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Semin Thromb Hemost 2010; 36(1): 018-033
DOI: 10.1055/s-0030-1248721
© Thieme Medical Publishers

Factor XIII and Atherothrombotic Diseases

László Muszbek1 , 2 , Zsuzsanna Bereczky1 , 2 , Zsuzsa Bagoly1 , Amir H. Shemirani2 , Éva Katona1
  • 1Clinical Research Center, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
  • 2Thrombosis, 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:
13 April 2010 (online)

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ABSTRACT

Factor XIII (FXIII) is a protransglutaminase that, after activation, cross-links fibrin chains and several plasma proteins, most importantly α2 plasmin inhibitor, to fibrin. FXIII strengthens the fibrin clot by covalent bonds and protects fibrin from the prompt elimination by the fibrinolytic system. In the last two decades, FXIII has emerged as a key regulator of fibrinolysis. FXIII is also present in platelets, monocytes, and macrophages, but this cellular form does not contribute significantly to maintaining hemostasis. FXIII deficiency is a life-threatening bleeding diathesis whose clinical consequences are well studied. In contrast, the involvement of FXIII in thrombotic disorders and its association with the risk of such diseases are less clear. This review gives an account of the data accumulated mainly in the last decade on the association of FXIII with atherothrombotic diseases and presents conclusions and hypotheses drawn from these data as well as exposing the limitations of the published studies and our knowledge on this topic. The involvement of FXIII in atherogenesis, its role in coronary artery disease, atherothrombotic ischemic stroke, and peripheral artery disease are discussed, with particular reference to the association of FXIII levels and polymorphisms with the risk of these diseases.

KEYWORDS

Cardiovascular disease - factor XIII - factor XIII ploymorphisms - peripheral artery disease - stroke

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 RW, Clowes AW, Goldhaber SZ, Marder VJ, George JN Hemostasis and Thrombosis. 4th ed. Philadelphia, PA; Lippincott Williams & Wilkins 2006: 317-334
    PubMedGoogle Scholar
  • 3 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
  • 4 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
  • 5 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
  • 6 Karimi M, Bereczky Z, Cohan N, Muszbek L. Factor XIII deficiency.  Semin Thromb Hemost. 2009;  35(4) 426-438
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 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
  • 8 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
  • 9 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
  • 10 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
  • 11 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
  • 12 Kimura S, Aoki N. Cross-linking site in fibrinogen for alpha 2-plasmin inhibitor.  J Biol Chem. 1986;  261(33) 15591-15595
    PubMedGoogle Scholar
  • 13 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
  • 14 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
  • 15 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
  • 16 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
  • 17 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
  • 18 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
  • 19 McDonagh J, Fukue H. Determinants of substrate specificity for factor XIII.  Semin Thromb Hemost. 1996;  22(5) 369-376
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 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
