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DOI: 10.1160/TH14-11-0952
Factor XIII-A dynamics in acute myocardial infarction: a novel prognostic biomarker?
Financial support: The present project has been funded by ALT (Italian Association Against Thrombosis and Cardiovascular Disease) and Italian MIUR.Publikationsverlauf
Received:
17. November 2014
Accepted after major revision:
23. Februar 2015
Publikationsdatum:
22. November 2017 (online)
Summary
After acute myocardial infarction (MI) the damaged heart has to be repaired. Factor XIII (FXIII) is considered a key molecule in promoting heart healing. FXIII deficiency was associated to cardiac rupture and anomalous remodelling in MI. During MI, FXIII contributes firstly to the intracoronary thrombus formation and shortly after to heal the myocardial lesion. To quantify the real contribution of FXIII in this process, and to explore its possible prognostic role, we monitored the FXIII-A subunit levels in 350 acute MI patients during the first six days (d0-d5) plus a control at 30–60 days (d30). A one-year follow-up was performed for all the patients. A transient drop in the FXIII-A mean level was noted in the whole cohort of patients (FXIII-Ad0 99.48 ± 30.5 vs FXIII-Ad5 76.51 ± 27.02; p< 0.0001). Interestingly, those who developed post-MI heart failure showed the highest drop (FXIII-Ad5 52.1 ± 25.2) and they already presented with low levels at recruitment. Similarly, those who died showed the same FXIII-A dynamic (FXIII-Ad5 54.0 ± 22.5). Conversely, patients who remained free of major adverse cardiac events, had lower consuming (FXIII-Ad0 103.6 ± 29.1 vs FXIII-Ad5 84.4 ± 24.5; p< 0.0001). Interestingly, the FXIII-A drop was independent from the amount of injury assessed by TnT and CKMB levels. The survival analysis ascribed an increased probability of early death or heart failure inversely related to FXIII-A quartiles (FXIII-A25th< 59.5 %; hazard ratio 4.25; 2.2–5.1; p< 0.0001). Different FXIII-A dynamics and levels could be utilised as early prognostic indicators during acute MI, revealing the individual potential to heal and suggesting tailored treatments to avoid heart failure or its extreme consequence.
Note: This paper was presented in part at the 14th Congress of the International Society on Thrombosis and Haemostasis, Amsterdam, Netherlands, June 29 – July 24, 2013.
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References
- 1 Nahrendorf M, Pittet MJ, Swirski FK. Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. Circulation 2010; 121: 2437-2445.
- 2 American Heart Association.. Cardiovascular Disease Statistics. Available at: http://www.americanheart.org/presenter.jhtml?identifier_4478 Accessed August 20, 2009.
- 3 National Heart, Lung, and Blood Institute.. NHLBI Financial Year 2008 Fact Book. Available at: http://www.nhlbi.nih.gov/about/factbook/toc.htm Accessed August 20, 2009.
- 4 Chien KR, Domian IJ, Parker KK. Cardiogenesis and the complex biology of regenerative cardiovascular medicine. Science 2008; 322: 1494-1497.
- 5 Ertl G, Frantz S. Healing after myocardial infarction. Cardiovasc Res 2005; 66: 22-32.
- 6 Nahrendorf M. Imaging of infarct healing predicts left ventricular remodeling and evolution of heart failure: focus on protease activity. Circ Cardiovasc Imaging 2011; 04: 351-353.
- 7 Bagoly Z, Koncz Z, Harsfalvi J. et al. Factor XIII. clot structure, thrombosis. Thromb Res 2012; 129: 382-387.
- 8 Ichinose A. Factor XIII is a key molecule at the intersection of coagulation and fibrinolysis as well as inflammation and infection control. Int J Hematol 2012; 95: 362-370.
- 9 Gemmati D, Tognazzo S, Serino ML. et al. Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension. Wound Repair Regen 2004; 12: 512-517.
- 10 Gemmati D, Tognazzo S, Catozzi L. et al. Influence of gene polymorphisms in ulcer healing process after superficial venous surgery. J Vasc Surg 2006; 44: 554-562.
- 11 Zamboni P, De Mattei M, Ongaro A. et al. Factor XIII contrasts the effects of metalloproteinases in human dermal fibroblast cultured cells. Vasc Endovascular Surg 2004; 38: 431-438.
- 12 Inbal A, Dardik R. Role of coagulation factor XIII (FXIII) in angiogenesis and tissue repair. Pathophysiol Haemost Thromb 2006; 35: 162-165.
- 13 Nahrendorf M, Swirski FK, Aikawa E. et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 2007; 204: 3037-3047.
- 14 Panizzi P, Swirski FK, Figueiredo JL. et al. Impaired infarct healing in athero-sclerotic mice with Ly-6C(hi) monocytosis. J Am Coll Cardiol 2010; 55: 1629-1638.
- 15 Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 2013; 339: 161-166.
- 16 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: 1196-1202.
- 17 Nahrendorf M, Weissleder R, Ertl G. Does FXIII deficiency impair wound healing after myocardial infarction?. PLoS One 2006; 01: 48.
