Thromb Haemost 2010; 104(04): 724-733
DOI: 10.1160/TH10-01-0048
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The effect of ethanol and its metabolism on fibrinolysis

Marlien Pieters
1   TReNDS Centre of Excellence – Nutrition, North-West University, Potchefstroom, South Africa
,
Hester H. Vorster
1   TReNDS Centre of Excellence – Nutrition, North-West University, Potchefstroom, South Africa
,
Johann C. Jerling
1   TReNDS Centre of Excellence – Nutrition, North-West University, Potchefstroom, South Africa
,
Christine S. Venter
1   TReNDS Centre of Excellence – Nutrition, North-West University, Potchefstroom, South Africa
,
Retha C. M. Kotze
1   TReNDS Centre of Excellence – Nutrition, North-West University, Potchefstroom, South Africa
,
Elsabe Bornman
2   School of Nursing Science, North-West University, Potchefstroom, South Africa
,
Joyce J. M. C. Malfliet
3   Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
,
Dingeman C. Rijken
3   Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
› Institutsangaben
Financial support:This study was supported by the National Research Foundation of South Africa.
Weitere Informationen

Publikationsverlauf

Received: 18. Januar 2010

Accepted after major revision: 24. Mai 2010

Publikationsdatum:
24. November 2017 (online)

Summary

The role of ethanol metabolism in possible haemostatic cardioprotective effects has not yet been determined. To this end, we investigated the effect of a moderate dose of ethanol (35 g) and its metabolism, on haemostatic variables over 14 hours (h). Eighteen Caucasian males participated in a placebo-controlled, randomised, cross-over study. Blood was collected prior to alcohol consumption, and at 10 time points for 14 h. Blood ethanol peaked at 1 h and was cleared after 8 h following ethanol consumption, significantly increasing plasma acetate (p=0.0028). Ethanol did not influence the coagulation factors significantly. PAI-1act increased (p<0.0001) and tPAact (p=0.047) decreased following alcohol consumption, reaching maximum (0.69 to 22.2 IU/ml) and minimum (0.88 to 0.33 IU/ml) levels at 5 h, respectively. Significantly increased plasma clot lysis times (46.8 to 67.6 minutes) and reduced global fibrinolytic capacity of whole blood, measured as D-dimer production during incubation of blood clots (2.26 to 0.29 μg/ml), were found at 5 h. Except for PAI-1act (borderline significance; p=0.05), there was no significant difference in the fibrinolytic markers between the two groups the following morning. Moderate ethanol consumption resulted in a significant temporary fibrinolysis inhibition. Any protective effects of moderate ethanol consumption on cardiovascular disease do not appear to be due to improvement in fibrinolytic potential within the first 14 h following consumption. The use of global fibrinolytic assays is recommended for determining the true effect of ethanol on fibrinolysis.

