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Assessment of thrombin-activatable fibrinolysis inhibitor levels in essential hypertension

Year 2024, EARLY ONLINE, 1 - 10
https://doi.org/10.18621/eurj.1501230

Abstract

Objectives: Most research in this field has highlighted the significance of the fibrinolytic system in essential hypertension, revealing anomalies within the coagulation and fibrinolytic pathways that contribute to a hypercoagulable condition. We aim to investigate thrombin-activatable fibrinolysis inhibitor (TAFI) levels in individuals diagnosed with high blood pressure.

Methods: We compared 40 newly diagnosed cases of essential hypertension, who were not receiving antihypertensive medication, with 40 normotensive individuals as controls. Various parameters and TAFI levels were assessed in all subjects and compared between the groups. Additionally, hypertensive patients were classified based on whether they exhibited high or normal cholesterol levels (≥200 mg/dL).

Results: The concentrations of TAFI were significantly higher in the hypertensive cohort compared to the normotensive counterparts (116.95±29.76 and 77.72±32.78 (ng/mL) , respectively; P<0.001). In addition, the high blood pressure cohort exhibited a notably higher mean body mass index (BMI) in contrast to the normotensive group (29.55±4.82 vs. 24.93±3.07 kg/m2, respectively; P<0.001). On the other hand, the remaining results showed no statistically significant differences between the two cohorts. Linear regression analysis revealed that blood pressure status and BMI independently correlated with plasma TAFI levels.

Conclusions: The concentrations of TAFI are elevated in patients with high blood pressure compared to individuals with normal blood pressure, irrespective of high cholesterol levels. Further exploration is necessary to clarify the involvement of TAFIs in the pathophysiology of primary hypertension, necessitating advanced investigatory initiatives.

