International Registry on Factor XIII Deficiency: A basis formed mostly on European data

Vytautas Ivaskevicius; Rainer Seitz; Hans P. Kohler; Verena Schroeder; Laszlo Muszbek; Robert A. S. Ariens; Erhard Seifried; Johannes Oldenburg; and The Study Group

doi:10.1160/TH07-01-0034

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2007; 97(06): 914-921
DOI: 10.1160/TH07-01-0034

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

International Registry on Factor XIII Deficiency: A basis formed mostly on European data

Vytautas Ivaskevicius

¹Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

,

Rainer Seitz

²Paul-Ehrlich-Institute, Langen, Germany

,

Hans P. Kohler

³Laboratory for Thrombosis Research, Department of Clinical Research, Inselspital, University Hospital of Bern, Bern, Switzerland

,

Verena Schroeder

³Laboratory for Thrombosis Research, Department of Clinical Research, Inselspital, University Hospital of Bern, Bern, Switzerland

,

Laszlo Muszbek

⁴Clinical Research Center, Haemostasis, Thrombosis and Vascular Biology Research Group of the Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

,

Robert A. S. Ariens

⁵Academic Unit of Molecular Vascular Medicine, General Infirmary, Leeds, United Kingdom

,

Erhard Seifried

⁶Institute for Transfusion Medicine and Immunohaematology, Red Cross Blood Donor Service Baden-Wuerttemberg- Hessen, Frankfurt, Germany

,

Johannes Oldenburg

¹Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

⁷The Study Group*

,

and The Study Group

› Institutsangaben

Abstract

Summary

FXIII deficiency is known as one of the rarest blood coagulation disorders. In this study, the phenotypic and in part genotypic data of 104 FXIII-deficient patients recorded from 1993 – 2005 are presented. The most common bleeding symptoms were subcutaneous bleeding (57%) followed by delayed umbilical cord bleeding (56%), muscle hematoma (49%), hemorrhage after surgery (40%), hemarthrosis (36%), and intracerebral bleeding (34%). Prophylactic treatment was initiated in about 70% of all patients. FXIII-B subunit-deficient patients had a milder phenotype than patients with FXIII-A subunit deficiency. The most frequent mutation affecting the F13A gene was a splice site mutation in intron 5 (IVS5–1G>A). This mutation was found in eight (17%) of 46 analyzed families. The haplotype analysis of patients carrying the IVS5–1A allele was consistent with a founder effect. The international registry (http://www.f13-database.de) will provide clinicians and scientists working on FXIII deficiency with a helpful tool to improve patient care and direct future studies towards better understanding and treatment of the disease.

