Download PDF
Semin Thromb Hemost 2011; 37(3): 305-314
DOI: 10.1055/s-0031-1273094
© Thieme Medical Publishers

Factor XIII and Venous Thromboembolism

Zsuzsanna Bereczky1 , László Muszbek1
  • 1Clinical Research Center and Thrombosis, Haemostasis and Vascular Biology Research Group of the Hungarian Academy of Sciences, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
Further Information

Publication History

Publication Date:
31 March 2011 (online)

    Permissions and Reprints

ABSTRACT

Plasma factor XIII (FXIII) is a tetrameric zymogen consisting of two potentially active A subunits (FXIII-A) and two carrier/inhibitory B subunits (FXIII-B). In the final phase of the coagulation cascade, FXIII is converted into an active transglutaminase (FXIIIa) by thrombin and Ca2 + . FXIIIa strengthens fibrin clot mechanically by cross-linking fibrin chains. In addition, FXIIIa is a key regulator of fibrinolysis, protecting newly formed fibrin from the fibrinolytic machinery by binding α2-plasmin inhibitor to the fibrin meshwork. FXIII is essential for maintaining hemostasis; its severe deficiency causes a life-threatening bleeding diathesis. The involvement of FXIII in thrombotic diseases and its association with the risk of these disorders is less clear. The role of FXIII in atherothrombotic diseases has been recently reviewed. This article offers a general overview of the relationship between FXIII and venous thromboembolism (VTE), to collect individual publications on this topic, present conclusions, and examine limitations of published studies. Special attention is given to the association of FXIII-A polymorphism with the risk of VTE, which has provoked considerable interest over the last decade.

KEYWORDS

Deep vein thrombosis - factor XIII - factor XIII polymorphisms - pulmonary embolism - venous thromboembolism.

