A new hemophilia carrier nomenclature to define hemophilia in women and girls: Communication from the SSC of the ISTH

Karin P M van Galen, Roseline d'Oiron, Paula James, Rezan Abdul-Kadir, Peter A Kouides, Roshni Kulkarni, Johnny N Mahlangu, Maha Othman, Flora Peyvandi, Dawn Rotellini, Rochelle Winikoff, Robert F Sidonio, Karin P M van Galen, Roseline d'Oiron, Paula James, Rezan Abdul-Kadir, Peter A Kouides, Roshni Kulkarni, Johnny N Mahlangu, Maha Othman, Flora Peyvandi, Dawn Rotellini, Rochelle Winikoff, Robert F Sidonio

Abstract

Hemophilia A and B predominantly attracts clinical attention in males due to X-linked inheritance, introducing a bias toward female carriers to be asymptomatic. This common misconception is contradicted by an increasing body of evidence with consistent reporting on an increased bleeding tendency in hemophilia carriers (HCs), including those with normal factor VIII/IX (FVIII/IX) levels. The term HC can hamper diagnosis, clinical care, and research. Therefore, a new nomenclature has been defined based on an open iterative process involving hemophilia experts, patients, and the International Society on Thrombosis and Haemostasis (ISTH) community. The resulting nomenclature accounts for personal bleeding history and baseline plasma FVIII/IX level. It distinguishes five clinically relevant HC categories: women/girls with mild, moderate, or severe hemophilia (FVIII/IX >0.05 and <0.40 IU/ml, 0.01-0.05 IU/ml, and <0.01 IU/ml, respectively), symptomatic and asymptomatic HC (FVIII/IX ≥0.40 IU/ml with and without a bleeding phenotype, respectively). This new nomenclature is aimed at improving diagnosis and management and applying uniform terminologies for clinical research.

Keywords: bleeding; hemophilia; phenotype; women’s health.

Conflict of interest statement

Dr. van Galen has received research support from CSL Behring, Bayer, and Octapharma and speakers’ fees from Takeda, CSL Behring, and Bayer. Dr. d’Oiron has served as a consultant for Baxalta/Shire, Bayer, CSL Behring, LFB, NovoNordisk, Octapharma, Pfizer, Roche, and Sobi, Spark and was invited speaker for Baxalta/Shire, Bayer, CSL Behring, LFB, NovoNordisk, Octapharma, Pfizer, Roche, and Sobi, Spark. Dr. Sidonio has participated in advisory boards for Novo Nordisk, Sanofi, Genentech, Octapharma, Takeda, Bayer, Sigilon, Catalyst, Biomarin, and Pfizer. Dr. James has received research funding from Bayer. Dr. Mahlangu received research grants from BioMarin, Catalyst Biosciences, CSL, Freeline Therapeutics, Novo Nordisk, Novartis, Pfizer, Sanofi, Roche, Spark, Takeda, and was an advisory board/consultant for CSL Behring, Catalyst Biosciences, Freeline Therapeutics, Novo Nordisk, Roche, Sanofi, Spark, Takeda. Dr. Kulkarni has served on the advisory boards of Sanofi‐Genzyme, NovoNordisk, Genentech, CSL Behring, Octapharma, Pfizer, Shire/Takeda, Catalyst Bioscience, and Bayer. Prof Peyvandi has received speaker fees for participating in educational symposia and advisory boards for Roche, Sanofi, Sobi, and Takeda. D. Rotellini has served on advisory boards for Bayer, BioMarin, and Pfizer with National Hemophilia Foundation receiving all honorarium. Prof Abdul‐Kadir received lecture fees/educational grants from Pfizer, NovoNordisk, Takeda, and ViforParma. Dr. Sidonio has IIS funded by Takeda, Genentech, and Octapharma and is the PI for the Wil‐29/Wil‐31 studies (Octapharma) and BAX‐855 study and has served as a consultant for Bayer, Sigilon, Roche/Genentech, Octapharma, Grifols, Biomain, Sanofi, and Novo Nordisk. None of the other authors has any conflict of interest to declare.

© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

Figures

FIGURE 1
FIGURE 1
New nomenclature for hemophilia carriers and women and girls with hemophilia. The term “asymptomatic hemophilia carrier” solely reflects the bleeding phenotype, not the actual burden of being a hemophilia carrier. FVIII/FIX, factor VIII/IX; IU/ml, international units per milliliter

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