Download PDF
Thromb Haemost 1999; 82(S 01): 80-84
DOI: 10.1055/s-0037-1615560
Commentaries
Schattauer GmbH

Fibrinolytic Response to Venous Occlusion Compared to Physical Stress Test in Young Patients with Coronary Artery Disease

Mariam Nikfardjam
2   From the Departments of Cardiology
,
Senta Graf
2   From the Departments of Cardiology
,
Renate Beckmann
1   Vascular Biology and Thrombosis Research, University of Vienna, Austria
,
Stephan Hornykewycz
2   From the Departments of Cardiology
,
Jeanette Koller-Strametz
2   From the Departments of Cardiology
,
Bernd R. Binder
1   Vascular Biology and Thrombosis Research, University of Vienna, Austria
,
Kurt Huber
2   From the Departments of Cardiology
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2017 (online)

    Permissions and Reprints

Summary

Introduction: Venous occlusion (VO) and exercise stress (ES) are stimulators of the fibrinolytic system. Aim of this study was to answer which of both stimulation tests is more useful in patients with symptom-limited coronary artery disease (CAD) to evaluate possible defects in the fibrinolytic system.

Methods and results: We investigated 20 patients (M/F = 15/5; mean age = 36.7 years) with angiographically proven CAD for their plasma levels of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-type-1 (PAI-1) at basal conditions as well as after VO and at maximal ES (standardised bicycle stress test) and compared the data to those obtained from 12 sex- and age-matched healthy controls (M/F = 9/3; mean age = 40.4 years). At basal conditions mean t-PA activity and t-PA antigen plasma levels were within the normal range and comparable between the two study groups. After both VO and maximal ES, mean t-PA activity and t-PA antigen levels increased significantly more in the control group as compared to the CAD group. Mean PAI-1 activity plasma levels were significantly higher in the CAD group at basal conditions before VO (patients 7.0 ± 3.1; controls 3.9 ± 3.9; IU/ml; p = 0.025) as well as before ES (patients 8.1 ± 3.5; controls 4.3 ± 3.8; IU/ml; p = 0.009). PAI-1 activity plasma levels showed a significant decrease for patients and controls only after VO, while PAI-1 activity was not significantly decreased in both study groups at maximal ES.

Discussion: The significantly higher increase in mean plasma levels of t-PA activity and t-PA antigen after VO compared to ES in both groups might be explained by the fact that CAD induced symptoms in the patients during ES thus permitting only 80% of their age, sex, and body mass index related optimal work load.

Conclusion: VO and ES are applicable triggers of the endogenous fibrinolytic system in healthy subjects and patients who are not limited in their physical exercise. Standardised VO appears to be superior to ES as stimulation test of the endogenous fibrinolytic system in patients with symptomatic CAD.

Key words

Coronary artery disease - fibrinolytic system - venous occlusion - physical stress test
 