  • 21 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
  • 22 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
  • 23 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
  • 24 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
  • 25 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
  • 26 Muszbek L. Deficiency causing mutations and common polymorphisms in the factor XIII-A gene.  Thromb Haemost. 2000;  84(4) 524-527
    PubMedGoogle Scholar
  • 27 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
  • 28 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
  • 29 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
  • 30 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
  • 31 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
  • 32 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
  • 33 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
  • 34 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
  • 35 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
  • 36 Curtis C G, Brown K L, Credo R B et al.. Calcium-dependent unmasking of active center cysteine during activation of fibrin stabilizing factor.  Biochemistry. 1974;  13(18) 3774-3780
    CrossrefPubMedGoogle Scholar
  • 37 Board P G. Genetic polymorphism of the B subunit of human coagulation factor XIII.  Am J Hum Genet. 1980;  32(3) 348-353
    PubMedGoogle Scholar
  • 38 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
  • 39 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
  • 40 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
  • 41 Muszbek L, Adány R, Szegedi G, Polgár J, Kávai M. Factor XIII of blood coagulation in human monocytes.  Thromb Res. 1985;  37(3) 401-410
    CrossrefPubMedGoogle Scholar
  • 42 Adány R, Belkin A, Vasilevskaya T, Muszbek L. Identification of blood coagulation factor XIII in human peritoneal macrophages.  Eur J Cell Biol. 1985;  38(1) 171-173
    PubMedGoogle Scholar
  • 43 Muszbek L, Adány R, Kávai M, Boda Z, Lopaciuk S. Monocytes of patients congenitally deficient in plasma factor XIII lack factor XIII subunit a antigen and transglutaminase activity.  Thromb Haemost. 1988;  59(2) 231-235
    PubMedGoogle Scholar
  • 44 Bakker E N, Pistea A, VanBavel E. Transglutaminases in vascular biology: relevance for vascular remodeling and atherosclerosis.  J Vasc Res. 2008;  45(4) 271-278
    CrossrefPubMedGoogle Scholar
  • 45 AbdAlla S, Lother H, Langer A, el Faramawy Y, Quitterer U. Factor XIIIA transglutaminase crosslinks AT1 receptor dimers of monocytes at the onset of atherosclerosis.  Cell. 2004;  119(3) 343-354
    CrossrefPubMedGoogle Scholar
  • 46 Polgár J, Hidasi V, Muszbek L. Non-proteolytic activation of cellular protransglutaminase (placenta macrophage factor XIII).  Biochem J. 1990;  267(2) 557-560
    PubMedGoogle Scholar
  • 47 Muszbek L, Polgár J, Boda Z. Platelet factor XIII becomes active without the release of activation peptide during platelet activation.  Thromb Haemost. 1993;  69(3) 282-285
    PubMedGoogle Scholar
  • 48 Muszbek L, Haramura G, Polgár J. Transformation of cellular factor XIII into an active zymogen transglutaminase in thrombin-stimulated platelets.  Thromb Haemost. 1995;  73(4) 702-705
    PubMedGoogle Scholar
  • 49 Ma J, Liew C C. Gene profiling identifies secreted protein transcripts from peripheral blood cells in coronary artery disease.  J Mol Cell Cardiol. 2003;  35(8) 993-998
    CrossrefPubMedGoogle Scholar
  • 50 Sárváry A, Szucs S, Balogh I et al.. Possible role of factor XIII subunit A in Fcgamma and complement receptor-mediated phagocytosis.  Cell Immunol. 2004;  228(2) 81-90