References

  • 1. Aydoğdu A, Atlı T, Bayram F. Hipertansiyon Tanı Ve Tedavi Kılavuzu. Türkiye Endokrinoloji ve Metabolizma Derneği, 2022.
  • 2. Lip GY, Li-Saw-Hee FL. Does hypertension confer a hypercoagulable state? J Hypertens. 1998;16(7):913-916. doi: 10.1097/00004872-199816070-00003.
  • 3. Bajzar L, Nesheim M. The effect of activated protein C on fibrinolysis in cell-free plasma can be attributed specifically to attenuation of prothrombin activation. J Biol Chem. 1993;268(12):8608-8616.
  • 4. Bouma BN, Meijers JC. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). J Thromb Haemost. 2003;1(7):1566-1574. doi: 10.1046/j.1538-7836.2003.00329.x.
  • 5. van Hinsbergh VW, Bertina RM, van Wijngaarden A, van Tilburg NH, Emeis JJ, Haverkate F. Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium. Blood. 1985;65(2):444-451.
  • 6. Juhan-Vague I, Renucci JF, Grimaux M, et al. Thrombin-activatable fibrinolysis inhibitor antigen levels and cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2000;20(9):2156-2161. doi: 10.1161/01.atv.20.9.2156.
  • 7. Aso Y, Wakabayashi S, Yamamoto R, Matsutomo R, Takebayashi K, Inukai T. Metabolic syndrome accompanied by hypercholesterolemia is strongly associated with proinflammatory state and impairment of fibrinolysis in patients with type 2 diabetes: synergistic effects of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor. Diabetes Care. 2005;28(9):2211-2216. doi: 10.2337/diacare.28.9.2211.
  • 8. Santamaria A, Borrell M, Oliver A, et al. Association of functional thrombin-activatable fibrinolysis inhibitor (TAFI) with conventional cardiovascular risk factors and its correlation with other hemostatic factors in a Spanish population. Am J Hematol. 2004;76(4):348-352. doi: 10.1002/ajh.20108.
  • 9. Guven GS, Atalar E, Yavuz B, et al. Simvastatin treatment improves endothelial function and increases fibrinolysis in patients with hypercholestrolemia. J Natl Med Assoc. 2006;98(4):627-30.
  • 10. Williams B, Mancia G, Spiering W, et al; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104. doi: 10.1093/eurheartj/ehy339.
  • 11. Sean Kane, https://clincalc.com, recived 01.07.2020.
  • 12. Małyszko J, Tymcio J. Thrombin activatable fibrinolysis inhibitor and other hemostatic parameters in patients with essential arterial hypertension. Pol Arch Med Wewn. 2008;118(1-2):36-41.
  • 13. Sato T, Miwa T, Akatsu H, et al. Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not. J Immunol. 2000;165(2):1053-1058. doi: 10.4049/jimmunol.165.2.1053.
  • 14. Flick MJ, Du X, Witte DP, et al. Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo. J Clin Invest. 2004;113(11):1596-606. doi: 10.1172/JCI20741.
  • 15. Gil W. Inflammo-coagulatory response, extrinsic pathway thrombin generation and a new theory of activated clotting time interpretation. Perfusion. 2001;16(1):27-35. doi: 10.1177/026765910101600105.
  • 16. Małyszko J, Małyszko JS, Hryszko T, Myśliwiec M. Thrombin activatable fibrinolysis inhibitor (TAFI) and markers of endothelial cell injury in dialyzed patients with diabetic nephropathy. Thromb Haemost. 2004;91(3):480-486. doi: 10.1160/TH03-04-0243.
  • 17. Terekeci HM, Oktenli C, Ozgurtas T, et al. Increased asymmetric dimethylarginine levels in young men with familial Mediterranean fever (FMF): is it early evidence of interaction between inflammation and endothelial dysfunction in FMF? J Rheumatol. 2008;35(10):2024-2029.
  • 18. Malyszko J, Malyszko JS, Hryszko T, Mysliwiec M. Thrombin activatable fibrinolysis inhibitor in hypertensive kidney transplant recipients. Transplant Proc. 2006;38(1):105-107. doi: 10.1016/j.transproceed.2005.11.072.
  • 19. Ozkan G, Ulusoy S, Sönmez M, et al. Thrombin activatable fibrinolysis inhibitor (TAFI) levels in hypertensive patients and a comparison of the effects of amlodipine and ramipril on TAFI levels. Clin Exp Hypertens. 2013;35(2):134-140. doi: 10.3109/10641963.2012.702833.
  • 20. Santos IR, Fernandes AP, Carvalho MG, Sousa MO, Ferreira CN, Gomes KB. Thrombin-activatable fibrinolysis inhibitor (TAFI) levels and its polymorphism rs3742264 are associated with dyslipidemia in a cohort of Brazilian subjects. Clin Chim Acta. 2014;433:76-83. doi: 10.1016/j.cca.2014.02.030.
