Abstract
Purpose
The aim of this study was to examine coagulatory and fibrinolytic responses to the Western States Endurance Run (WSER, June 23 to 24, 2012). The WSER is a 161-km (100 mile) trail foot race through the Sierra Nevada Mountains that involves 6,030 m of climb and 7,001 m of descent.
Methods
We examined 12 men and 4 women [mean (95 % CI), age 44.6 years (38.7–50.6)] who completed the race (24.64 h; range 16.89–29.46). Blood samples were collected the morning before the race, immediately post-race, and 1 (D1) and 2 (D2) days post-race (corresponding to 51–54 h and 75–78 h from the start of the race, respectively). Hypercoagulable state was characterized by prothrombin fragment 1+2 (PTF 1+2) and thrombin–antithrombin complex (TAT). Fibrinolytic state was assessed by plasminogen activator inhibitor antigen (PAI-1 Ag), tissue plasminogen activator antigen (tPA Ag), and d-Dimer. Muscle damage was assessed by serum creatine kinase (CK) and myoglobin concentrations.
Results
Significant (P ≤ 0.05) increases were observed immediately post-race for thrombin generation markers, PTF 1+2 (3.9-fold) and TAT (2.4-fold); markers of fibrinolysis, tPA Ag (4.0-fold), PAI-1 Ag (4.5-fold), and d-Dimer (2.2-fold); and muscle damage markers, CK (154-fold) and myoglobin (114-fold). Most markers continued to be elevated at D1, as seen by PTF 1+2, TAT (1.5- and 1.3-fold increase at D1), and d-Dimer (2.5- and 2.1-fold increase at D1 and D2, respectively). Additionally, PTF 1+2:tPA and TAT:tPA ratios, which assessed balance between coagulation and fibrinolysis, were slightly, but significantly increased at D1 (69 and 36 %) and D2 (19 and 31 %). CK and myoglobin also remained elevated at D1 (54- and 7-fold) and D2 (25- and 2-fold) time points.
Conclusion
The WSER produced extensive muscle damage and activated the coagulation and fibrinolytic systems. Since we observed a slight imbalance response between the two systems, a limited potential for thrombotic episodes is apparent in these highly trained athletes.
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References
Angleton P, Chandler WL, Schmer G (1989) Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation 79:101–106
Arai M, Yorfuji H, Ikematsu S, Nagasawa H, Fujimaki M, Fukutake K, Katsumura T, Ishii T, Iwane H (1990) Influences of strenuous exercise (triathalon) on blood coagulation and fibrinolytic system. Thromb Res 57:465–471
Bartsch P, Haeberli A, Straub PW (1990) Blood coagulation after long distance running: antithrombin III prevents fibrin formation. 63:430–434
Brommer EJ, Barrett-Bergshoeff MM, Allen RA, Schicht I, Bertina RM, Schalekamp MA (1982) The use of desmopressin acetate (DDAVP) as a test of the fibrinolytic capacity of patients—analysis of responders and non-responders. Thromb Haemost 48:156–161
Bruso JR, Hoffman MD, Rogers IR, Lee L, Towle G, Hew-Butler T (2010) Rhabdomyolysis and hyponatremia: a cluster of five cases at the 161-km 2009 Western states endurance run. Wilderness Environ Med 21:303–308
Clarkson PM, Nosaka K, Braun B (1992) Muscle function after exercise-induced damage and rapid adaptation. Med Sci Sports Exerc 24:512–520
Hilberg T, Gläser D, Reckhart C, Prasa D, Stürzebecher J, Gabriel HH (2003) Blood coagulation and fibrinolysis after long-duration treadmill exercise controlled by individual anaerobic threshold. Eur J Appl Physiol 90:639–642
Hoffman MD, Ingwerson JL, Rogers IR, Hew-Butler T, Stuempfle KJ (2012) Increasing creatine kinase concentrations at 161-km Western States Endurance Run. Wilderness Environ Med 23:56–60
Hoffman MD, Stuempfle KJ, Fogard K, Hew-Butler T, Winger J (2013) Urine dipstick analysis for identification of runners susceptible to acute kidney injury following an ultramarathon. J Sports Sci 31:20–31
Levin EG, Marzec U, Anderson J, Harker (1984) Thrombin stimulates tissue plasminogen activator release from cultured human endothelial cells. J Clin Invest 74:1988–1995
Levin EG, Santell L, Saljooque F (1993) Hyperosmotic stress stimulates tissue plasminogen activator expression by a PKC-independent pathway. Am J Physiol 265:C387–C396
Lohman TG, Roche AF, Mortorell R (1988) Anthropometrics standardization reference manual, Human Kinetics Books. Champaign, IL 55–70
Mandalaki T, Dessypris A, Louizou C, Bossinakou I, Panayotopoulou C, Antonopoulou A (1977) Marathon run I: effects on blood coagulation and fibrinolysis. Thromb Haemost 37:444–450
Melamed I, Romem Y, Keren G, Epstein Y, Dolev E (1982) March myoglobinemia. a hazard to renal function. Arch Intern Med 142:1277–1279
Millet GY, Tomazin K, Verges S, Vincent C, Bonnefoy R, Boisson RC, Gergele L, Feasson L, Martin V (2011) Neuromuscular consequences of an extreme mountain ultra-marathon. PLoS One 6:e17059
Mockel M, Ulrich NV, Heller G Jr, Rocker L, Hansen R, Riess H, Patscheke H, Stork T, Ruf A (2001) Platelet activation through triathalon competition in ultra-endurance trained athletes: impact of thrombin and plasmin generation and catecholamine release. Int J Sports Med 22:337–343