    CrossrefPubMedGoogle Scholar
  • 51 Adány R, Bárdos H. Factor XIII subunit A as an intracellular transglutaminase.  Cell Mol Life Sci. 2003;  60(6) 1049-1060
    PubMedGoogle Scholar
  • 52 Bakker E N, Pistea A, Spaan J A et al.. Flow-dependent remodeling of small arteries in mice deficient for tissue-type transglutaminase: possible compensation by macrophage-derived factor XIII.  Circ Res. 2006;  99(1) 86-92
    CrossrefPubMedGoogle Scholar
  • 53 Alkjaersig N, Fletcher A P, Lewis M, Ittyerah R. Reduction of coagulation factor XIII concentration in patients with myocardial infarction, cerebral infarction, and other thromboembolic disorders.  Thromb Haemost. 1977;  38(4) 863-873
    PubMedGoogle Scholar
  • 54 Knudsen J B, Gormsen J, Skagen K, Amtorp O. Changes in platelet functions, coagulation and fibrinolysis in uncomplicated cases of acute myocardial infarction.  Thromb Haemost. 1980;  42(5) 1513-1522
    PubMedGoogle Scholar
  • 55 Nahrendorf M, Hu K, Frantz S et al.. Factor XIII deficiency causes cardiac rupture, impairs wound healing, and aggravates cardiac remodeling in mice with myocardial infarction.  Circulation. 2006;  113(9) 1196-1202
    CrossrefPubMedGoogle Scholar
  • 56 Nahrendorf M, Sosnovik D E, Waterman P et al.. Dual channel optical tomographic imaging of leukocyte recruitment and protease activity in the healing myocardial infarct.  Circ Res. 2007;  100(8) 1218-1225
    CrossrefPubMedGoogle Scholar
  • 57 Nahrendorf M, Aikawa E, Figueiredo J L et al.. Transglutaminase activity in acute infarcts predicts healing outcome and left ventricular remodelling: implications for FXIII therapy and antithrombin use in myocardial infarction.  Eur Heart J. 2008;  29(4) 445-454
    CrossrefPubMedGoogle Scholar
  • 58 Inbal A, Lubetsky A, Krapp T et al.. Impaired wound healing in factor XIII deficient mice.  Thromb Haemost. 2005;  94(2) 432-437
    PubMedGoogle Scholar
  • 59 Dardik R, Solomon A, Loscalzo J et al.. Novel proangiogenic effect of factor XIII associated with suppression of thrombospondin 1 expression.  Arterioscler Thromb Vasc Biol. 2003;  23(8) 1472-1477
    CrossrefPubMedGoogle Scholar
  • 60 Dardik R, Loscalzo J, Eskaraev R, Inbal A. Molecular mechanisms underlying the proangiogenic effect of factor XIII.  Arterioscler Thromb Vasc Biol. 2005;  25(3) 526-532
    CrossrefPubMedGoogle Scholar
  • 61 Dardik R, Leor J, Skutelsky E et al.. Evaluation of the pro-angiogenic effect of factor XIII in heterotopic mouse heart allografts and FXIII-deficient mice.  Thromb Haemost. 2006;  95(3) 546-550
    PubMedGoogle Scholar
  • 62 Dardik R, Krapp T, Rosenthal E, Loscalzo J, Inbal A. Effect of FXIII on monocyte and fibroblast function.  Cell Physiol Biochem. 2007;  19(1–4) 113-120
    CrossrefPubMedGoogle Scholar
  • 63 Vanhoutte D, Heymans S. Factor XIII: the cement of the heart after myocardial infarction?.  Eur Heart J. 2008;  29(4) 427-428
    CrossrefPubMedGoogle Scholar
  • 64 Kohler H P, Ariëns R A, Mansfield M W, Whitaker P, Grant P J. Factor XIII activity and antigen levels in patients with coronary artery disease.  Thromb Haemost. 2001;  85(3) 569-570
    PubMedGoogle Scholar
  • 65 Warner D, Mansfield M W, Grant P J. Coagulation factor XIII and cardiovascular disease in UK Asian patients undergoing coronary angiography.  Thromb Haemost. 2001;  85(3) 408-411
    PubMedGoogle Scholar
  • 66 Chatterjee T, Schroeder V, Windecker S, Meier B, Kohler H P. Venous and intracoronary factor XIII A-subunit antigen and activity levels are not associated with extent of coronary artery disease.  J Thromb Haemost. 2003;  1(4) 861-863