  • 21. Mosnier LO, von dem Borne PA, Meijers JC, Bouma BN. Plasma TAFI levels influence the clot lysis time in healthy individuals in the presence of an intact intrinsic pathway of coagulation. Thromb Haemost. 1998;80(5):829-835.
  • 22. Wada H, Nobori T, Watanabe R, Shiku H, Sakuragawa N. Plasma Levels of Plasminogen Activator Inhibitor-1 (PAI-1) and Thrombin Activatable Fibrinolysis Inhibitor (TAFI) in Patients with Disseminated Intravascular Coagulation (DIC). Turk J Haematol. 2002;19(2):235-7.
  • 23. Aso Y, Wakabayashi S, Yamamoto R, Matsutomo R, Takebayashi K, Inukai T. Metabolic syndrome accompanied by hypercholesterolemia is strongly associated with proinflammatory state and impairment of fibrinolysis in patients with type 2 diabetes: synergistic effects of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor. Diabetes Care. 2005;28(9):2211-2216. doi: 10.2337/diacare.28.9.2211.
  • 24. Santamaria A, Borrell M, Oliver A, et al. Association of functional thrombin-activatable fibrinolysis inhibitor (TAFI) with conventional cardiovascular risk factors and its correlation with other hemostatic factors in a Spanish population. Am J Hematol. 2004;76(4):348-352. doi: 10.1002/ajh.20108.
  • 25. Santamaria A, Martinez-Rubio A, Borrell M, Mateo J, Ortin R, Fontcuberta J. Risk of acute coronary artery disease associated with functional thrombin activatable fibrinolysis inhibitor plasma level. Haematologica. 2004;89(7):880-881.
  • 26. Lau HK, Segev A, Hegele RA, et al. Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of angiographic coronary restenosis. Thromb Haemost. 2003;90(6):1187-1191. doi: 10.1160/TH03-05-0308.
  • 27. Schroeder V, Chatterjee T, Mehta H, et al. Thrombin activatable fibrinolysis inhibitor (TAFI) levels in patients with coronary artery disease investigated by angiography. Thromb Haemost. 2002;88(6):1020-1025.
  • 28. Itoh T, Yoshimoto N, Hirano Y, Yamamoto K. Structural basis for the selective inhibition of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) by a selenium-containing inhibitor with chloro-aminopyridine as a basic group. Bioorg Med Chem Lett. 2018;28(13):2256-2260. doi: 10.1016/j.bmcl.2018.05.042.
  • 29. Yaoita N, Satoh K, Satoh T, et al. Thrombin-Activatable Fibrinolysis Inhibitor in Chronic Thromboembolic Pulmonary Hypertension. Arterioscler Thromb Vasc Biol. 2016;36(6):1293-1301. doi: 10.1161/ATVBAHA.115.306845.
  • 30. Wang X, Smith PL, Hsu MY, Tamasi JA, Bird E, Schumacher WA. Deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI) protected mice from ferric chloride-induced vena cava thrombosis. J Thromb Thrombolysis. 2007;23(1):41-49. doi: 10.1007/s11239-006-9009-4.
  • 31. Claesen K, Mertens JC, Leenaerts D, Hendriks D. Carboxypeptidase U (CPU, TAFIa, CPB2) in Thromboembolic Disease: What Do We Know Three Decades after Its Discovery? Int J Mol Sci. 2021;22(2):883. doi: 10.3390/ijms22020883.
  • 32. Beyazit Y, Sayilir A, Tanoglu A, et al. Plasma Thrombin-activatable Fibrinolysis Inhibitor Levels Correlate with the Disease Activity of Ulcerative Colitis. Intern Med. 2016;55(14):1831-1836. doi: 10.2169/internalmedicine.55.6473.
  • 33. Grosso G, Vikerfors A, Woodhams B, et al. Thrombin activatable fibrinolysis inhibitor (TAFI) - A possible link between coagulation and complement activation in the antiphospholipid syndrome (APS). Thromb Res. 2017;158:168-173. doi: 10.1016/j.thromres.2017.06.028.
  • 34. Park R, Song J, An SS. Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis. Korean J Hematol. 2010;45(4):264-268. doi: 10.5045/kjh.2010.45.4.264.
  • 35. Gorar S, Alioglu B, Ademoglu E, et al. Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus? J Lab Physicians. 2016;8(2):101-105. doi: 10.4103/0974-2727.180790.
  • 36. Radovanovic-Dinic B, Tesic-Rajkovic S, Ignjatovic A, Grgov S. Thrombin activatable fibrinolysis inhibitor as an indicator of the severity of acute pancreatitis. Turk J Gastroenterol. 2018;29(4):488-493. doi: 10.5152/tjg.2018.17666.
  • 37. Ma J, Cui L, Huo W, Wang G, Quan X, Zhang J. Correlation between Deep Venous Thrombosis and Inflammation in Patients after Implantation of Permanent Pacemaker. Iran J Public Health. 2020;49(1):30-36.
Year 2024, EARLY ONLINE, 1 - 10
https://doi.org/10.18621/eurj.1501230

