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CC BY-NC-ND 4.0 · TH Open 2022; 06(04): e365-e377
DOI: 10.1055/s-0042-1757745
Review Article

The Limitations and Unmet Needs of the Five Cornerstones to Guarantee Lifelong Optimization of Prophylaxis in Hemophilia Patients

Ramiro Núñez   †*
1   Hemophilia Unit, Hospital Universitario Virgen del Rocío, Sevilla, Andalucía, Spain
,
María Teresa Álvarez-Román   †*
2   Department of Hematology and Hemotherapy, La Paz University Hospital-IdiPaz, Madrid, Spain
,
Santiago Bonanad 
3   Haemostasis and Thrombosis Unit, Hospital Universitari i Politècnic La Fe, València, Spain
,
José Ramón González-Porras 
4   Hematology Department, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (Ibsal), Salamanca, Spain
,
Hortensia De La Corte-Rodriguez
5   Department of Physical and Rehabilitation Medicine, La Paz University Hospital-IdiPaz, Madrid, Spain
,
Rubén Berrueco
6   Pediatric Hematology Department, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, Barcelona, Spain
7   Institut de Recerca, Pediàtrica Hospital Sant Joan de Déu de Barcelona (IRP-HSJD0), Barcelona, Spain
8   Instituto Nacional de Investigación Biomédica en Enfermedades Raras (CIBER ER), Instituto de Salud Carlos III, Madrid, Spain
,
Víctor Jiménez-Yuste
2   Department of Hematology and Hemotherapy, La Paz University Hospital-IdiPaz, Madrid, Spain
› Author Affiliations Funding This study was funded by Novo Nordisk.
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Abstract

Prophylaxis to prevent bleeding is highly recommended for hemophilia patients. The development of new drugs and tools for modeling personalized prophylaxis provides the means for people with hemophilia to lead active lives with a quality of life comparable to that of nonhemophilic individuals. The choice of regimens must be made on a highly individual basis. Unfortunately, reference guides neither always concur in their recommendations nor provide directions to cover all possible scenarios. In this review, a group of experts identify the significant limitations and unmet needs of prophylaxis, taking advantage of their clinical experience in the disease, and supported by a rigorous literature update. To perform a more systematic and comprehensive search for gaps, the main cornerstones that influence decisions regarding prophylactic patterns were first identified.

Bleeding phenotype, joint status, physical activity, pharmacokinetics/medication properties, and adherence to treatment were considered as the primary mainstays that should allow physicians guiding prophylaxis to secure the best outcomes. Several challenges identified within each of these topics require urgent attention and agreement. The scores to assess severity of bleeding are not reliable, and lead to no consensus definition of severe bleeding phenotype. The joint status is to be redefined in light of new, more efficient treatments with an agreement to establish one scale as the unique reference for joint health. Further discussion is needed to establish the appropriateness of high-intensity physical activities according to patient profiles, especially because sustaining trough factor levels within the safe range is not always warranted for long periods. Importantly, many physicians do not benefit from the advantages provided by the programs based on population pharmacokinetic models to guide individualized prophylaxis through more efficient and cost-saving strategies. Finally, ensuring correct adherence to long-term treatments may be time-consuming for practitioners, who often have to encourage patients and review complex questionnaires.

In summary, we identify five cornerstones that influence prophylaxis and discuss the main conflicting concerns that challenge the proper long-term management of hemophilia. A consensus exercise is warranted to provide reliable guidelines and maximize benefit from recently developed tools that should notably improve patients' quality of life.

Keywords

hemophilia - prophylaxis - bleeding phenotype - joint status - physical activity - pharmacokinetics - treatment adherence

Authors' Contributions

R.N., M.T.A., S.B., J.R.G.P., H.C.R., R.B., and V.J.Y. designed this article, researched the literature, prepared the contents of all sections in the paper, and co-wrote and reviewed this collaborative research paper.


Disclosures

The authors disclose financial activities outside the submitted work. R.N. has received reimbursement for attending symposia/congresses and/or honoraria for speaking and/or honoraria for consulting and/or funds for research from Takeda, Bayer, CSL-Behring, Grifols, Novo Nordisk, Sobi, Roche, Octapharma, Sanofi, and Pfizer. M.T.A. has received reimbursement for attending symposia/congresses and/or honoraria for speaking and/or honoraria for consulting, and/or funds for research from Takeda, Bayer, CSL-Behring, Grifols, Novo Nordisk, Sobi, Roche, Octapharma, Biomarin, Sanofi, Pfizer, Novartis, and Amgen. S.B. has received reimbursement for attending symposia/congresses and/or honoraria for speaking and/or honoraria for consulting and/or funds for research from Takeda, Bayer, CSL-Behring, Grifols, Novo Nordisk, Sobi, Roche, Octapharma, Biomarin, Sanofi, and Pfizer. J.R.G.P. has received fees for consulting services by Amgen, Novartis, SOBI, Grifols, and CSL Behring and speaking honoraria from Novo Nordisk, Shire, SOBI, Roche, Daiichi Sankyo, Pfizer, Rovi, Amgen, and Novartis. H.C.R. has received reimbursement for attending symposia/congresses and/or honoraria for speaking and/or consulting and/or funds for research from Pfizer, Roche, Sobi, NovoNordisk, Takeda, and Bayer. R.B. has received reimbursement for attending symposia/congresses and/or honoraria for speaking and/or honoraria for consulting and/or funds for research from Takeda, Bayer, CSL-Behring, Novo Nordisk, Sobi, Roche, Boehringer-Ingelheim, and Pfizer. V.J.Y. has received reimbursement for attending symposia/congresses and/or honoraria for speaking and/or honoraria for consulting and/or funds for research from Takeda, Bayer, CSL-Behring, Grifols, Novo Nordisk, Sobi, Roche, Octapharma, Biomarin, Sanofi, and Pfizer. The preparatory meetings have been financed by Novo Nordisk.


†* These two authors contributed equally to the work.




Publication History

Received: 22 February 2022

Accepted: 25 July 2022

Article published online:
11 November 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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