    CrossrefPubMedGoogle Scholar
  • 67 Warner D, Mansfield M, Grant P J. Coagulation factor XIII levels in UK Asian subjects with type 2 diabetes mellitus and coronary artery disease.  Thromb Haemost. 2001;  86(4) 1117-1118
    PubMedGoogle Scholar
  • 68 Kohler H P, Ariëns R A, Catto A J et al.. Factor XIII A-subunit concentration predicts outcome in stroke subjects and vascular outcome in healthy, middle-aged men.  Br J Haematol. 2002;  118(3) 825-832
    CrossrefPubMedGoogle Scholar
  • 69 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
  • 70 Kalaria V G, Zareba W, Moss A J The THROMBO Investigators et al. Gender-related differences in thrombogenic factors predicting recurrent cardiac events in patients after acute myocardial infarction.  Am J Cardiol. 2000;  85(12) 1401-1408
    CrossrefPubMedGoogle Scholar
  • 71 Kohler H P, Stickland M H, Ossei-Gerning N, Carter A, Mikkola H, Grant P J. Association of a common polymorphism in the factor XIII gene with myocardial infarction.  Thromb Haemost. 1998;  79(1) 8-13
    PubMedGoogle Scholar
  • 72 Wartiovaara U, Perola M, Mikkola H et al.. Association of FXIII Val34Leu with decreased risk of myocardial infarction in Finnish males.  Atherosclerosis. 1999;  142(2) 295-300
    CrossrefPubMedGoogle Scholar
  • 73 Canavy I, Henry M, Morange P E et al.. Genetic polymorphisms and coronary artery disease in the south of France.  Thromb Haemost. 2000;  83(2) 212-216
    PubMedGoogle Scholar
  • 74 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
  • 75 Franco R F, Pazin-Filho A, Tavella M H, Simões M V, Marin-Neto J A, Zago M A. Factor XIII val34leu and the risk of myocardial infarction.  Haematologica. 2000;  85(1) 67-71
    PubMedGoogle Scholar
  • 76 Gemmati D, Serino M L, Ongaro A et al.. A common mutation in the gene for coagulation factor XIII-A (VAL34Leu): a risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases.  Am J Hematol. 2001;  67(3) 183-188
    CrossrefPubMedGoogle Scholar
  • 77 Aleksic N, Ahn C, Wang Y W et al.. Factor XIIIA Val34Leu polymorphism does not predict risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) Study.  Arterioscler Thromb Vasc Biol. 2002;  22(2) 348-352
    CrossrefPubMedGoogle Scholar
  • 78 Kakko S, Elo T, Tapanainen J M, Huikuri H V, Savolainen M J. Polymorphisms of genes affecting thrombosis and risk of myocardial infarction.  Eur J Clin Invest. 2002;  32(9) 643-648
    CrossrefPubMedGoogle Scholar
  • 79 Reiner A P, Frank M B, Schwartz S M et al.. Coagulation factor XIII polymorphisms and the risk of myocardial infarction and ischaemic stroke in young women.  Br J Haematol. 2002;  116(2) 376-382
    CrossrefPubMedGoogle Scholar
  • 80 Doggen C J, Reiner A P, Vos H L, Rosendaal F R. Two factor XIII gene polymorphisms associated with a structural and functional defect and the risk of myocardial infarction in men.  J Thromb Haemost. 2003;  1(9) 2056-2058
    CrossrefPubMedGoogle Scholar
  • 81 Reiner A P, Heckbert S R, Vos H L et al.. Genetic variants of coagulation factor XIII, postmenopausal estrogen therapy, and risk of nonfatal myocardial infarction.  Blood. 2003;  102(1) 25-30
    CrossrefPubMedGoogle Scholar
  • 82 Atherosclerosis, Thrombosis, and Vascular Biology Italian Study Group . No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age.  Circulation. 2003;  107(8) 1117-1122
    CrossrefPubMedGoogle Scholar
  • 83 Butt C, Zheng H, Randell E, Robb D, Parfrey P, Xie Y G. Combined carrier status of prothrombin 20210A and factor XIII-A Leu34 alleles as a strong risk factor for myocardial infarction: evidence of a gene-gene interaction.  Blood. 2003;  101(8) 3037-3041
