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Semin Thromb Hemost 2018; 44(06): 578-589
DOI: 10.1055/s-0038-1660817
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inhibitors in Hemophilia B

Cristina Santoro
1   Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy
,
Gabriele Quintavalle
2   Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Parma, Italy
,
Giancarlo Castaman
3   Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy
,
Erminia Baldacci
1   Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy
,
Antonietta Ferretti
1   Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy
,
Federica Riccardi
2   Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Parma, Italy
,
Annarita Tagliaferri
2   Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Parma, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
20 June 2018 (online)

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Abstract

Hemophilia B (HB) is an X-linked bleeding disorder caused by deficiency of factor IX (FIX). Patients with the severe form (FIX <1%) account approximately for 30 to 45% of persons with HB and usually suffer from recurrent joint, soft-tissue, and muscle bleeds. The availability of safe plasma-derived and recombinant products has virtually abolished the risk of viral infections and the adoption of prophylactic regimens has attenuated the impact of hemophilic arthropathy. Therefore, the development of an inhibitor against FIX is currently the most serious complication that can still occur in the new generations of HB patients. The development of an inhibitor in HB is a rare event (1.5–3% of all patients) but is associated with a significant morbidity, related not only to the bleeding risk but also to the frequent occurrence of allergic/anaphylactic reactions and nephrotic syndrome. Due to the relative rarity of this event, few data exist about risk factors, pathophysiology, and clinical aspects of inhibitors in HB. The induction of immune tolerance is often unsuccessful and can be otherwise affected by many complications in patients with history of allergy or anaphylaxis. Therefore, alternative therapeutic strategies and new approaches are developing. The aim of this narrative review is to discuss current knowledge about risk factors, pathophysiology, and clinical aspects of this rare but serious complication.

Keywords

hemophilia B - inhibitor - FIX - bypassing agents - anaphylaxis - nephrotic syndrome - immune tolerance induction
 

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