- 18 Nahrendorf M, Aikawa E, Figueiredo JL. 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: 445-454.
- 19 Vanhoutte D, Heymans S. Factor XIII: the cement of the heart after myocardial infarction?. Eur Heart J 2008; 29: 427-428.
- 20 Mukherjee R, Zavadzkas JA, Saunders SM. et al. Targeted myocardial microinjections of a biocomposite material reduces infarct expansion in pigs. Ann Thorac Surg 2008; 86: 1268-1276.
- 21 Della Rocca DG, Willenberg BJ, Ferreira LF. et al. A degradable, bioactive, gelatinized alginate hydrogel to improve stem cell/growth factor delivery and facilitate healing after myocardial infarction. Med Hypotheses 2012; 79: 673-677.
- 22 Jaffer FA, Sosnovik DE, Nahrendorf M. et al. Molecular imaging of myocardial infarction. J Mol Cell Cardiol 2006; 41: 921-933.
- 23 McCarthy JR, Patel P, Botnaru I. et al. Multimodal nanoagents for the detection of intravascular thrombi. Bioconjug Chem 2009; 20: 1251-1255.
- 24 Alkjaersig N, Fletcher AP, Lewis M. et al. Reduction of coagulation factor XIII concentration in patients with myocardial infarction, cerebral infarction, and other thromboembolic disorders. Thromb Haemost 1977; 38: 863-873.
- 25 Fletcher AP, Alkjaersig NK, Ghani FM. et al. Blood coagulation system patho-physiology in acute myocardial infarction: the influence of anticoagulant treatment on laboratory findings. J Lab Clin Med 1979; 93: 1054-1065.
- 26 Kohler HP, Ariens RA, Catto AJ. 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: 825-832.
- 27 Kucher N, Schroeder V, Kohler HP. 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: 434-438.
- 28 Chatterjee T, Schroeder V, Windecker S. et al. Venous and intracoronary factor XIII A-subunit antigen and activity levels are not associated with extent of coronary artery disease. J Thromb Haemost 2003; 01: 861-863.
- 29 Gemmati D, Federici F, Campo G. et al. Factor XIIIA-V34L and factor XIIIB-H95R gene variants: effects on survival in myocardial infarction patients. Mol Med 2007; 13: 112-120.
- 30 Schroeder V, Ortner E, Mono ML. et al. Coagulation factor XIII activation peptide and subunit levels in patients with acute ischaemic stroke: a pilot study. Thromb Res 2010; 126: 122-127.
- 31 Voko Z, Bereczky Z, Katona E. et al. Factor XIII Val34Leu variant protects against coronary artery disease. A meta-analysis. Thromb Haemost 2007; 97: 458-463.
- 32 Manzoli A, Andreotti F, Leone AM. et al. Vascular and haemostatic gene polymorphisms associated with non-fatal myocardial infarction: a critical review. Ital Heart J 2000; 01: 184-193.
- 33 Gemmati D, Serino ML, 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: 183-188.
- 34 Bereczky Z, Balogh E, Katona E. et al. Elevated factor XIII level and the risk of myocardial infarction in women. Haematologica 2007; 92: 287-288.
- 35 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: 469-476.
- 36 Mezei ZA, Bereczky Z, Katona E. et al. Factor XIII B Subunit Polymorphisms and the Risk of Coronary Artery Disease. Int J Mol Sci 2015; 16: 1143-1159.
- 37 Thygesen K, Alpert JS, Jaffe AS. et al. Third universal definition of myocardial infarction. Eur Heart J 2012; 33: 2551-2567.
- 38 Chia S, Senatore F, Raffel OC. et al. Utility of cardiac biomarkers in predicting infarct size, left ventricular function, and clinical outcome after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 2008; 01: 415-423.
- 39 Bohmer E, Hoffmann P, Abdelnoor M. et al. Troponin T concentration 3 days after acute ST-elevation myocardial infarction predicts infarct size and cardiac function at 3 months. Cardiology 2009; 113: 207-212.
- 40 Li XH, Zhou X, Zeng S. et al. Effects of intramyocardial injection of platelet-rich plasma on the healing process after myocardial infarction. Coron Artery Dis 2008; 19: 363-370.
- 41 Wehberg KE, Answini G, Wood D. et al. Intramyocardial injection of autologous platelet-rich plasma combined with transmyocardial revascularisation. Cell Transplant 2009; 18: 353-359.
- 42 Mishra A, Velotta J, Brinton TJ. et al. RevaTen platelet-rich plasma improves cardiac function after myocardial injury. Cardiovasc Revasc Med 2011; 12: 158-163.
- 43 Hoppe B. Fibrinogen and factor XIII at the intersection of coagulation, fibrinolysis and inflammation. Thromb Haemost 2014; 112: 649-658.
- 44 Bockeria LA, Samsonova NN, Yurlov IA. et al. Dynamics of factor XIII levels after open heart surgery for congenital heart defects: do cyanotic and acyanotic patients differ?. Pediatr Cardiol 2014; 35: 1108-1115.