The Basis for the Increase in Factor VIII Procoagulant Activity During Exercise

Summary

We studied the effect of acute exercise on the ability of thrombin to activate plasma factor VIII (FVIII) activity in 20 healthy males. The subject showed an average exercise-related increase in FVIII activity of 54.5±8.2% over pre-exercise FVIII activity (p<0.001). When exposed to the same concentration of thrombin, post-exercise FVIII activity showed greater enhancement than pre-exercise FVIII activity: 157.1±12.8% increase in activity versus 117.3±9.9%, respectively (p<0.01). The degree of the potentiated thrombin effect in post-exercise samples relative to pre-exercise samples was linearly correlated with the degree of the exercise-related increase in FVIII activity. Taken together with our previous observations that the extent of thrombin enhancement of FVIII activity varies inversely with the mole ratio of FVIII/von Willebrand factor subunits to thrombin, these findings imply that release of FVIII does not occur during exercise, and that the exercise-related increase in FVIII activity results primarily, if not completely, from activation of already circulating but inactive FVIII.

Keywords

FVIII/vWF - Factor VIII/von Willebrand factor - Exercise and factor VIII activity increase - Thrombin and factor VIII

• References

• 1 Legaz ME, Schmer G, Counts RB, Davie EW. Isolation and characterization of human factor VIII (antihemophilic factor). J Biol Chem 1973; 248: 3946-3955
• 2 Shapiro GA, Andersen JC, Pizzo SV, McKee PA. The subunit structure of normal and hemophilic factor VIII. J Clin Invest 1973; 52: 2198-2210
• 3 Hultin MB, Nemerson Y. Activation of factor X by factors IX_a, and VIII; A specific assay for factor IX_a, in the presence of thrombin-activated factor VIII. Blood 1978; 52: 928-940
• 4 Hoyer LW, Trabold NC. The effect of thrombin on human factor VIII. Cleavage of the factor VIII procoagulant protein during activation. J Lab Clin Med 1981; 97: 50-64
• 5 Kopitsky RG, Switzer ME P, McKee PA. Thrombin potentiation of factor VIII procoagulant activity: Assessment by the two-stage assay. Thromb Haemostas 1982; 47: 145-149
• 6 Vehar GA, Davie EW. Preparation and properties of bovine factor VIII (antihemophilic factor). Biochemistry 1980; 19: 401-410
• 7 Rapaport SI, Schiffman S, Patch MI, Ames SB. The importance of activation of antihemophilic globulin and proaccelerin by traces of thrombin in the generation of intrinsic prothrombinase activity. Blood 1963; 21: 221-235
• 8 Hultin MB. Role of human factor Vtn in factor X activation. J Clin Invest 1982; 69: 950-958
• 9 Switzer ME P, Pizzo SV, McKee PA. Is there a precursive, relatively procoagulant-inactive form of normal antihemophilic factor (factor VIII)?. Blood 1979; 54: 916-927
• 10 van DieijenG, Tans G, Rosing J, Hemker HC. The role of phospholipid and factor VIIIa in the activation of bovine factor X. J Biol Chem 1981; 256: 3433-3442
• 11 Bennett B, Ratnoff OD. Changes in antihemophilic factor (AHF, factor VIII) procoagulant activity and AHF-like antigen in normal pregnancy, and following exercise and pneumoencephalography. J Lab Clin Med 1972; 80: 256-263
• 12 Cooperberg AA, Teitelbaum JI. The concentration of antihemophilic globulin (AHG) in patients with coronary artery disease. Ann Intern Med 1961; 54: 899-907
• 13 Kendall AG, Lohmann RC, Dossetor JB. Nephrotic syndrome. A hypercoagulable state. Arch Intern Med 1971; 127: 1021-1027
• 14 Sarji KE, Eurenius K, Fullwood CO, Schraibman HB, Colwell JA. Abnormalities of platelet aggregation in sickle cell anemia. Presence of a plasma factor inhibiting aggregation by ristocetin. Thromb Res 1979; 14: 283-297
• 15 Rizza CR, Eipe I. Exercise, factor VIII and the spleen. Br J Haematol 1971; 20: 629-635
• 16 Cohen RJ, Epstein SE, Cohen LS, Dennis LH. Alterations of fibrinolysis and blood coagulation induced by exercise, and the role of betaadrenergic receptor stimulation. Lancet 1968; 02: 1264-1266
• 17 Prentice CR M, Forbes CD, Smith SM. Rise of factor VIII after exercise and adrenaline infusion, measured by immunological and biological techniques. Thromb Res 1972; 01: 493-506
• 18 Gastel Cvan, Sixma JJ, Borst-Eilers E, Leautand M, Moes M, Plas PM van der, Bouma BN, Sybesma Ph J. Preparation and infusion of cryoprecipitate from exercised donors. Br J Haematol 1973; 25: 461-466
• 19 Davis GL, Abildgaard CF, Bemauer EM, Britton M. Fibrinolytic and hemostatic changes during and after maximal exercise in males. J Appl Physiol 1976; 40: 287-292
• 20 Stibbe J. Effect of exercise on FVIII-complex: Proportional increase of ristocetin cofactor (von Willebrand factor) and FVIII-AGN, but disproportional increase of FVIII-AHF. Thromb Res 1977; 10: 163-168
• 21 Brown JE, Baugh RF, Hougie C. Effect of exercise on the factor VIII complex: A correlation of the von Willebrand antigen and factor VIII coagulant antigen increase. Thromb Res 1979; 15: 61-67
• 22 Switzer ME P, McKee PA. Reactions of thrombin and human factor VIII/von Willebrand factor protein. J Biol Chem 1980; 255: 10606-10611
• 23 Balke B, Ware RW. An experimental study of “physical fitness” of Air Force personnel. US Armed Forces Med J 1959; 10: 675-688
• 24 Langdell RD, Wagner RH, Brinkhous KM. Effect of antihemophilic factor on one-stage clotting tests. J Lab Clin Med 1953; 41: 637-647
• 25 Reisner HM, Barrow ES, Graham JB. Radioimmunoassay for coagulant factor VIII-related antigen (VIII: CAg). Thromb Res 1979; 14: 235-239