Keywords

FXIII deficiency - phenotyping - genotyping - International FXIII Registry

Volltext

Referenzen

References
1 Ichinose A. Physiopathology and regulation of factor XIII. Thromb Haemost 2001; 86: 57-65.
2 Lorand L, Losowsky MS, Miloszewski KJ. Human factor XIII: fibrin-stabilizing factor. Prog Hemost Thromb 1980; 5: 245-290.
3 Duckert F, Jung E, Schmerling DH. A hitherto undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency. Thromb Diath Haemorrh 1960; 5: 179-186.
4 Schroeder V, Meili E, Cung T. et al. Characterisation of six novel A-subunit mutations leading to congenital factor XIII deficiency and molecular analysis of the first diagnosed patient with this rare bleeding disorder. Thromb Haemost 2006; 95: 77-84.
5 Schwartz ML, Pizzo SV, Hill RL. et al. Human Factor XIII from plasma and platelets. Molecular weights, subunit structures, proteolytic activation, and crosslinking of fibrinogen and fibrin. J Biol Chem 1973; 248: 1395-1407.
6 Yee VC, Pedersen LC, Le Trong I. et al. Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII. Proc Natl Acad Sci USA 1994; 91: 7296-7300.
7 Yee VC, Pedersen LC, Bishop PD. et al. Structural evidence that the activation peptide is not released upon thrombin cleavage of factor XIII. Thromb Res 1995; 78: 389-397.
8 Ichinose A, McMullen BA, Fujikawa K. et al. Amino acid sequence of the b subunit of human factor XIII, a protein composed of ten repetitive segments. Biochemistry 1986; 25: 4633-4638.
9 Seitz R, Duckert F, Lopaciuk S. et al. ETRO Working Party on Factor XIII questionnaire on congenital factor XIII deficiency in Europe: status and perspec- tives. Study Group. Semin Thromb Hemost 1996; 22: 415-418.
10 Polymeropoulos MH, Rath DS, Xiao H. et al. Tetranucleotide repeat polymorphism at the human coagulation factor XIII A subunit gene (F13A1). Nucleic Acids Res 1991; 19: 4306.
11 Anwar R, Minford A, Gallivan L. et al. Delayed umbilical bleeding--a presenting feature for factor XIII deficiency: clinical features, genetics, and management. Pediatrics 2002; 109: E32.
12 Boda Z, Pfliegler G, Muszbek L. et al. Congenital factor XIII deficiency with multiple benign breast tumours and successful pregnancy with substitutive therapy. A case report. Haemostasis 1989; 19: 348-352.
13 Mikkola H, Syrjala M, Rasi V. et al. Deficiency in the A-subunit of coagulation factor XIII: two novel pointmutations demonstrate different effects on transcript levels. Blood 1994; 84: 517-525.
14 Mikkola H, Muszbek L, Laiho E. et al. Molecular mechanism of a mild phenotype in coagulation factor XIII (FXIII) deficiency: a splicing mutation permitting partial correct splicing of FXIII A-subunit mRNA. Blood 1997; 89: 1279-1287.
15 Girolami A, Burul A, Sticchi A. Congenital deficiency of factor XIII with normal subunit S and lack of subunit A. Report of a new family. Acta Haematol 1977; 58: 17-26.
16 Girolami A, Burul A, Fabris F. et al. Studies on factor XIII antigen in congenital factor XIII deficiency. A tentative classification of the disease in two groups. Folia Haematol Int Mag Klin Morphol Blutforsch 1978; 105: 131-141.
17 Vreken P, Niessen RW, Peters M. et al. A point mutation in an invariant splice acceptor site results in a decreased mRNA level in a patient with severe coagulation factor XIII subunit A deficiency. Thromb Haemost 1995; 74: 584-589.
18 Anwar R, Miloszewski KJ, Markham AF. New splicing mutations in the human factor XIIIA gene, each producing multiple mutant transcripts of varying abundance. Thromb Haemost 1998; 79: 1151-1156.
19 Suzuki K, Henke J, Iwata M. et al. Novel polymorphisms and haplotypes in the human coagulation factor XIII A-subunit gene. Hum Genet 1996; 98: 393-395.
20 Inbal A, Yee VC, Kornbrot N. et al. Factor XIII deficiency due to a Leu660Pro mutation in the factor XIII subunit-a gene in three unrelated Palestinian Arab families. Thromb Haemost 1997; 77: 1062-1067.
21 Anwar R, Miloszewski KJ. Factor XIII deficiency. Br J Haematol 1999; 107: 468-484.
22 Saito M, Asakura H, Yoshida T. et al. A familial factor XIII subunit B deficiency. Br J Haematol 1990; 74: 290–94. Comments in: Br J Haematol 1990; 76: 317, Br J Haematol 1991; 77: 565-566.
23 Ichinose A, Davie EW. Characterization of the gene for the a subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor. Proc Natl Acad Sci USA 1988; 85: 5829-5833.
24 Bottenus RE, Ichinose A, Davie EW. Nucleotide sequence of the gene for the b subunit of human factor XIII. Biochemistry 1990; 29: 11195-11209.
25 Anwar R, Gallivan L, Richards M, Khair K, Wright M, Minford A. Factor XIII deficiency: new nonsense and deletion mutations in the human factor XIIIA gene. Haematologica 2005; 90: 1718-1720.
26 Mikkola H, Yee VC, Syrjala M. et al. Four novel mutations in deficiency of coagulation factor XIII: consequences to expression and structure of the A-subunit. Blood 1996; 87: 141-151.
27 Takahashi N, Tsukamoto H, Umeyama H. et al. Molecular mechanisms of type II factor XIII deficiency: novel Gly562-Arg mutation and C-terminal truncation of the A subunit cause factor XIII deficiency as characterized in a mammalian expression system. Blood 1998; 91: 2830-2838.
28 Izumi T, Hashiguchi T, Castaman G. et al. A. Type I factor XIII deficiency is caused by a genetic defect of its b subunit: insertion of triplet AAC in exon III leads to premature termination in the second Sushi domain. Blood 1996; 87: 2769-2774.