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Semin Thromb Hemost 2017; 43(01): 059-068
DOI: 10.1055/s-0036-1585076
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Developing the First Recombinant Factor XIII for Congenital Factor XIII Deficiency: Clinical Challenges and Successes

Manuel Carcao
1   Division of Haematology/Oncology, Department of Paediatrics and Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Canada
,
Katsuyuki Fukutake
2   Department of Laboratory Medicine, Tokyo Medical University, Tokyo, Japan
,
Aida Inbal
3   Thrombosis and Hemostasis Unit, Rabin Medical Center, Petah Tikva, Israel
4   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Bryce Kerlin
5   Nationwide Children's Hospital, The Ohio State University College of Medicine, Ohio
,
Riitta Lassila
6   Coagulation Disorders Unit, Hematology and Cancer Center and Clinical Chemistry, Helsinki University Hospital, Helsinki, Finland
,
Johannes Oldenburg
7   Institute for Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany
,
May-Lill Garly
8   Novo Nordisk A/S, Søborg, Denmark
,
Diane Nugent
9   Children's Hospital of Orange County, UC Irvine School of Medicine, Orange, California
› Author Affiliations
Further Information

Publication History

Publication Date:
24 August 2016 (online)

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Abstract

Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder with potentially life-threatening consequences. FXIII is composed of two subunits (A and B), and a deficiency or dysfunction of either can result in FXIII deficiency. Traditionally, FXIII deficiency has been managed by infusing plasma-derived products containing FXIII (fresh frozen plasma, cryoprecipitate, and plasma-derived FXIII concentrates), all of which contain both subunits. Despite the increased safety of plasma-derived products, concern remains regarding potential viral safety issues. This review describes the development, from concept to clinical use, of a recombinant FXIII molecule (containing subunit A only; rFXIII-A2) for congenital FXIII-A subunit deficiency. Unmet needs and ongoing challenges in congenital FXIII deficiency are also discussed. Despite the challenges in developing a product for a very rare bleeding disorder, the information gathered on efficacy, safety, and pharmacokinetics of FXIII replacement therapy represents the largest dataset on congenital FXIII-A subunit deficiency in the world. It also provides evidence for the safety and efficacy of monthly prophylaxis with 35 IU/kg of rFXIII-A2 in patients with FXIII-A subunit deficiency. The issues encountered and overcome, along with lessons learned, may be applied to and encourage the development of new recombinant products for other rare bleeding disorders.

Keywords

congenital FXIII deficiency - recombinant factor XIII - prophylaxis
 

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