 
  • References

  • 1 Klatsky AL, Armstrong MA, Friedman GD. Risk of cardiovascular mortality in alcohol drinkers, ex-drinkers and nondrinkers. Am J Cardiol 1990; 66: 1237-1242.
  • 2 Lazarus NB, Kaplan GA, Cohen RD. et al. Change in alcohol consumption and risk of death from all causes and from ischaemic heart disease. Br Med J 1991; 303: 553-556.
  • 3 Rimm EB, Williams P, Fosher K. et al. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. Br Med J 1999; 319: 1523-1528.
  • 4 Mukamal KJ, Jadhav PP, D’Agostino RB. et al. Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort. Circulation 2001; 104: 1367-1373.
  • 5 Salem RO, Laposata M. Effects of alcohol on hemostasis. Am J Clin Pathol 2005; 123: S96-105.
  • 6 Biyik I, Ergene O. Alcohol and acute myocardial infarction. J Int Med Res 2007; 35: 46-51.
  • 7 Van de Wiel A, Van Golde PM, Kraaijenhagen RJ. et al. Acute inhibitory effect of alcohol on fibrinolysis. Eur J Clin Invest 2001; 31: 164-170.
  • 8 Van Golde PM, Hart HC, Kraaijenhagen RJ. et al. Regular alcohol intake and fibrinolysis. Neth J Med 2002; 60: 285-288.
  • 9 Hendriks HF, Veenstra J, Velthuis-te Wierik EJ. et al. Effect of moderate dose of alcohol with evening meal on fibrinolytic factors. Br Med J 1994; 308: 1003-1006.
  • 10 Paton A. Alcohol in the body. Br Med J 2005; 330: 85-87.
  • 11 Crouse JR, Gerson CD, DeCarli LM. et al. Role of acetate in the reduction of plasma free fatty acids produced by ethanol in man. J Lipid Res 1968; 9: 509-512.
  • 12 Siler SQ, Neese RA, Hellerstein MK. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am J Clin Nutr 1999; 70: 928-936.
  • 13 Weston AT, Petosa R, Pate RR. Validation of an instrument for measurement of physical activity in youth. Med Sci Sports Exerc 1997; 29: 138-143.
  • 14 Ainsworth BE, Haskell WL, Whitt MC. et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000; 32: S498-S504.
  • 15 Rijken DC, Hoegee-de Nobel E, Jie AF. et al. Development of a new test for the global fibrinolytic capacity in whole blood. J Thromb Haemost 2008; 6: 151-157.
  • 16 Lisman T, de Groot PG, Meijers JC. et al. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood 2005; 105: 1102-1105.
  • 17 Samarakoon R, Higgins PJ. Integration of non-SMAD and SMAD signaling in TGF-beta1-induced plasminogen activator inhibitor type-1 gene expression in vascular smooth muscle cells. Thromb Haemost 2008; 100: 976-983.
  • 18 Szabo G, Verma BK, Fogarasi M. et al. Induction of transforming growth factor-beta and prostaglandin E2 production by ethanol in human monocytes. J Leukoc Biol 1992; 52: 602-610.
  • 19 Van Golde PM, Kraaijenhagen RJ, Bouma BN. et al. No acute effect of red wine on the coagulation pathway in healthy men. Alcohol 2003; 29: 183-186.
  • 20 Rimm EB, Giovannucci EL, Willett WC. et al. Prospective study of alcohol consumption and risk of coronary disease in men. Lancet 1991; 338: 464-468.
  • 21 Wannamethee SG, Lowe GD, Shaper G. et al. The effects of different alcoholic drinks on lipids, insulin and haemostatic and inflammatory markers in older men. Thromb Haemost 2003; 90: 1080-1087.
  • 22 Veenstra J, Kluft C, Ockhuizen TH. et al. Effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator and plasminogen activator inhibitor. Thromb Haemost 1990; 63: 345-348.
  • 23 Numminen H, Syrjala M, Benthin G. et al. The effect of acute ingestion of a large dose of alcohol on the hemostatic system and its circadian variation. Stroke 2000; 31: 1269-1273.
  • 24 Sierksma A, Van der Gaag MS, Schaafsma G. et al. Moderate alcohol consumption and fibrinolytic factors of pre- and postmenopausal women. Nutrition Research 2001; 21: 171-181.
  • 25 Olsen H, Osterud B. Effects of ethanol on human blood fibrinolysis and coagulation. Alcohol 1987; 1: 591-594.
  • 26 Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost 2005; 93: 631-640.
  • 27 Szabo G, Mandrekar P, Girouard L. et al. Regulation of human monocyte functions by acute ethanol treatment: decreased tumor necrosis factor-alpha, interleukin-1 beta and elevated interleukin-10, and transforming growth factor-beta production. Alcohol Clin Exp Res 1996; 20: 900-907.
  • 28 Imhof A, Koenig W. Alcohol inflammation and coronary heart disease. Addict Biol 2003; 8: 271-277.
  • 29 Sawdey M, Podor TJ, Loskutoff DJ. Regulation of type 1 plasminogen activator inhibitor gene expression in cultured bovine aortic endothelial cells. Induction by transforming growth factor-beta, lipopolysaccharide, and tumor necrosis factor-alpha. J Biol Chem 1989; 264: 10396-10401.
  • 30 Juhan-Vague I, Pyke SD, Alessi MC. et al. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation 1996; 94: 2057-2063.
  • 31 Silveira A. Postprandial triglycerides and blood coagulation. Exp Clin Endocrinol Diabetes 2001; 109: S527-S532.
  • 32 Krebs M, Geiger M, Polak K. et al. Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man. Thromb Haemost 2003; 90: 422-428.
  • 33 Chen Y, Schneider DJ. The independence of signaling pathways mediating increased expression of plasminogen activator inhibitor type 1 in HepG2 cells exposed to free fatty acids or triglycerides. Int J Exp Diabetes Res 2002; 3: 109-118.
  • 34 Stiko-Rahm A, Wiman B, Hamsten A. et al. Secretion of plasminogen activator inhibitor-1 from cultured human umbilical vein endothelial cells is induced by very low density lipoprotein. Arteriosclerosis 1990; 10: 1067-1073.
  • 35 Eriksson P, Nilsson L, Karpe F. et al. Very-low-density lipoprotein response element in the promoter region of the human plasminogen activator inhibitor-1 gene implicated in the impaired fibrinolysis of hypertriglyceridemia. Arterioscler Thromb Vasc Biol 1998; 18: 20-26.