REFERENCES

  • 1 Muszbek L, Yee V C, Hevessy Z. Blood coagulation factor XIII: structure and function.  Thromb Res. 1999;  94 (5) 271-305
    CrossrefPubMedGoogle Scholar
  • 2 Greenberg C S, Sane D C, Lai T-S. Factor XIII and fibrin stabilization. In: Colman R W, Clowes A W, Goldhaber S Z, Marder V J, George J N, eds. Hemostasis and Thrombosis. 4th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2006: 317-334
    Google Scholar
  • 3 Muszbek L, Bagoly Z, Bereczky Z, Katona E. The involvement of blood coagulation factor XIII in fibrinolysis and thrombosis.  Cardiovasc Hematol Agents Med Chem. 2008;  6 (3) 190-205
    CrossrefPubMedGoogle Scholar
  • 4 Grundmann U, Amann E, Zettlmeissl G, Küpper H A. Characterization of cDNA coding for human factor XIIIa.  Proc Natl Acad Sci U S A. 1986;  83 (21) 8024-8028
    CrossrefPubMedGoogle Scholar
  • 5 Ichinose A, Hendrickson L E, Fujikawa K, Davie E W. Amino acid sequence of the a subunit of human factor XIII.  Biochemistry. 1986;  25 (22) 6900-6906
    CrossrefPubMedGoogle Scholar
  • 6 Ichinose A, McMullen B A, Fujikawa K, Davie E W. Amino acid sequence of the b subunit of human factor XIII, a protein composed of ten repetitive segments.  Biochemistry. 1986;  25 (16) 4633-4638
    CrossrefPubMedGoogle Scholar
  • 7 Takahashi N, Takahashi Y, Putnam F W. Primary structure of blood coagulation factor XIIIa (fibrinoligase, transglutaminase) from human placenta.  Proc Natl Acad Sci U S A. 1986;  83 (21) 8019-8023
    CrossrefPubMedGoogle Scholar
  • 8 Weiss M S, Metzner H J, Hilgenfeld R. Two non-proline cis peptide bonds may be important for factor XIII function.  FEBS Lett. 1998;  423 (3) 291-296
    CrossrefPubMedGoogle Scholar
  • 9 Yee V C, Pedersen L C, Le Trong I, Bishop P D, Stenkamp R E, Teller D C. Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII.  Proc Natl Acad Sci U S A. 1994;  91 (15) 7296-7300
    CrossrefPubMedGoogle Scholar
  • 10 Karimi M, Bereczky Z, Cohan N, Muszbek L. Factor XIII deficiency.  Semin Thromb Hemost. 2009;  35 (4) 426-438
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Mosesson M W. Fibrinogen and fibrin structure and functions.  J Thromb Haemost. 2005;  3 (8) 1894-1904
    CrossrefPubMedGoogle Scholar
  • 12 Doolittle R F. Searching for differences between fibrinogen and fibrin that affect the initiation of fibrinolysis.  Cardiovasc Hematol Agents Med Chem. 2008;  6 (3) 181-189
    CrossrefPubMedGoogle Scholar
  • 13 Weisel J W, Litvinov R I. The biochemical and physical process of fibrinolysis and effects of clot structure and stability on the lysis rate.  Cardiovasc Hematol Agents Med Chem. 2008;  6 (3) 161-180
    CrossrefPubMedGoogle Scholar
  • 14 Chen R, Doolittle R F. - cross-linking sites in human and bovine fibrin.  Biochemistry. 1971;  10 (24) 4487-4491
    PubMedGoogle Scholar
  • 15 Gladner J A, Nossal R. Effects of crosslinking on the rigidity and proteolytic susceptibility of human fibrin clots.  Thromb Res. 1983;  30 (3) 273-288
    CrossrefPubMedGoogle Scholar
  • 16 Standeven K F, Carter A M, Grant P J et al.. Functional analysis of fibrin gamma-chain cross-linking by activated factor XIII: determination of a cross-linking pattern that maximizes clot stiffness.  Blood. 2007;  110 (3) 902-907
    CrossrefPubMedGoogle Scholar
  • 17 Siebenlist K R, Mosesson M W. Evidence of intramolecular cross-linked A alpha.gamma chain heterodimers in plasma fibrinogen.  Biochemistry. 1996;  35 (18) 5817-5821
    CrossrefPubMedGoogle Scholar
  • 18 Mosesson M W, Siebenlist K R, Amrani D L, DiOrio J P. Identification of covalently linked trimeric and tetrameric D domains in crosslinked fibrin.  Proc Natl Acad Sci U S A. 1989;  86 (4) 1113-1117
    CrossrefPubMedGoogle Scholar
  • 19 Siebenlist K R, Mosesson M W. Progressive cross-linking of fibrin gamma chains increases resistance to fibrinolysis.  J Biol Chem. 1994;  269 (45) 28414-28419
    PubMedGoogle Scholar
  • 20 Gaffney P J, Whitaker A N. Fibrin crosslinks and lysis rates.  Thromb Res. 1979;  14 (1) 85-94
