Thromb Haemost 1990; 64(01): 124-126
DOI: 10.1055/s-0038-1647267
Original Article
Schattauer GmbH Stuttgart

Physical Exercise Enhances Plasma Levels of Extrinsic Pathway Inhibitor (EPI)

John-Bjarne Hansen
The Institute of Medical Biology, University of Tromsø, Tromsø, Norway
,
Jan-Ole Olsen
The Institute of Medical Biology, University of Tromsø, Tromsø, Norway
,
Bjarne Østerud
The Institute of Medical Biology, University of Tromsø, Tromsø, Norway
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 20. Juli 1989

Accepted after revision 16. März 1990

Publikationsdatum:
25. Juli 2018 (online)

Summary

The risk of cardiovascular complications is reported to be several times higher in severe exercise than in daily activity. EPI-mediated inhibition of factor VTIa/thromboplastin enzymatic activity is believed to be an important modulator of blood coagulation during hemostasis. The plasma concentration of EPI, corrected for changes in plasma volume, was determined in healthy male subjects prior to, immediately after and at various time intervals after strenuous exercise of different duration. A slight, but significant decrease in EPI (7.5 ± 2.8%, p <0.03) was found after a short term run (1.7 km), whereas no significant change was seen after a middle term run (4.8 km). In contrast, we observed a marked increase in EPI after a long term run (20.3 ± 6.9%, p <0.03) and in a second group of athletes participating in the Norwegian championship of 30 km cross country skiing (39.9 ± 10.3%, p <0.02). A peak value was reached 2 h after the run, and after that the curve started to approach baseline values. The rise in EPI might reflect a significant release of EPI from the endothelium that is greater than eventually any consumption. Another explanation for this enhancement in EPI might be that the increase in lipoprotein lipase activity after physical exercise causes a rise in the availability of EPI since EPI is known to be associated with lipoproteins in the circulation.

It is hypothesized that mobilization of EPI during extensive physical exercise may suppress activation of the clotting system.

 
  • References

  • 1 Østerud B, Rapaport SI. Activation of factor IX by the reaction product of tissue factor and factor VII: Additional pathway for initiating blood coagulation. Proc Natl Acad Sci USA 1977; 74: 5260-5264
  • 2 Sanders NL, Bajaj SP, Zivelin A, Rapaport SI. Inhibition of tissue factor/factor Vila activity in plasma requires factor X and an additional plasma component. Blood 1985; 66: 204-212
  • 3 Broze Jr GJ, Miletich JP. Characterization of the inhibition of tissue factor in serum. Blood 1987; 69: 150-155
  • 4 Rao L VM, Rapaport SI. Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation. Blood 1987; 69: 645-651
  • 5 Broze Jr GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP. The lipoprotein-associated coagulation inhibitor that inhibits the factor VH-tissue factor complex also inhibits factor Xa: Insight into its possible mechanism of action. Blood 1988; 71: 335-343
  • 6 Broze Jr GJ, Miletich JP. Isolation of the tissue factor inhibitor produced by HepG2 hepatoma cells. Proc Natl Acad Sci USA 1987; 84: 1886-1890
  • 7 Bajaj MS, Rana SV, Wusolmerski RB, Bajaj SP. Inhibitor of the factor VH-tissue factor complex is reduced in patients with disseminated intravascular coagulation but not in patients with severe hepatocellular disease. J Clin Invest 1987; 79: 1874-1878
  • 8 Thompson PD, Funk EJ, Carleton RA, Sturner WG. Incidence of death during jogging in Rhode Island from 1975 through 1980. JAMA 1982; 247: 2535-2538
  • 9 Siscovick DS, Weiss NS, Fletcher RH. et al. The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 1984; 311: 874-877
  • 10 Rao L VM, Rapaport SI, Bajaj SP. Activation of human factor VII in the initiation of tissue factor dependent coagulation. Blood 1986; 68: 685-691
  • 11 Bourey RE, Santoro SA. Interactions of exercise, coagulation, platelets, and fibrinolysis – a brief review. Med Sci Sports Exerc 1988; 20: 439-446
  • 12 Van BeaumontW. Evaluation of hemoconcentration from hematocrit measurement. J Appl Physiol 1972; 32: 712-713
  • 13 Coreenleaf JE, Convertion VA, Mangseth GR. Plasma volume during stress in man: osmolality and red cell volume. J Appl Physiol 1979; 47: 1031-1038
  • 14 Hjort PF. Intermediate reaction in coagulation of blood with tissue thromboplastin. Scand J Lab Invest 1957; 9 (Suppl. 27) 183
  • 15 Sandset PM, Abildgaard U, Pettersen M. A sensitive assay of extrinsic coagulation pathway inhibitor (EPI) in plasma and plasma fractions. Thromb Res 1987; 47: 389-400
  • 16 Andersson TR, Bell H, Sandset PM, Ødegaard OR, Aamodt LM. “New” coagulation inhibitors levels in pneumonia, disseminated intravascular coagulation and liver diseases. Thromb Haemostas 1987; 58: 305 (Abstr)
  • 17 Sandset PM, Abildgaard U, Larsen ML. Heparin induces release of extrinsic coagulation pathway inhibitor (EPI). Thromb Res 1988; 50: 803-813
  • 18 Wam-Cramer BJ, Almus FE, Rapaport SI. Studies of the factor Xa dependent inhibitor of factor Vila/tissue factor (extrinsic pathway inhibitor) from cell supernates of cultured human umbilical vein endothelial cells. Thromb Haemostas 1989; 61: 101-105
  • 19 Warr TA, Rao L VM, Rapaport SI. Extrinsic pathway inhibitor in disseminated intravascular coagulation and severe acute and chronic liver disease. Circulation 1988; 7 (Supplement II) 255
  • 20 Peltonen P, Marniemi J, Hietanen E, Vuori I, Ehnholm C. Changes in serum lipids, lipoproteins, and heparin releasable lipolytic enzymes during moderate physical training in man: A longitudinal study. Metabolism 1981; 30: 518-526
  • 21 Weintraub MS, Rosen Y, Otto R, Eisenberg S, Breslow JL. Physical exercise conditioning in the absence of weight loss reduces fasting and postprandial triglyceride-rich lipoprotein levels. Circulation 1989; 79: 1007-1014
  • 22 Rapaport SI. Inhibition of factor Vila/tissue factor-induced blood coagulation: With particular emphasis upon a factor Xa dependent inhibitory mechanism. Blood 1989; 73: 359-365
  • 23 Berrettini M, Lammle B, Griffin JH. Initiation of coagulation and relationships between intrinsic and extrinsic coagulation pathway. In: Thrombosis and Haemostasis 1987 Verstraete M, Vermylen J, Lijnen R, Amout J. (eds) Leuven University Press; 1987: 473-495
  • 24 Østerud B, Olsen JO, Wilsgard L. Effect of strenuous exercise on blood monocytes and their relation to coagulation. Med Sci Sports Exerc 1989; 21: 374-378