    CrossrefPubMedGoogle Scholar
  • 84 Roldán V, Corral J, Marín F et al.. Role of factor XIII Val34Leu polymorphism in patients <45 years of age with acute myocardial infarction.  Am J Cardiol. 2003;  91(10) 1242-1245
    CrossrefPubMedGoogle Scholar
  • 85 Hancer V S, Diz-Kucukkaya R, Bilge A K et al.. The association between factor XIII Val34Leu polymorphism and early myocardial infarction.  Circ J. 2006;  70(3) 239-242
    CrossrefPubMedGoogle Scholar
  • 86 Salazar-Sánchez L, Chaves L, Cartin M et al.. Common polymorphisms and cardiovascular factors in patients with myocardial infarction of Costa Rica.  Rev Biol Trop. 2006;  54(1) 1-11
    PubMedGoogle Scholar
  • 87 Boekholdt S M, Sandhu M S, Wareham N J, Luben R, Reitsma P H, Khaw K T. Fibrinogen plasma levels modify the association between the factor XIII Val34Leu variant and risk of coronary artery disease: the EPIC-Norfolk prospective population study.  J Thromb Haemost. 2006;  4(10) 2204-2209
    CrossrefPubMedGoogle Scholar
  • 88 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
  • 89 Mannila M N, Eriksson P, Leander K et al.. The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration.  J Intern Med. 2007;  261(2) 138-147
    PubMedGoogle Scholar
  • 90 Rallidis L S, Politou M, Komporozos C et al.. Factor XIII Val34Leu polymorphism and the risk of myocardial infarction under the age of 36 years.  Thromb Haemost. 2008;  99(6) 1085-1089
    PubMedGoogle Scholar
  • 91 Smith N L, Bis J C, Biagiotti S et al.. Variation in 24 hemostatic genes and associations with non-fatal myocardial infarction and ischemic stroke.  J Thromb Haemost. 2008;  6(1) 45-53
    PubMedGoogle Scholar
  • 92 Siegerink B, Algra A, Rosendaal F R. Genetic variants of coagulation factor XIII and the risk of myocardial infarction in young women.  Br J Haematol. 2009;  146(4) 459-461
    CrossrefPubMedGoogle Scholar
  • 93 Vokó Z, Bereczky Z, Katona E, Adány R, Muszbek L. Factor XIII Val34Leu variant protects against coronary artery disease. A meta-analysis.  Thromb Haemost. 2007;  97(3) 458-463
    PubMedGoogle Scholar
  • 94 Maitland-van der Zee A H, Peters B J, Lynch A I et al.. The effect of nine common polymorphisms in coagulation factor genes (F2, F5, F7, F12 and F13 ) on the effectiveness of statins: the GenHAT study.  Pharmacogenet Genomics. 2009;  19(5) 338-344
    CrossrefPubMedGoogle Scholar
  • 95 Roldán V, Corral J, Marín F, Rivera J, Vicente V. Effect of factor XIII VAL34LEU polymorphism on thrombolytic therapy in premature myocardial infarction.  Thromb Haemost. 2002;  88(2) 354-355
    PubMedGoogle Scholar
  • 96 Kohler H P, Mansfield M W, Clark P S, Grant P J. Interaction between insulin resistance and factor XIII Val34Leu in patients with coronary artery disease.  Thromb Haemost. 1999;  82(3) 1202-1203
    PubMedGoogle Scholar
  • 97 Collet J P, Park D, Lesty C et al.. Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed: dynamic and structural approaches by confocal microscopy.  Arterioscler Thromb Vasc Biol. 2000;  20(5) 1354-1361
    CrossrefPubMedGoogle Scholar
  • 98 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
  • 99 Bereczky Z, Balogh E, Katona E et al.. Decreased factor XIII levels in factor XIII A subunit Leu34 homozygous patients with coronary artery disease.  Thromb Res. 2008;  121(4) 469-476
    CrossrefPubMedGoogle Scholar