    CrossrefPubMedGoogle Scholar
  • 21 Francis C W, Marder V J. Increased resistance to plasmic degradation of fibrin with highly crosslinked alpha-polymer chains formed at high factor XIII concentrations.  Blood. 1988;  71 (5) 1361-1365
    PubMedGoogle Scholar
  • 22 Francis C W, Marder V J. Rapid formation of large molecular weight alpha-polymers in cross-linked fibrin induced by high factor XIII concentrations. Role of platelet factor XIII.  J Clin Invest. 1987;  80 (5) 1459-1465
    CrossrefPubMedGoogle Scholar
  • 23 McDonagh Jr R P, McDonagh J, Duckert F. The influence of fibrin crosslinking on the kinetics of urokinase-induced clot lysis.  Br J Haematol. 1971;  21 (3) 323-332
    CrossrefPubMedGoogle Scholar
  • 24 Sakata Y, Aoki N. Cross-linking of alpha 2-plasmin inhibitor to fibrin by fibrin-stabilizing factor.  J Clin Invest. 1980;  65 (2) 290-297
    CrossrefPubMedGoogle Scholar
  • 25 Lee K N, Jackson K W, Christiansen V J, Chung K H, McKee P A. A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion.  Blood. 2004;  103 (10) 3783-3788
    CrossrefPubMedGoogle Scholar
  • 26 Sumi Y, Ichikawa Y, Nakamura Y, Miura O, Aoki N. Expression and characterization of pro alpha 2-plasmin inhibitor.  J Biochem. 1989;  106 (4) 703-707
    PubMedGoogle Scholar
  • 27 Bangert K, Johnsen A H, Christensen U, Thorsen S. Different N-terminal forms of alpha 2-plasmin inhibitor in human plasma.  Biochem J. 1993;  291 (Pt 2) 623-625
    PubMedGoogle Scholar
  • 28 Lee K N, Jackson K W, Christiansen V J, Lee C S, Chun J G, McKee P A. Why alpha-antiplasmin must be converted to a derivative form for optimal function.  J Thromb Haemost. 2007;  5 (10) 2095-2104
    CrossrefPubMedGoogle Scholar
  • 29 Kimura S, Aoki N. Cross-linking site in fibrinogen for alpha 2-plasmin inhibitor.  J Biol Chem. 1986;  261 (33) 15591-15595
    PubMedGoogle Scholar
  • 30 Sakata Y, Aoki N. Significance of cross-linking of alpha 2-plasmin inhibitor to fibrin in inhibition of fibrinolysis and in hemostasis.  J Clin Invest. 1982;  69 (3) 536-542
    CrossrefPubMedGoogle Scholar
  • 31 Mosesson M W, Siebenlist K R, Hernandez I, Lee K N, Christiansen V J, McKee P A. Evidence that alpha2-antiplasmin becomes covalently ligated to plasma fibrinogen in the circulation: a new role for plasma factor XIII in fibrinolysis regulation.  J Thromb Haemost. 2008;  6 (9) 1565-1570
    CrossrefPubMedGoogle Scholar
  • 32 Kimura S, Tamaki T, Aoki N. Acceleration of fibrinolysis by the N-terminal peptide of alpha 2-plasmin inhibitor.  Blood. 1985;  66 (1) 157-160
    PubMedGoogle Scholar
  • 33 Jansen J W, Haverkate F, Koopman J, Nieuwenhuis H K, Kluft C, Boschman T A. Influence of factor XIIIa activity on human whole blood clot lysis in vitro.  Thromb Haemost. 1987;  57 (2) 171-175
    PubMedGoogle Scholar
  • 34 Carpenter S L, Mathew P. Alpha2-antiplasmin and its deficiency: fibrinolysis out of balance.  Haemophilia. 2008;  14 (6) 1250-1254
    CrossrefPubMedGoogle Scholar
  • 35 Lee K N, Lee S C, Jackson K W, Tae W C, Schwartzott D G, McKee P A. Effect of phenylglyoxal-modified alpha2-antiplasmin on urokinase-induced fibrinolysis.  Thromb Haemost. 1998;  80 (4) 637-644
    PubMedGoogle Scholar
  • 36 Lee K N, Tae W C, Jackson K W, Kwon S H, McKee P A. Characterization of wild-type and mutant alpha2-antiplasmins: fibrinolysis enhancement by reactive site mutant.  Blood. 1999;  94 (1) 164-171
    PubMedGoogle Scholar
  • 37 Jansen I, Olesen J, Edvinsson L. 5-Hydroxytryptamine receptor characterization of human cerebral, middle meningeal and temporal arteries: regional differences.  Acta Physiol Scand. 1993;  147 (2) 141-150
    CrossrefPubMedGoogle Scholar
  • 38 Valnickova Z, Enghild J J. Human procarboxypeptidase U, or thrombin-activable fibrinolysis inhibitor, is a substrate for transglutaminases. Evidence for transglutaminase-catalyzed cross-linking to fibrin.  J Biol Chem. 1998;  273 (42) 27220-27224
    CrossrefPubMedGoogle Scholar
