of life and offering more promising therapeutic approaches, with the ambitious goal of achieving a “hemophilia-free mind.” Bleeding prevention through regular administration of a hemostatic agent (prophylaxis) represents the gold standard treatment to enable affected individuals to lead an active life, comparable to that of the general population. For replacement therapy, extended half-life FVIII and FIX concentrates have been developed, allowing an extension of the time between intravenous administrations and improving adherence to treatment. These new clotting concentrates allow treatment personalization, making it possible to reduce the number of infusions or increase the protection, maintaining higher circulating levels of FVIII or FIX, based on the characteristics and needs of the individual patient. Advances in understanding of the underlying molecular mechanisms have led to the development of therapeutic strategies to promote or improve hemostasis, through generation of thrombin without the need for FVIII or FIX. This represents a promising therapeutic option for patients with and without inhibitors. The molecules that form the basis of non-replacement therapy have the advantage of being administered subcutaneously, have a long half-life, are suitable for long-term prophylaxis, and provide constant protection. Only the humanized bispecific FVIII mimetic antibody emicizumab is already available in clinical practice. The other molecules are aimed at rebalancing hemostasis, by interacting with different physiological mechanisms of anticoagulation (monoclonal anti-TFPI antibodies and an RNA interference molecule able to decrease antithrombin transcription). Finally, gene therapy, which aims to correct the genetic defect underlying hemophilia, represents one of the most promising frontiers.
KEY WORDS: Hemophilia, arthropathy, prophylaxis, quality of life.