Abstract

References

  • 1. Aydoğdu A, Atlı T, Bayram F. Hipertansiyon Tanı Ve Tedavi Kılavuzu. Türkiye Endokrinoloji ve Metabolizma Derneği, 2022.
  • 2. Lip GY, Li-Saw-Hee FL. Does hypertension confer a hypercoagulable state? J Hypertens. 1998;16(7):913-916. doi: 10.1097/00004872-199816070-00003.
  • 3. Bajzar L, Nesheim M. The effect of activated protein C on fibrinolysis in cell-free plasma can be attributed specifically to attenuation of prothrombin activation. J Biol Chem. 1993;268(12):8608-8616.
  • 4. Bouma BN, Meijers JC. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). J Thromb Haemost. 2003;1(7):1566-1574. doi: 10.1046/j.1538-7836.2003.00329.x.
  • 5. van Hinsbergh VW, Bertina RM, van Wijngaarden A, van Tilburg NH, Emeis JJ, Haverkate F. Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium. Blood. 1985;65(2):444-451.
  • 6. Juhan-Vague I, Renucci JF, Grimaux M, et al. Thrombin-activatable fibrinolysis inhibitor antigen levels and cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2000;20(9):2156-2161. doi: 10.1161/01.atv.20.9.2156.
  • 7. Aso Y, Wakabayashi S, Yamamoto R, Matsutomo R, Takebayashi K, Inukai T. Metabolic syndrome accompanied by hypercholesterolemia is strongly associated with proinflammatory state and impairment of fibrinolysis in patients with type 2 diabetes: synergistic effects of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor. Diabetes Care. 2005;28(9):2211-2216. doi: 10.2337/diacare.28.9.2211.
  • 8. Santamaria A, Borrell M, Oliver A, et al. Association of functional thrombin-activatable fibrinolysis inhibitor (TAFI) with conventional cardiovascular risk factors and its correlation with other hemostatic factors in a Spanish population. Am J Hematol. 2004;76(4):348-352. doi: 10.1002/ajh.20108.
  • 9. Guven GS, Atalar E, Yavuz B, et al. Simvastatin treatment improves endothelial function and increases fibrinolysis in patients with hypercholestrolemia. J Natl Med Assoc. 2006;98(4):627-30.
  • 10. Williams B, Mancia G, Spiering W, et al; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104. doi: 10.1093/eurheartj/ehy339.
  • 11. Sean Kane, https://clincalc.com, recived 01.07.2020.
  • 12. Małyszko J, Tymcio J. Thrombin activatable fibrinolysis inhibitor and other hemostatic parameters in patients with essential arterial hypertension. Pol Arch Med Wewn. 2008;118(1-2):36-41.
  • 13. Sato T, Miwa T, Akatsu H, et al. Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not. J Immunol. 2000;165(2):1053-1058. doi: 10.4049/jimmunol.165.2.1053.
  • 14. Flick MJ, Du X, Witte DP, et al. Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo. J Clin Invest. 2004;113(11):1596-606. doi: 10.1172/JCI20741.
  • 15. Gil W. Inflammo-coagulatory response, extrinsic pathway thrombin generation and a new theory of activated clotting time interpretation. Perfusion. 2001;16(1):27-35. doi: 10.1177/026765910101600105.
  • 16. Małyszko J, Małyszko JS, Hryszko T, Myśliwiec M. Thrombin activatable fibrinolysis inhibitor (TAFI) and markers of endothelial cell injury in dialyzed patients with diabetic nephropathy. Thromb Haemost. 2004;91(3):480-486. doi: 10.1160/TH03-04-0243.
  • 17. Terekeci HM, Oktenli C, Ozgurtas T, et al. Increased asymmetric dimethylarginine levels in young men with familial Mediterranean fever (FMF): is it early evidence of interaction between inflammation and endothelial dysfunction in FMF? J Rheumatol. 2008;35(10):2024-2029.
  • 18. Malyszko J, Malyszko JS, Hryszko T, Mysliwiec M. Thrombin activatable fibrinolysis inhibitor in hypertensive kidney transplant recipients. Transplant Proc. 2006;38(1):105-107. doi: 10.1016/j.transproceed.2005.11.072.
  • 19. Ozkan G, Ulusoy S, Sönmez M, et al. Thrombin activatable fibrinolysis inhibitor (TAFI) levels in hypertensive patients and a comparison of the effects of amlodipine and ramipril on TAFI levels. Clin Exp Hypertens. 2013;35(2):134-140. doi: 10.3109/10641963.2012.702833.
  • 20. Santos IR, Fernandes AP, Carvalho MG, Sousa MO, Ferreira CN, Gomes KB. Thrombin-activatable fibrinolysis inhibitor (TAFI) levels and its polymorphism rs3742264 are associated with dyslipidemia in a cohort of Brazilian subjects. Clin Chim Acta. 2014;433:76-83. doi: 10.1016/j.cca.2014.02.030.
  • 21. Mosnier LO, von dem Borne PA, Meijers JC, Bouma BN. Plasma TAFI levels influence the clot lysis time in healthy individuals in the presence of an intact intrinsic pathway of coagulation. Thromb Haemost. 1998;80(5):829-835.