Mydlik M, Derzsiova K, Bohus B (2012) Renal function abnormalities after marathon run and 16-kilometre long-distance run. Przegl Lek 69:1–4
Nieman DC, Dumke CL, Henson DA, McAnulty SR, Gross SJ, Lind RH (2005) Muscle damage is linked to cytokine changes following a 160-km race. Brain Behav Immun 19:398–403
Noakes TD (1987) Effect of exercise on serum enzyme activities in humans. Sports Med 4:245–267
Parker B, Augeri A, Capizzi J, Troyanos C, Kriz P, D’Hemecourt P, Thompson P (2011) Effect of air travel on exercise-induced coagulatory and fibrinolytic activation in marathon runners. Clin J Sport Med 21:126–130
Passaglia DG, Emed LG, Barberato SH, Guerios ST, Moser AI, Silva MM, Ishie E, Guarita-Souza LC, Costantini CR, Faria-Neto JR (2012) Acute effects of prolonged physical exercise: evaluation after a twenty-four-hour ultramarathon. Arq Bras Cardiol 100:21–28
Prisco D, Paniccia R, Guarnaccia V, Olivo G, Taddei T, Boddi M, Gensini GF (1993) Thrombin generation after physical exercise. Thromb Res 69:159–164
Prisco D, Paniccia R, Bandinelli B, Fedi S, Cellai AP, Liotta AA, Gatteschi L, Giusti B, Colella A, Abbate R, Gensini GF (1998) Evaluation of clotting and fibrinolytic activation after protracted physical exercise. Thromb Res 89:73–78
Rocker L, Drygas WK, Heyduck B (1986) Blood platelet activation and increase in thrombin activity following a marathon race. Eur J Appl Physiol 55:374–380
Rocker L, Taenzer M, Drygas WK, Lill H, Heyduck, Altenkirch HU (1990) Effect of prolonged physical exercise on the fibrinolytic system. Eur J Appl Physiol 60:478–481
Saenz AJ, Lee-Lewandrowski E, Wood MJ, Neilan TG, Siegel AJ, Januzzi JL, Lewandrowski KB (2006) Measurement of plasma stroke biomarker panel and cardiac troponin T in mmarathon runners before and after the 2005 Boston Marathon. Am J Clin Pathol 126:185–189
Schobersberger W, Wirleitner B, Puschendorf B, Koller A, Villiger B, Frey W, Mair J (1996) Influence of an ultramarathon race at moderate altitude on coagulation and fibrinolysis. Fibrinolysis 10:37–42
Siegel AJ, Stec JJ, Lipinska I, Van Cott EM, Lewandrowski KB, Ridker PM, Tofler GH (2001) Effect of marathon running on inflammatory and hemostatic markers. Am J Cardiol 88:918–920
Smith JE, Garbutt G, Lopes P, Tunstall Pedoe D (2004) Effects of prolonged strenuous exercise (marathon running) on biochemical and haematological markers used in the investigation of patients in the emergency department. Br J Sports Med 38:292–294
Staber WT, Clarkson PM, Fritz VK, Evans WJ (1990) Extracellular matrix disruption and pain after eccentric muscle action. J Appl Physiol 69:868–874
Stone MJ, Willerson JT, Gomez-Sanchez CE, Waterman MR (1975) Radioimmunoassay of myoglobin in human serum. Results in patients with acute myocardial infarction. J Clin Invest 1334-1339
Sumann G, Fries D, Griesmacher A, Falkensammer G, Klinger A, Koller A, Streif W, Greie S, Schobersberger B, Schobersberger W (2007) Blood coagulation and fibrinolysis downhill marathon run. Blood Coagul Fibrinol 18:435–440
Thompson PD, Funk EJ, Carleton RA, Sturner WQ (1982) Incedence of death during jogging in Rhode Island from 1975 through 1980. JAMA 247:2535–2538
Van Loon BJ, Heere LP, Kluft C, Briet E, Dooijewaard G, Meinders AE (1992) Fibrinolytic system during long-distance running in IDDM patients and in healthy subjects. Diabetes Care 15:991–996
Vilhardt H, Barth T (1991) The release of factor VIII and tissue plasminogen activator can not be blocked by specific antagonists to vasopressin. J Recept Res 11:239–245
Waskiewicz Z, Klapcinska B, Sadowska-Krepa E, Czuba M, Kempa K, Kimsa E, Gerasimuk D (2012) Acute metabolic responses to a 24-h ultra-marathon race in male amateur runners. Eur J Appl Physiol 112:1679–1688
Zager RA (1996) Rhabdomyolysis and myohaemoglobinuric acute renal failure. Kidney Int 49:314–326
Acknowledgments
The authors would like to thank the Western States Endurance Run Foundation for providing funds to support this research. The authors would also like to thank all of the test subjects for their participation in the study. In addition, we thank Peter Defty and Lauren Phinney for their help in subject recruitment and data collection.
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The authors declare that they have no conflict of interest.
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Communicated by Fabio Fischetti.
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Kupchak, B.R., Volk, B.M., Kunces, L.J. et al. Alterations in coagulatory and fibrinolytic systems following an ultra-marathon. Eur J Appl Physiol 113, 2705–2712 (2013). https://doi.org/10.1007/s00421-013-2709-5
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DOI: https://doi.org/10.1007/s00421-013-2709-5