  • 39 Bendixen E, Borth W, Harpel P C. Transglutaminases catalyze cross-linking of plasminogen to fibronectin and human endothelial cells.  J Biol Chem. 1993;  268 (29) 21962-21967
    PubMedGoogle Scholar
  • 40 Bendixen E, Harpel P C, Sottrup-Jensen L. Location of the major epsilon-(gamma-glutamyl)lysyl cross-linking site in transglutaminase-modified human plasminogen.  J Biol Chem. 1995;  270 (30) 17929-17933
    CrossrefPubMedGoogle Scholar
  • 41 McDonagh J, Fukue H. Determinants of substrate specificity for factor XIII.  Semin Thromb Hemost. 1996;  22 (5) 369-376
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Reed G L, Houng A K. The contribution of activated factor XIII to fibrinolytic resistance in experimental pulmonary embolism.  Circulation. 1999;  99 (2) 299-304
    CrossrefPubMedGoogle Scholar
  • 43 Bagoly Z, Haramura G, Muszbek L. Down-regulation of activated factor XIII by polymorphonuclear granulocyte proteases within fibrin clot.  Thromb Haemost. 2007;  98 (2) 359-367
    PubMedGoogle Scholar
  • 44 Bagoly Z, Fazakas F, Komáromi I, Haramura G, Tóth E, Muszbek L. Cleavage of factor XIII by human neutrophil elastase results in a novel active truncated form of factor XIII A subunit.  Thromb Haemost. 2008;  99 (4) 668-674
    PubMedGoogle Scholar
  • 45 Robinson B R, Houng A K, Reed G L. Catalytic life of activated factor XIII in thrombi. Implications for fibrinolytic resistance and thrombus aging.  Circulation. 2000;  102 (10) 1151-1157
    CrossrefPubMedGoogle Scholar
  • 46 Kłoczko J, Wojtukiewicz M, Bielawiec M. Molecular subunits and transamidase activity of factor XIII in patients with deep vein thrombosis.  Folia Haematol Int Mag Klin Morphol Blutforsch. 1986;  113 (6) 810-814
    PubMedGoogle Scholar
  • 47 Kucher N, Schroeder V, Kohler H P. Role of blood coagulation factor XIII in patients with acute pulmonary embolism. Correlation of factor XIII antigen levels with pulmonary occlusion rate, fibrinogen, D-dimer, and clot firmness.  Thromb Haemost. 2003;  90 (3) 434-438
    PubMedGoogle Scholar
  • 48 Van Hylckama Vlieg A, Komanasin N, Ariëns R A et al.. Factor XIII Val34Leu polymorphism, factor XIII antigen levels and activity and the risk of deep venous thrombosis.  Br J Haematol. 2002;  119 (1) 169-175
    CrossrefPubMedGoogle Scholar
  • 49 Cushman M, O'Meara E S, Folsom A R, Heckbert S R. Coagulation factors IX through XIII and the risk of future venous thrombosis: the Longitudinal Investigation of Thromboembolism Etiology.  Blood. 2009;  114 (14) 2878-2883
    CrossrefPubMedGoogle Scholar
  • 50 Bereczky Z, Balogh E, Katona E, Czuriga I, Edes I, Muszbek L. Elevated factor XIII level and the risk of myocardial infarction in women.  Haematologica. 2007;  92 (2) 287-288
    CrossrefPubMedGoogle Scholar
  • 51 Shemirani A H, Szomják E, Csiki Z, Katona E, Bereczky Z, Muszbek L. Elevated factor XIII level and the risk of peripheral artery disease.  Haematologica. 2008;  93 (9) 1430-1432
    CrossrefPubMedGoogle Scholar
  • 52 Mikkola H, Syrjälä M, Rasi V et al.. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels.  Blood. 1994;  84 (2) 517-525
    PubMedGoogle Scholar
  • 53 Muszbek L. Deficiency causing mutations and common polymorphisms in the factor XIII-A gene.  Thromb Haemost. 2000;  84 (4) 524-527
    PubMedGoogle Scholar
  • 54 Wartiovaara U, Mikkola H, Szôke G et al.. Effect of Val34Leu polymorphism on the activation of the coagulation factor XIII-A.  Thromb Haemost. 2000;  84 (4) 595-600
    PubMedGoogle Scholar
  • 55 Balogh I, Szôke G, Kárpáti L et al.. Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia.  Blood. 2000;  96 (7) 2479-2486
    PubMedGoogle Scholar
  • 56 Ariëns R A, Philippou H, Nagaswami C, Weisel J W, Lane D A, Grant P J. The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure.  Blood. 2000;  96 (3) 988-995
    CrossrefPubMedGoogle Scholar
  • 57 Shemirani A H, Haramura G, Bagoly Z, Muszbek L. The combined effect of fibrin formation and factor XIII A subunit Val34Leu polymorphism on the activation of factor XIII in whole plasma.  Biochim Biophys Acta. 2006;  1764 (8) 1420-1423
