Original Articles
Vol. 4 No. 3 (2025)
The landscape of rare coagulation factor deficiency management in Italy: a national hemophilia center survey
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 5 November 2025
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Background: Rare bleeding disorders (RBDs) are a group of inherited conditions caused by deficiencies in specific coagulation factors, excluding hemophilia A/B and von Willebrand disease. Individually rare, they pose a significant challenge for diagnosis and management due to diverse clinical presentations and low awareness. This study aimed to provide an overview of RBDs.
Methods: An online survey was sent to Italian hemophilia treatment centers.
Results: Nineteen centers responded. The diagnostic approach was tiring, but key definitions showed significant variability. This included defect severity, target hemostatic levels for surgery, eligibility thresholds for rare disease exemptions. The use of prophylaxis varied, although favored in severe FII, FVII, FX, and FXIII defects. Treatment primarily involved factor-specific concentrates and tranexamic acid. While inhibitor development was considered uncommon, it was a recognized risk. Bleeding management during dental procedures, pregnancy, and delivery also showed variability. Additionally, normal factor levels in neonates differed across centers.
Conclusions: This study highlights a good consensus for managing certain RBDs (FII, FVII, FX, FXIII) in Italy. However, significant heterogeneity persists, emphasizing the need for greater standardization and further research in several key areas.
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Citations
1. Peyvandi F, Duga S, Akhavan S, Mannucci PM. Rare coagulation deficiencies. Haemophilia 2002;8:308-21. DOI: https://doi.org/10.1046/j.1365-2516.2002.00633.x
2. Peyvandi F, Mannucci PM. Rare coagulation disorders. Thromb Haemost 1999;82:1207-14. DOI: https://doi.org/10.1055/s-0037-1614361
3. Casini A, Al-Samkari H, Hayward C, Peyvandi F. Rare bleeding disorders: Advances in management. Haemophilia 2024:30;60-9. DOI: https://doi.org/10.1111/hae.14986
4. Peyvandi F, Palla R, Menegatti M, Siboni SM, et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 2012;10:615-21. DOI: https://doi.org/10.1111/j.1538-7836.2012.04653.x
5. Peyvandi F, Di Michele D, Bolton-Maggs PH, et al. Classification of rare bleeding disorders (RBDs) based on the association between coagulant factor activity and clinical bleeding severity. J Thromb Haemost 2012;10:1938-43. DOI: https://doi.org/10.1111/j.1538-7836.2012.04844.x
6. Mumford AD, Ackroyd S, Alikhan R, et al. Guideline for the diagnosis and management of the rare coagulation disorders: a United Kingdom Haemophilia Centre Doctors' Organization guideline on behalf of the British Committee for Standards in Haematology. Br J Haematol 2014;167:304-26. DOI: https://doi.org/10.1111/bjh.13058
7. Mohsenian S, Seidizadeh O, Cairo A, et al. The genetic spectrum of rare bleeding disorders. J Thromb Haemost 2025;23:2763-75. DOI: https://doi.org/10.1016/j.jtha.2025.06.005
8. Mariani G, Lo Coco L, Bernardi F, Pinotti M. Molecular and clinical aspects of factor VII deficiency. Bood Coagul Fibrinolysis 1998;9:S83-8.
9. Kohler HP, Ichinose A, Takamatsu J, Saito H. Molecular analysis of factor XIII deficiency: characterization of a novel mutation in a patient with severe bleeding diathesis. Blood 1991;78:1320-26.
10. Palla R, Peyvandi F, Shapiro AD. Rare bleeding disorders: diagnosis and treatment. Blood 2015;125:2052-61. DOI: https://doi.org/10.1182/blood-2014-08-532820
11. Benítez Hidalgo O, Martinez Garcia MF, et al. VHrare Study: Prevalence, clinical features, and management of severe rare bleeding disorders in a large cohort. EJHaem 2023 4:476-82. DOI: https://doi.org/10.1002/jha2.664
12. Shapiro AD, Soucie JM, Peyvandi F, et al. Knowledge and therapeutic gaps: a public health problem in the rare coagulation disorders population. Am J Prev Med 2011;41:S324-31. DOI: https://doi.org/10.1016/j.amepre.2011.09.021
13. Stern DH, Nossel HL, Owen J. Acquired antibody for factor XI in a patient with congenital Factor XI deficiency. J Clin Invest 1982;69:1270-6. DOI: https://doi.org/10.1172/JCI110566
14. Karaman S, Akkaya E, Genc S, et al. Congenital factor XIII deficiency with the presence of inhibitor: a case study. J Pediatr Hematol Oncol 2021;43:e99-e102. DOI: https://doi.org/10.1097/MPH.0000000000001671
15. Ramazanpour N, Zaker F, Biswas A, Dorgalaleh A. Inhibitor in congenital factor VII deficiency; a rare but serious therapeutic challenge. A systematic literature review. J Clin Med 2021;10:211. DOI: https://doi.org/10.3390/jcm10020211
16. Shans M, Dorgalaleh A, Safarian N, et al. Inhibitor development in patients with congenital factor VII deficiency, a study on 50 Iranian patients. Blood Coagul Fibrinolysis 2019;30:24-8. DOI: https://doi.org/10.1097/MBC.0000000000000791
How to Cite
1.
Linari S, Marino R, Leotta M, Coppola A, Di Gregorio P, Federici AB, et al. The landscape of rare coagulation factor deficiency management in Italy: a national hemophilia center survey. Bleeding Thromb Vascul Biol [Internet]. 2025 Nov. 5 [cited 2026 Jan. 28];4(3). Available from: https://www.btvb.org/btvb/article/view/369
Copyright (c) 2025 The Author(s)
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