  • References

  • 1 Nilsson IM, Ljungner H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. British Medical Journal 1985; 290: 1453-5.
    CrossrefPubMedGoogle Scholar
  • 2 Sultan Y, Harris A, Strauch G, Venot A, De Lauture D. A dynamic test to investigate potential tissue plasminogen activator activity. Comparison of deamino-8-arginine vasopressin with venous occlusion in normal subjects and patients. Journal of Laboratory and Clinical Medicine 1988; 111: 645-53.
    PubMedGoogle Scholar
  • 3 Robertson BR, Pandolfi M, Nilsson IM. Fibrinolytic capacity in healthy volunteers at different ages as studied by standardized venous occlusion of arms and legs. Acta Medica Scandinavica 1972; 191: 199-202.
    PubMedGoogle Scholar
  • 4 Korninger C, Niessner H, Lechner K. Impaired fibrinolytic response to DDAVP and venous occlusion in a subgroup of patients with von Willebrand's disease. Thrombosis Research 1981; 23: 365-74.
    CrossrefPubMedGoogle Scholar
  • 5 Bauer J, Bachmann F. Fibrinolytic activity in healthy volunteers before and after 5 to 20 min of venous occlusion. Thrombosis Research 1984; 34: 159-74.
    CrossrefPubMedGoogle Scholar
  • 6 Keber D. Mechanism of tissue plasminogen activator release during venous occlusion. Fibrinolysis 1988; 2 (Suppl. 2) 96-103.
    PubMedGoogle Scholar
  • 7 Keber D, Blinc A, Fettich J. Increase of tissue plasminogen activator in limbs during venous occlusion: a simple haemodynamic model. Thromb Haemost 1990; 57: 67-72.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Wiman B, Mellbring G, Ranby M. Plasminogen activator release during venous stasis and exercise as determined by a new specific assay. Clin Chim Acta 1983; 127: 279-88.
    CrossrefPubMedGoogle Scholar
  • 9 Stegnar M, Pentek M. Fibrinolytic response to venous occlusion in healthy subjects: relationship to age, gender body weight blood lipids and insulin. Thromb Res 1993; 69: 81-92.
    CrossrefPubMedGoogle Scholar
  • 10 Szymanski LM, Pate RR, Durstine JL. Effects of maximal exercise and venous occlusion on fibrinolytic activity in physically active and inactive men. J Appl Physiol 1994; 77: 2305-10.
    CrossrefPubMedGoogle Scholar
  • 11 Lacroix KA, Bean C, Box L, Wagner K. A study of the fibrinolytic response in healthy men and women following a brief exposure to venous occlusion. Thromb Res 1996; 81: 133-43.
    CrossrefPubMedGoogle Scholar
  • 12 Chandler WL, Levy C, Stratton JR. The circulatory regulation of TPA and UPA secretion, clearance, and inhibition during exercise and during the infusion of isoproterenol and phenylephrine. Circulation 1995; 92: 2984-94.
    CrossrefPubMedGoogle Scholar
  • 13 Bourey RE, Santoro SA. Interactions of exercise, coagulation, platelets, and fibrinolysis - a brief review. Med Sci Sports Exerc 1988; 20: 439-46.
    PubMedGoogle Scholar
  • 14 Davis GL, Abilgaard CF, Bernauer EM, Britton M. Fibrinolytic and hemostatic changes during and after maximal exercise in males. J Appl Physiol 1976; 40: 287-92.
    CrossrefPubMedGoogle Scholar
  • 15 Rosing DR, Brakman P, Redwood DR. et al. Blood fibrinolytic activity in man. Diurnal variation and the response to varying intensities of exercise. Circ Res 1970; 27: 171-84.
    CrossrefPubMedGoogle Scholar
  • 16 Hansen J-B, Wilsgard L, Olsen JO, Osterud B. Formation and persistence of procoagulant and fibrinolytic activities in circulation after strenuous physical exercise. Thromb Haemost 1990; 64 (3) 385-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 van den, Burg PJM, Dooijewaard G, van Vliet M, Mosterd WL, Kluft C, Huisfeld IA. Differences in u-PA and t-PA increase during acute exercise: relation with exercise parameters. Thromb Haemost 1994; 71: 236-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Johansson L, Hedner U, Nilsson IM. A family with thromboembolic disease associated with deficient fibrinolytic activity in the vessel wall. Acta Med Scand 1978; 203: 477-80.
    PubMedGoogle Scholar
  • 19 Jorgensen M, Mortensen JZ, Madsen AG, Thorsen S, Jacobsen B. A family with reduced plasminogen activator activity in blood associated with recurrent venous thrombosis. Scandinavian Journal of Haematology 1982; 29: 217-23.
    PubMedGoogle Scholar
  • 20 Juhan-Vague J.V I, Alessi MC. et al. Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis. Thromb Haemost 1987; 57: 67-72.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Korninger C, Lechner K, Niessner H, Gossinger H, Kundi M. Impaired fibrinolytic capacity predisposes for recurrence of venous thrombosis. Thromb Haemost 1984; 52: 127-30.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Nguyen G, Horellou E.K.O.K MH, Conard J, Samama M. Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep vein thrombosis Blood 1988; 72: 601-5.
    PubMed
  • 23 Speiser W, Langer W, Pschaik A. et al. Increased blood fibrinolytic activity after physical exercise: comparative study in individuals with different sporting activities and in patients after myocardial infarction taking part in a rehabilitation sports program. Thromb Res 1988; 51: 543-55.
    CrossrefPubMedGoogle Scholar