    PubMedGoogle Scholar
  • 58 Schröder V, Kohler H P. Effect of factor XIII Val34Leu on alpha2-antiplasmin incorporation into fibrin.  Thromb Haemost. 2000;  84 (6) 1128-1130
    PubMedGoogle Scholar
  • 59 Lim B C, Ariëns R A, Carter A M, Weisel J W, Grant P J. Genetic regulation of fibrin structure and function: complex gene-environment interactions may modulate vascular risk.  Lancet. 2003;  361 (9367) 1424-1431
    CrossrefPubMedGoogle Scholar
  • 60 Lee I H, Chung S I, Lee S Y. Effects of Val34Leu and Val35Leu polymorphism on the enzyme activity of the coagulation factor XIII-A.  Exp Mol Med. 2002;  34 (5) 385-390
    PubMedGoogle Scholar
  • 61 Anwar R, Gallivan L, Edmonds S D, Markham A F. Genotype/phenotype correlations for coagulation factor XIII: specific normal polymorphisms are associated with high or low factor XIII specific activity.  Blood. 1999;  93 (3) 897-905
    PubMedGoogle Scholar
  • 62 Gallivan L, Markham A F, Anwar R. The Leu564 factor XIIIA variant results in significantly lower plasma factor XIII levels than the Pro564 variant.  Thromb Haemost. 1999;  82 (4) 1368-1370
    PubMedGoogle Scholar
  • 63 Catto A J, Kohler H P, Coore J, Mansfield M W, Stickland M H, Grant P J. Association of a common polymorphism in the factor XIII gene with venous thrombosis.  Blood. 1999;  93 (3) 906-908
    PubMedGoogle Scholar
  • 64 Renner W, Köppel H, Hoffmann C et al.. Prothrombin G20210A, factor V Leiden, and factor XIII Val34Leu: common mutations of blood coagulation factors and deep vein thrombosis in Austria.  Thromb Res. 2000;  99 (1) 35-39
    CrossrefPubMedGoogle Scholar
  • 65 Franco R F, Reitsma P H, Lourenço D et al.. Factor XIII Val34Leu is a genetic factor involved in the etiology of venous thrombosis.  Thromb Haemost. 1999;  81 (5) 676-679
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Alhenc-Gelas M, Reny J L, Aubry M L, Aiach M, Emmerich J. The FXIII Val 34 Leu mutation and the risk of venous thrombosis.  Thromb Haemost. 2000;  84 (6) 1117-1118
    PubMedGoogle Scholar
  • 67 Corral J, González-Conejero R, Iniesta J A, Rivera J, Martínez C, Vicente V. The FXIII Val34Leu polymorphism in venous and arterial thromboembolism.  Haematologica. 2000;  85 (3) 293-297
    PubMedGoogle Scholar
  • 68 Margaglione M, Bossone A, Brancaccio V, Ciampa A, Di Minno G. Factor XIII Val34Leu polymorphism and risk of deep vein thrombosis.  Thromb Haemost. 2000;  84 (6) 1118-1119
    PubMedGoogle Scholar
  • 69 Ramacciotti E, Wolosker N, Puech-Leao P et al.. Prevalence of factor V Leiden, FII G20210A, FXIII Val34Leu and MTHFR C677T polymorphisms in cancer patients with and without venous thrombosis.  Thromb Res. 2003;  109 (4) 171-174
    CrossrefPubMedGoogle Scholar
  • 70 Carter A M, Catto A J, Kohler H P, Ariëns R A, Stickland M H, Grant P J. alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism.  Blood. 2000;  96 (3) 1177-1179
    PubMedGoogle Scholar
  • 71 Zidane M, de Visser M C, ten Wolde M et al.. Frequency of the TAFI -438 G/A and factor XIIIA Val34Leu polymorphisms in patients with objectively proven pulmonary embolism.  Thromb Haemost. 2003;  90 (3) 439-445
    PubMedGoogle Scholar
  • 72 Wells P S, Anderson J L, Scarvelis D K, Doucette S P, Gagnon F. Factor XIII Val34Leu variant is protective against venous thromboembolism: a HuGE review and meta-analysis.  Am J Epidemiol. 2006;  164 (2) 101-109
    CrossrefPubMedGoogle Scholar
  • 73 Salazar-Sánchez L, Leon M P, Cartin M et al.. The FXIIIVal34Leu, common and risk factors of venous thrombosis in early middle-age Costa Rican patients.  Cell Biochem Funct. 2007;  25 (6) 739-745
    CrossrefPubMedGoogle Scholar
  • 74 Rasmussen-Torvik L J, Cushman M, Tsai M Y et al.. The association of alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism in the LITE study.  Thromb Res. 2007;  121 (1) 1-7
    CrossrefPubMedGoogle Scholar
