Thrombin Potential and Thrombin Generation After Exhaustive Exercise

Abstract

Exhaustive exercise leads to an activation of blood coagulation, but the implications of this activation are still unclear. The aim of this study was to investigate if a hypercoagulant stage exists after exhaustive treadmill- or cycle exercise; intrinsic and extrinsic endogenous thrombin potential (ETP) were measured by using the method of Hemker et al. [10]. Thirteen healthy male subjects underwent an exhaustive treadmill (TR) or cycle (CY) ergometer test and a control-day in random order. Blood samples were taken, repeatedly, after a 30 min rest, immediately before and after, and 1 h after exercise for measuring intrinsic and extrinsic total thrombin potential (TTPin, TTPex) (including free and α₂-macroglobulin-bound thrombin) and endogenous thrombin potential (ETPin, ETPex), aPTT, PT, F1 + 2 and TAT. In comparison to the pre-value taken immediately before the exercise, the intrinsic TTP was significantly (p < 0.05) increased directly after exercise (TR-TTPin, + 11.6 %; CY-TTPin, + 11.5 %). In contrast, ETPin remained unchanged after both exercises. Additionally for TTPex and ETPex, no changes after exercise were detectable. aPTT was significantly (p < 0.05) shorter after exercise (TR-aPTT, - 16.2 %; CY-aPTT - 17.5 %), F1 + 2-concentrations were higher (p < 0.05) (TR-F1 + 2, + 21.2 %; CY-F1 + 2, + 9.8 %), but TAT remained unchanged. Differences between TR or CY could not be determined. These results show the expected shortening of aPTT and the increase of F1 + 2 indicating an activation of the coagulation system during exercise. However, the unchanged intrinsic and extrinsic ETP lead to the conclusion that in healthy young male subjects the potential for thrombin generation is insignificant, is directly counterbalanced by α₂-macroglobulin and is independent of the type of exhaustive exercise done.

aPTT - F1 + 2 - TAT - blood coagulation - hypercoagulability - physical activity

References

• 1 Arai M, Yorifuji H, Ikematsu S, Nagasawa H, Fujimaki M, Fukutake K, Katsumura T, Ishii T, Iwane H. Influences of strenuous exercise (triathlon) on blood coagulation and fibrinolytic system.  Thromb Res. 1990;  57 465-471
• 2 Bärtsch P, Haeberli A, Straub P W. Blood coagulation after long distance running: antithrombin III prevents fibrin formation.  Thromb Haemost. 1990;  63 430-434
• 3 Bärtsch P, Welsch B, Albert M, Friedmann B, Levi M, Kruithof E K. Balanced activation of coagulation and fibrinolysis after a 2-h triathlon.  Med Sci Sports Exerc. 1995;  27 1465-1470
• 4 Dill D B, Costill D L. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration.  J Appl Physiol. 1974;  37 247-248
• 5 Dufaux B, Order U, Liesen H. Effect of a short maximal physical exercise on coagulation, fibrinolysis, and complement system.  Int J Sports Med. 1991;  12 S38-S42
• 6 Ferguson E W, Bernier L L, Banta G R, Yu-Yahiro J, Schoomaker E B. Effects of exercise and conditioning on clotting and fibrinolytic activity in men.  J Appl Physiol. 1987;  62 1416-1421
• 7 Foti A, Kimura S, DeQuattro V, Lee D. Liquid-chromatographic measurement of catecholamines and metabolites in plasma and urine.  Clin Chem. 1987;  33 2209-2213
• 8 Herren T, Bärtsch P, Haeberli A, Straub P W. Increased thrombin-antithrombin III complexes after 1 h of physical exercise.  J Appl Physiol. 1992;  73 2499-2504
• 9 Hemker H C, Beguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential.  Thromb Haemost. 1995;  74 134-138
• 10 Hemker H C, Wielders S, Kessels H, Beguin S. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential.  Thromb Haemost. 1993;  70 617-624
• 11 Hilberg T, Jeschke D, Gabriel H HW. Hereditary thrombophilia in elite athletes.  Med Sci Sports Exerc. 2002;  34 218-221
• 12 Hilberg T, Nowacki P E, Müller-Berghaus G, Gabriel H HW. Changes in blood coagulation and fibrinolysis associated with maximal exercise and physical conditioning in women taking low dose oral contraceptives.  J Sci Med Sport. 2000;  3 383-390
• 13 Prasa D, Svendsen L, Stürzebecher J. The ability of thrombin inhibitors to reduce the thrombin activity generated in plasma on extrinsic and intrinsic activation.  Thromb Haemost. 1997;  77 498-503
• 14 Prasa D, Svendsen L, Stürzebecher J. Inhibition of thrombin generation in plasma by inhibitors of factor Xa.  Thromb Haemost. 1997;  78 1215-1220
• 15 Prisco D, Paniccia R, Bandinelli B, Fedi S, Cellai A P, Liotta A A, Gatteschi L, Giusti B, Colella A, Abbate R, Gensini G F. Evaluation of clotting and fibrinolytic activation after protracted physical exercise.  Thromb Res. 1998;  89 73-78
• 16 Rocker L, Mockel M, Westpfahl K P, Gunga H C. Influence of maximal ergometric exercise on endothelin concentrations in relation to molecular markers of the hemostatic system.  Thromb Haemost. 1996;  75 12-616
• 17 Rotteveel R C, Roozendaal K J, Eijsman L, Hemker H C. The influence of oral contraceptives on the time-integral of thrombin generation (thrombin potential).  Thromb Haemost. 1993;  70 959-962
• 18 Stegmann H, Kindermann W, Schnabel A. Lactate kinetics and individual anaerobic threshold.  Int J Sports Med. 1981;  2 160-165
• 19 Weiss C, Seitel G, Bärtsch P. Coagulation and fibrinolysis after moderate and very heavy exercise in healthy male subjects.  Med Sci Sports Exerc. 1998;  30 246-251
• 20 Weiss C, Welsch B, Albert M, Friedmann B, Strobel G, Jost J, Nawroth P, Bärtsch P. Coagulation and thrombomodulin in response to exercise of different type and duration.  Med Sci Sports Exerc. 1998;  30 1205-1210
• 21 Wielders S, Mukherjee M, Michiels J, Rijkers D TS, Cambus J P, Knebel R WC, Kakkar V, Hemker H C, Beguin S. The routine determination of the endogenous thrombin potential, first results in different forms of hyper- and hypocoagulability.  Thromb Haemost. 1997;  77 629-636
• 22 Wu K K, Matijevic-Aleksic N. Thrombmodulin: a linker of coagulation and fibrinolysis and predictor of risk of arterial thrombosis.  Ann Med. 2000;  32 73-77