  • 100 Odeberg J, Freitag M, Odeberg H, Råstam L, Lindblad U. Severity of acute coronary syndrome is predicted by interactions between fibrinogen concentrations and polymorphisms in the GPIIIa and FXIII genes.  J Thromb Haemost. 2006;  4(4) 909-912
    CrossrefPubMedGoogle Scholar
  • 101 Roldán V, González-Conejero R, Marín F, Pineda J, Vicente V, Corral J. Five prothrombotic polymorphisms and the prevalence of premature myocardial infarction.  Haematologica. 2005;  90(3) 421-423
    PubMedGoogle Scholar
  • 102 Mills J D, Mansfield M W, Grant P J. Factor XIII-circulating levels and the Val34Leu polymorphism in the healthy male relatives of patients with severe coronary artery disease.  Thromb Haemost. 2002;  87(3) 409-414
    PubMedGoogle Scholar
  • 103 He J Q, Gaur L K, Stempien-Otero A et al.. Genetic variants of the hemostatic system and development of transplant coronary artery disease.  J Heart Lung Transplant. 2002;  21(6) 629-636
    CrossrefPubMedGoogle Scholar
  • 104 Rubens F D, Perry D W, Hatton M W, Bishop P D, Packham M A, Kinlough-Rathbone R L. Platelet accumulation on fibrin-coated polyethylene: role of platelet activation and factor XIII.  Thromb Haemost. 1995;  73(5) 850-856
    Article in Thieme ConnectPubMedGoogle Scholar
  • 105 Skarja G A, Brash J L, Bishop P, Woodhouse K A. Protein and platelet interactions with thermally denatured fibrinogen and cross-linked fibrin coated surfaces.  Biomaterials. 1998;  19(23) 2129-2138
    CrossrefPubMedGoogle Scholar
  • 106 Kohler H P, Futers T S, Grant P J. Prevalence of three common polymorphisms in the A-subunit gene of factor XIII in patients with coronary artery disease.  Thromb Haemost. 1999;  81(4) 511-515
    PubMedGoogle Scholar
  • 107 Kain K, Young J, Bavington J, Bamford J, Catto A J. Coagulation factor XIII B subunit antigen, FXIIIVal34Leu genotype and ischaemic stroke in South Asians.  Thromb Haemost. 2005;  93(2) 394-395
    PubMedGoogle Scholar
  • 108 Martí-Fàbregas J, Borrell M, Cocho D et al.. Hemostatic markers of recanalization in patients with ischemic stroke treated with rt-PA.  Neurology. 2005;  65(3) 366-370
    CrossrefPubMedGoogle Scholar
  • 109 Catto A J, Kohler H P, Bannan S, Stickland M, Carter A, Grant P J. Factor XIII Val 34 Leu: a novel association with primary intracerebral hemorrhage.  Stroke. 1998;  29(4) 813-816
    PubMedGoogle Scholar
  • 110 Iniesta J A, Corral J, González-Conejero R, Díaz Ortuño A, Martínez Navarro M L, Vicente V. Role of factor XIII Val 34 Leu polymorphism in patients with migraine.  Cephalalgia. 2001;  21(8) 837-841
    CrossrefPubMedGoogle Scholar
  • 111 Endler G, Funk M, Haering D et al.. Is the factor XIII 34Val/Leu polymorphism a protective factor for cerebrovascular disease?.  Br J Haematol. 2003;  120(2) 310-314
    CrossrefPubMedGoogle Scholar
  • 112 Komitopoulou A, Platokouki H, Kapsimali Z, Pergantou H, Adamtziki E, Aronis S. Mutations and polymorphisms in genes affecting hemostasis proteins and homocysteine metabolism in children with arterial ischemic stroke.  Cerebrovasc Dis. 2006;  22(1) 13-20
    CrossrefPubMedGoogle Scholar
  • 113 Akar N, Dönmez B, Deda G. FXIII gene Val34Leu polymorphism in Turkish children with cerebral infarct.  J Child Neurol. 2007;  22(2) 222-224
    CrossrefPubMedGoogle Scholar
  • 114 Pruissen D M, Slooter A J, Rosendaal F R, van der Graaf Y, Algra A. Coagulation factor XIII gene variation, oral contraceptives, and risk of ischemic stroke.  Blood. 2008;  111(3) 1282-1286
    CrossrefPubMedGoogle Scholar
  • 115 Moskau S, Smolka K, Semmler A et al.. Common genetic coagulation variants are not associated with ischemic stroke in a case-control study.  Neurol Res. 2009;  , August 5 (Epub ahead of print)