  • 75 Wells P S, Anderson J L, Rodger M A, Carson N, Grimwood R L, Doucette S P. The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?.  Blood Coagul Fibrinolysis. 2006;  17 (7) 533-538
    CrossrefPubMedGoogle Scholar
  • 76 Le Gal G, Delahousse B, Lacut K Groupe d'Etudes sur la Thrombose des Hôpitaux Universitaires du Grand Ouest et al. Fibrinogen Aalpha-Thr312Ala and factor XIII-A Val34Leu polymorphisms in idiopathic venous thromboembolism.  Thromb Res. 2007;  121 (3) 333-338
    CrossrefPubMedGoogle Scholar
  • 77 Cushman M, Cornell A, Folsom A R et al.. Associations of the beta-fibrinogen Hae III and factor XIII Val34Leu gene variants with venous thrombosis.  Thromb Res. 2007;  121 (3) 339-345
    CrossrefPubMedGoogle Scholar
  • 78 Suntharalingam J, Goldsmith K, van Marion V et al.. Fibrinogen Aalpha Thr312Ala polymorphism is associated with chronic thromboembolic pulmonary hypertension.  Eur Respir J. 2008;  31 (4) 736-741
    CrossrefPubMedGoogle Scholar
  • 79 Gohil R, Peck G, Sharma P. The genetics of venous thromboembolism. A meta-analysis involving approximately 120,000 cases and 180,000 controls.  Thromb Haemost. 2009;  102 (2) 360-370
    Article in Thieme ConnectPubMedGoogle Scholar
  • 80 Undas A, Zawilska K, Ciesla-Dul M et al.. Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives.  Blood. 2009;  114 (19) 4272-4278
    CrossrefPubMedGoogle Scholar
  • 81 Diz-Kucukkaya R, Hancer V S, Inanc M, Nalcaci M, Pekcelen Y. Factor XIII Val34Leu polymorphism does not contribute to the prevention of thrombotic complications in patients with antiphospholipid syndrome.  Lupus. 2004;  13 (1) 32-35
    CrossrefPubMedGoogle Scholar
  • 82 de la Red G, Tàssies D, Espinosa G et al.. Factor XIII-A subunit Val34Leu polymorphism is associated with the risk of thrombosis in patients with antiphospholipid antibodies and high fibrinogen levels.  Thromb Haemost. 2009;  101 (2) 312-316
    PubMedGoogle Scholar
  • 83 Franco R F, Middeldorp S, Meinardi J R, van Pampus E C, Reitsma P H. Factor XIII Val34Leu and the risk of venous thromboembolism in factor V Leiden carriers.  Br J Haematol. 2000;  111 (1) 118-121
    CrossrefPubMedGoogle Scholar
  • 84 Morange P E, Henry M, Brunet D, Aillaud M F, Juhan-Vague I. Factor XIIIV34L is not an additional genetic risk for venous thrombosis in factor V Leiden carriers.  Blood. 2001;  97 (6) 1894-1895
    CrossrefPubMedGoogle Scholar
  • 85 Vossen C Y, Rosendaal F R. The protective effect of the factor XIII Val34Leu mutation on the risk of deep venous thrombosis is dependent on the fibrinogen level.  J Thromb Haemost. 2005;  3 (5) 1102-1103
    CrossrefPubMedGoogle Scholar
  • 86 Bereczky Z, Balogh E, Katona E et al.. Modulation of the risk of coronary sclerosis/myocardial infarction by the interaction between factor XIII subunit A Val34Leu polymorphism and fibrinogen concentration in the high risk Hungarian population.  Thromb Res. 2007;  120 (4) 567-573
    CrossrefPubMedGoogle Scholar
  • 87 Komanasin N, Catto A J, Futers T S, van Hylckama Vlieg A, Rosendaal F R, Ariëns R A. A novel polymorphism in the factor XIII B-subunit (His95Arg): relationship to subunit dissociation and venous thrombosis.  J Thromb Haemost. 2005;  3 (11) 2487-2496
    CrossrefPubMedGoogle Scholar
  • 88 Ryan A W, Hughes D A, Tang K et al.. Natural selection and the molecular basis of electrophoretic variation at the coagulation F13B locus.  Eur J Hum Genet. 2009;  17 (2) 219-227
    CrossrefPubMedGoogle Scholar
  • 89 Iwata H, Kitano T, Umetsu K et al.. Distinct C-terminus of the B subunit of factor XIII in a population-associated major phenotype: the first case of complete allele-specific alternative splicing products in the coagulation and fibrinolytic systems.  J Thromb Haemost. 2009;  7 (7) 1084-1091
    CrossrefPubMedGoogle Scholar

László MuszbekM.D. Ph.D. 

Clinical Research Center, University of Debrecen, Medical and Health Science Center

P.O. Box 40, H-4012 Debrecen, Hungary

Email: muszbek@med.unideb.hu

      >