Prophylactic hemostatic therapy to prevent bleeding-related joint and other organ dysfunction has fundamentally transformed the management of severe hemophilia. Before the widespread adoption of such prophylaxis, individuals with severe hemophilia experienced recurrent spontaneous bleeding beginning in early childhood, leading to progressive hemophilic arthropathy, chronic pain, disability, and reduced life expectancy. Based on extensive clinical trials and real-world evidence, regular prophylaxis with CFCs has been established as the only effective treatment strategy for hemophilia that can modify the bleeding phenotype in a clinically meaningful way.
To standardize terminology across clinical practice and research, the ISTH Scientific and Standardization Committee (SSC) published definitions of prophylaxis in hemophilia in 2014. Prophylaxis was defined as the regular administration of hemostatic therapy intended to prevent bleeding. It was categorized into primary, secondary, and tertiary strategies based on the timing of prophylaxis initiation relative to bleeding events and their complications. They have been widely adopted in clinical studies, registries, and treatment guidelines.
Over the past decade, the therapeutic landscape of hemophilia has evolved substantially with the emergence of non-factor therapies (NFTs) and extended half-life products. These therapies differ in mechanisms of action, pharmacokinetics, and administration, but share the ability to enhance hemostasis and prevent bleeding. An ultra-long half-life FVIII concentrate has further expanded available options. These advances enable much earlier initiation of prophylaxis, reduce treatment burden, and minimize the need for central venous access. While concerns regarding inhibitor development persist with CFC exposure, NFTs do not carry the same direct risk profile. Treatment goals have consequently shifted toward the prevention of all bleeding and further optimization of outcomes.
The objective of this SSC communication is to update the definitions of prophylaxis in hemophilia while maintaining conceptual continuity with the widely adopted 2014 framework.
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