    PubMedGoogle Scholar
  • 116 Shemirani A H, Antalffy B, Pongracz E, Muszbek L. Factor XIII Val34Leu polymorphism in patients surviving or not surviving ischemic stroke.  Thromb Res. 2009;  123(Suppl 2) S157
    PubMedGoogle Scholar
  • 117 de Maat M P, Bladbjerg E M, Drivsholm T, Borch-Johnsen K, Møller L, Jespersen J. Inflammation, thrombosis and atherosclerosis: results of the Glostrup study.  J Thromb Haemost. 2003;  1(5) 950-957
    CrossrefPubMedGoogle Scholar
  • 118 Elbaz A, Poirier O, Canaple S, Chédru F, Cambien F, Amarenco P. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction.  Blood. 2000;  95(2) 586-591
    PubMedGoogle Scholar
  • 119 Slowik A, Dziedzic T, Pera J, Figlewicz D A, Szczudlik A. Coagulation factor XIII VaI34Leu polymorphism in patients with small vessel disease or primary intracerebral hemorrhage.  Cerebrovasc Dis. 2005;  19(3) 165-170
    CrossrefPubMedGoogle Scholar
  • 120 Rubattu S, Di Angelantonio E, Nitsch D et al.. Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a Sardinian population.  Thromb Haemost. 2005;  93(6) 1095-1100
    PubMedGoogle Scholar
  • 121 Muszbek L, Shemirani A H, Antalffy B, Pongracz E. Factor XIII A subunit Val34Leu polymorphism in patients surviving or not surviving ischemic stroke.  J Thromb Haemost. 2009;  7 S743
    PubMedGoogle Scholar
  • 122 Glader E L, Stegmayr B, Norrving B Riks-Stroke Collaboration et al. Sex differences in management and outcome after stroke: a Swedish national perspective.  Stroke. 2003;  34(8) 1970-1975
    CrossrefPubMedGoogle Scholar
  • 123 Di Carlo A, Lamassa M, Baldereschi M European BIOMED Study of Stroke Care Group et al. Sex differences in the clinical presentation, resource use, and 3-month outcome of acute stroke in Europe: data from a multicenter multinational hospital-based registry.  Stroke. 2003;  34(5) 1114-1119
    CrossrefPubMedGoogle Scholar
  • 124 González-Conejero R, Fernández-Cadenas I, Iniesta J A Proyecto Ictus Research Group et al. Role of fibrinogen levels and factor XIII V34L polymorphism in thrombolytic therapy in stroke patients.  Stroke. 2006;  37(9) 2288-2293
    CrossrefPubMedGoogle Scholar
  • 125 Kłoczko J, Wojtukiewicz M, Bielawiec M, Zarzycka B, Kinalska I. Plasma factor XIII and some other haemostasis parameters in patients with diabetic angiopathy.  Acta Haematol. 1986;  76(2–3) 81-85
    CrossrefPubMedGoogle Scholar
  • 126 Kłoczko J, Wojtukiewicz M, Bielawiec M, Zuch A. Alterations of haemostasis parameters with special reference to fibrin stabilization, factor XIII and fibronectin in patients with obliterative atherosclerosis.  Thromb Res. 1988;  51(6) 575-581
    CrossrefPubMedGoogle Scholar
  • 127 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
  • 128 Bhasin N, Ariens R A, West R M et al.. Altered fibrin clot structure and function in the healthy first-degree relatives of subjects with intermittent claudication.  J Vasc Surg. 2008;  48(6) 1497-1503
    CrossrefPubMedGoogle Scholar
  • 129 Renner W, Brodmann M, Pabst E, Stanger O, Wascher T C, Pilger E. The V34L polymorphism of factor XIII and peripheral arterial disease.  Int Angiol. 2002;  21(1) 53-57
    PubMedGoogle Scholar
  • 130 Weger M, Renner W, Stanger O et al.. Role of factor XIII Val34Leu polymorphism in retinal artery occlusion.  Stroke. 2001;  32(12) 2759-2761
    CrossrefPubMedGoogle Scholar

László MuszbekM.D. Ph.D. 

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

PO Box 40, H-4012 Debrecen, Hungary

Email: muszbek@med.unideb.hu

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