  • 24 Huber K, Beckmann R, Graf A.G S, Probst P, Binder BR. Patients with recurrent restenosis after angioplasty exhibit a permanently decreased fibrinolytic potential. In: Gomez FP, Prentice C, Meyer J. ed. Coronary Thrombosis. Raven Press; 1993: 159-63.
    Google Scholar
  • 25 Baumgartner C, Huber K, Holzner F, Zeiler K, Auff E, Binder BR. Untersuchung zur Frage von persistierenden Veranderungen der Fibrinolyse-parameter t-PA und PAI bei Patienten nach juvenilem ischamischem cerebralem Insult. Klinische Wochenschrift 1988; 66: 1110-5.
    CrossrefPubMedGoogle Scholar
  • 26 Estelles A, Tormo G, Aznar J, Espana F, Tormo V. Reduced fibrinolytic activity in coronary heart disease in basal conditions and after exercise. Thrombosis Research 1985; 40: 373-83.
    CrossrefPubMedGoogle Scholar
  • 27 Rydzewski A, Sakata K, Kobayashi A. et al. Changes in plasminogen activator inhibitor 1 and tissue-type plasminogen activator during exercise in patients with coronary artery disease. Haemostasis 1990; 20: 305-12.
    PubMedGoogle Scholar
  • 28 Functional Functional and therapeutic classification of heart disease: functional capacity in angina. In: Clinical Cardiology. (5th ed). Sokolow M, Mcllroy MB, Cheitlin MD. eds. California: Appleton and Lange 1990: 44-5.
    Google Scholar
  • 29 Andreotti F, Davies GJ, Hackett DR. et al. Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death and stroke. American Journal of Cardiology 1988; 62: 635-7.
    CrossrefPubMedGoogle Scholar
  • 30 Angleton P, Chandler WL, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation 1989; 79: 101-6.
    CrossrefPubMedGoogle Scholar
  • 31 Huber K, Resch I, Rosc D, Schuster E, Glogar D, Binder BR. Circadian variation of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary artery disease and acute myocardial infarction. Thromb Haemost 1988; 60: 372-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Huber K, Beckmann R, Lang I, Schuster E, Binder BR. Circadian fluctuations in plasma levels of tissue plasminogen activator antigen and plasminogen activator inhibitor activity. Fibrinolysis 1989; 3: 41-3.
    PubMedGoogle Scholar
  • 33 Kluft C, Jie AFH, Rijken DC, Verheijen JH. Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast acting inhibitor (PAI-1). Thromb Haemost 1988; 59: 329-32.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Takada A, Takada Y, Urano T, Sakakibara K, Rydzewski A. Fluctuations of euglobulin lysis time, tissue plasminogen activator, and free and total plasminogen activator inhibitor levels in plasma in daytime. Thrombosis Research 1990; 57: 13-20.
    CrossrefPubMedGoogle Scholar
  • 35 Grimaudo V, Hauert J, Bachmann F, Kruithof EKO. Diurnal variation of the fibrinolytic system. Thromb Haemost 1988; 59: 495-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Wojta J, Turcu L, Wagner OF, Korninger C, Binder BR. Evaluation of fibrinolytic capacity by a combined assay system for t-PA antigen and t-PA function using monoclonal anti-t-PA antibodies. Journal of Laboratory and Clinical Medicine 1987; 109: 665-71.
    PubMedGoogle Scholar
  • 37 Wojta J, Holzer M, Hufnagl P, Christ G, Hoover R, Binder BR. Hyperthermia stimulates plasminogen activator inhibitor type 1 expression in human umbilical vein endothelial cells in vitro. Am J Pathol 1991; 139: 911-9.
    PubMedGoogle Scholar
  • 38 Keber D. On the use of different correction factors for haemoconcentration. Thromb Haemost. 1983 49. 245.
    PubMedGoogle Scholar
  • 39 Wieczorek I, Ludlam CA, MacGregor I. Venous occlusion does not release von Willebrand factor, factor VIII or PAI-1 from endothelial cells - the importance of consensus on the use of correction factors for hemoconcentration. Thromb Haemost 1993; 69: 91-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Held C, Hjemdahl P, Rehnqvist N, Wallen H, Bjorkander I, Eriksson SV, Forslund L, Wiman B. Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with Verapamil or Metoprolol. Circulation 1997; 95: 2380-6.
    CrossrefPubMedGoogle Scholar
  • 41 Keber D, Stegnar M, Kluft C. Different tissue plasminogen activator release in the arm and leg during venous occlusion is equalized after DDAVP infusion. Thromb Haemost 1990; 63: 72-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Stegnar M, Mavri A. Reproducibility of fibrinolytic response to venous occlusion in healthy subjects. Thromb Haemost 1995; 73: 453-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Lucore CL, Fry ETA, Nachowiak DA, Sobel BE. Biochemical determinants of clearance of tissue-type plasminogen activator from the circulation. Circulation 1988; 77: 906-14.
    CrossrefPubMedGoogle Scholar
  • 44 De Boer A, Kluft C, Kroon JM. et al. Liver blood flow as a major determinant of the clearance of recombinant human tissue-type plasminogen activator. Thromb Haemost 1992; 67: 83-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Huber K, Beckmann R, Probst P, Rauscha F, Kaindl F, Binder BR. Influence of cardiac output on peak t-PA plasma levels in patients receiving thrombolytic therapy with recombinant tissue-type plasminogen activator - correlation with patency rate. Thromb Haemost 1993; 69: 45-9.
    Article in Thieme ConnectPubMedGoogle Scholar