  • 22. Wada H, Nobori T, Watanabe R, Shiku H, Sakuragawa N. Plasma Levels of Plasminogen Activator Inhibitor-1 (PAI-1) and Thrombin Activatable Fibrinolysis Inhibitor (TAFI) in Patients with Disseminated Intravascular Coagulation (DIC). Turk J Haematol. 2002;19(2):235-7.
  • 23. Aso Y, Wakabayashi S, Yamamoto R, Matsutomo R, Takebayashi K, Inukai T. Metabolic syndrome accompanied by hypercholesterolemia is strongly associated with proinflammatory state and impairment of fibrinolysis in patients with type 2 diabetes: synergistic effects of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor. Diabetes Care. 2005;28(9):2211-2216. doi: 10.2337/diacare.28.9.2211.
  • 24. Santamaria A, Borrell M, Oliver A, et al. Association of functional thrombin-activatable fibrinolysis inhibitor (TAFI) with conventional cardiovascular risk factors and its correlation with other hemostatic factors in a Spanish population. Am J Hematol. 2004;76(4):348-352. doi: 10.1002/ajh.20108.
  • 25. Santamaria A, Martinez-Rubio A, Borrell M, Mateo J, Ortin R, Fontcuberta J. Risk of acute coronary artery disease associated with functional thrombin activatable fibrinolysis inhibitor plasma level. Haematologica. 2004;89(7):880-881.
  • 26. Lau HK, Segev A, Hegele RA, et al. Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of angiographic coronary restenosis. Thromb Haemost. 2003;90(6):1187-1191. doi: 10.1160/TH03-05-0308.
  • 27. Schroeder V, Chatterjee T, Mehta H, et al. Thrombin activatable fibrinolysis inhibitor (TAFI) levels in patients with coronary artery disease investigated by angiography. Thromb Haemost. 2002;88(6):1020-1025.
  • 28. Itoh T, Yoshimoto N, Hirano Y, Yamamoto K. Structural basis for the selective inhibition of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) by a selenium-containing inhibitor with chloro-aminopyridine as a basic group. Bioorg Med Chem Lett. 2018;28(13):2256-2260. doi: 10.1016/j.bmcl.2018.05.042.
  • 29. Yaoita N, Satoh K, Satoh T, et al. Thrombin-Activatable Fibrinolysis Inhibitor in Chronic Thromboembolic Pulmonary Hypertension. Arterioscler Thromb Vasc Biol. 2016;36(6):1293-1301. doi: 10.1161/ATVBAHA.115.306845.
  • 30. Wang X, Smith PL, Hsu MY, Tamasi JA, Bird E, Schumacher WA. Deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI) protected mice from ferric chloride-induced vena cava thrombosis. J Thromb Thrombolysis. 2007;23(1):41-49. doi: 10.1007/s11239-006-9009-4.
  • 31. Claesen K, Mertens JC, Leenaerts D, Hendriks D. Carboxypeptidase U (CPU, TAFIa, CPB2) in Thromboembolic Disease: What Do We Know Three Decades after Its Discovery? Int J Mol Sci. 2021;22(2):883. doi: 10.3390/ijms22020883.
  • 32. Beyazit Y, Sayilir A, Tanoglu A, et al. Plasma Thrombin-activatable Fibrinolysis Inhibitor Levels Correlate with the Disease Activity of Ulcerative Colitis. Intern Med. 2016;55(14):1831-1836. doi: 10.2169/internalmedicine.55.6473.
  • 33. Grosso G, Vikerfors A, Woodhams B, et al. Thrombin activatable fibrinolysis inhibitor (TAFI) - A possible link between coagulation and complement activation in the antiphospholipid syndrome (APS). Thromb Res. 2017;158:168-173. doi: 10.1016/j.thromres.2017.06.028.
  • 34. Park R, Song J, An SS. Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis. Korean J Hematol. 2010;45(4):264-268. doi: 10.5045/kjh.2010.45.4.264.
  • 35. Gorar S, Alioglu B, Ademoglu E, et al. Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus? J Lab Physicians. 2016;8(2):101-105. doi: 10.4103/0974-2727.180790.
  • 36. Radovanovic-Dinic B, Tesic-Rajkovic S, Ignjatovic A, Grgov S. Thrombin activatable fibrinolysis inhibitor as an indicator of the severity of acute pancreatitis. Turk J Gastroenterol. 2018;29(4):488-493. doi: 10.5152/tjg.2018.17666.
  • 37. Ma J, Cui L, Huo W, Wang G, Quan X, Zhang J. Correlation between Deep Venous Thrombosis and Inflammation in Patients after Implantation of Permanent Pacemaker. Iran J Public Health. 2020;49(1):30-36.
There are 37 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases, Medical Biochemistry - Proteins, Peptides and Proteomics
Journal Section Original Articles
Authors

Ayla Yıldız 0000-0002-2982-9918

Kerem Okutur 0000-0002-8079-7739

Nezaket Eren 0000-0002-4078-1329

Early Pub Date August 21, 2024
Publication Date
Submission Date June 14, 2024
Acceptance Date August 11, 2024
Published in Issue Year 2024 EARLY ONLINE

Cite

AMA Yıldız A, Okutur K, Eren N. Assessment of thrombin-activatable fibrinolysis inhibitor levels in essential hypertension. Eur Res J. Published online August 1, 2024:1-10. doi:10.18621/eurj.1501230

e-ISSN: 2149-3189 


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