Hemophilia is a rare congenital bleeding disorder that results from
complete or partial deficiency of blood coagulation factor (F)VIII (hemophilia A) or FIX
(hemophilia B) due to pathogenic variants in their coding genes. Hemophilia requires
complex management. To date, there is no evidence-based clinical practice guideline on
hemophilia treatment based on the Grading of Recommendations Assessment, Development,
and Evaluation (GRADE) approach.
This evidence-based clinical practice guideline from the International Society
on Thrombosis and Haemostasis aims to provide an overview of evidence and
support patients, caregivers, hematologists, pediatricians, other clinicians, researchers,
and stakeholders in treatment decisions about congenital hemophilia A and B.
The International Society on Thrombosis and Haemostasis formed a multidisciplinary
guideline panel of physicians and patients with global representation,
balanced to minimize potential bias from conflicts of interest. The panel prioritized a set
of clinical questions and outcomes according to their importance for clinicians and
patients. A methodological team supported the guideline development process,
including searching for evidence and performing systematic reviews. The GRADE
approach was used, including GRADE Evidence to Decision frameworks. The recommendations
were subject to public comment.
The panel selected 13 questions, of which 11 addressed the treatment of
hemophilia A and 2 the treatment of hemophilia B. Specifically, the panel addressed
questions on prophylactic and episodic treatment with FVIII concentrates, bypassing
agents, and nonfactor therapy (emicizumab) for hemophilia A (with and without inhibitors)
as well as immune tolerance induction for hemophilia A. For hemophilia B, the
panel addressed questions on prophylactic and episodic treatment of bleeding events
with FIX concentrates. Agreement was reached for all 13 recommendations, of which 7
(54%) were based on evidence from randomized clinical trials, 3 (23%) on observational
studies, and 3 (23%) on indirect comparisons.
Conclusion: Strong recommendations were issued for prophylactic over episodic
treatment for severe and moderately severe hemophilia A and B. Only conditional
recommendations were issued for the remaining questions. Future research should
focus on direct treatment comparisons and the treatment of hemophilia B with and
without inhibitors. Future updates of this guideline will provide an updated evidence
synthesis on the current questions and focus on new FVIII and FIX concentrates, novel
nonfactor therapies, and gene therapy for severe and nonsevere hemophilia A and B.
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Site / Data. J Thromb Haemost 2024 Sep;22(9):2629-2652.
Title Linee guida per la pratica clinica della Società Internazionale sulla Trombosi e l’Emostasi per il trattamento dell’emofilia congenita A e B basate sulla metodologia di valutazione, sviluppo e valutazione della classificazione delle raccomandazioni
Authors Suely M. Rezende et al.