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Thromb Haemost 1988; 59(03): 495-499
DOI: 10.1055/s-0038-1647522
Original Article
Schattauer GmbH Stuttgart

Diurnal Variation of the Fibrinolytic System

V Grimaudo
1   The Laboratoire Central d’Hématologie, CHUV, Lausanne, Switzertand
,
J Hauert
1   The Laboratoire Central d’Hématologie, CHUV, Lausanne, Switzertand
,
F Bachmahh
1   The Laboratoire Central d’Hématologie, CHUV, Lausanne, Switzertand
,
E K O Kruithof
1   The Laboratoire Central d’Hématologie, CHUV, Lausanne, Switzertand
› Author Affiliations
Further Information

Publication History

Received 13 October 1987

Accepted after revision 19 February 1988

Publication Date:
29 June 2018 (online)

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Abstract

To elucidate which component(s) of thei fibrinolytic system is (are) responsible for the diurnal variation of fibrinolytic activity we have studied several parameters of this system in 8 healthy male volunteers during a period of. 24 h. Blood was collected at 8 a. m., 10 a. m., 12 a. m., 4 p.m., 8 p.m. and 8 a. m. next morning. The following tests were performed: euglobulin clot lysis time (ECLT), fibrinolytic activity of euglobulins on fibrin plates in the presence and absence of blocking antibodies to tissue-type plasminogen activator (t-PA) and/or urokinase (u-PA), overall plasminogen activator inhibitor (PAI) activity, antigen levels of t-PA, u-PA and PAI-I and zymography of the euglobulin fraction after SDS-PAGE. From 8-10 a. m. to 4-8 p. m., total fibrinolytic activity increased by 1l3% (p <0.01) or 71%h (p <0.01) when measured by ECIX or by fibrin plate assay, respectively. The immunoquenching experiments showed that this increase was entirely due to t-PA related activity whereas u-PA activity and t-PA/u-PA independent activity remained constant during the day. Average antigen levels of u-PA and t-PA in the afternoon were 6% and 25% lower than those measured in the morning. During this period, overall PAI activity and PAI-1 antigen decreased by 3l% (p <0.01) and 52% (p <0.01) respectively. Electrophoretic-zymographic analysis of_ the euglobulins revealed that throughout the day the majority of t-PA was present in the form of the 110 kDa t-PA/PAI-I complex. The intensity of this cornplex was lowest in the afternoon. Free t-PA was almost undetectable in morning samples, but constituted a significant proportion of total t-PA in the afternoon. The diurnal increase of fibrinolytic activity, therefore, is not due to an augmentation of antigen levels of t-PA and/or u-PA but to a decline of those of PAI-1.

Keywords

Diurnal - Fibrinolytic activity - PAI activity - t-PA - u-PA - PAI-1
 

  • References

  • 1 Rijken DC, Wijngaards G, Welbergen J. Relationship between tissue plasminogen activator and the activators in blood and vascular wall. Thromb Res 1980; 18: 815-30
    CrossrefPubMedSearch in Google Scholar
  • 2 Wun T-C, Schleuning W-D, Reich E. Isolation and characterization of urokinase from human plasma. J Biol Chem 1982; 257: 3276-3283
    PubMedSearch in Google Scholar
  • 3 Tissot J-D, Schneider P, Hauert J, Ruegg M, Kruithof EK O, Bachmann F. Isolation from human plasma of a plasminogen activator identical to urinary high molecular weight urokinase. J Clin Invest 1982; 70: 1320-1323
    CrossrefPubMedSearch in Google Scholar
  • 4 Wijngaards G, Kluft C, Groeneveld E. Demonstration of urokinase-related fibrinolytic activity in human plasma. Br J Haematol 1982; 51: 165-169
    CrossrefPubMedSearch in Google Scholar
  • 5 Kruithof EK O, Tran-Thang C, Ransijn A, Bachmann F. Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma. Blood 1984; 64: 907-913
    PubMedSearch in Google Scholar
  • 6 Verheijen JH, Chang GT G, Kluft C. Evidence for the occurrence of a fast-acting inhibitor for tissue-type plasminogen activator in human plasma. Thromb Haemostas 1984; 51: 392-395
    PubMedSearch in Google Scholar
  • 7 Chmielewska J, Rånby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thromb Res 1983; 31: 427-436
    CrossrefPubMedSearch in Google Scholar
  • 8 Fearnley GR, Balmforth G, Fearnley E. Evidence of a diurnal fibrinolytic rhythm; with a simple method of measuring natural fibrinolysis. Clin Sci 1957; 16: 645-650
    PubMedSearch in Google Scholar
  • 9 Kluft C, Verheijen JH, Rijken DC, Chang GT G, Jie AF H, Onkelinx C. Diurnal fluctuations in the activity of the fast-acting t-PA inhibitor. In: Progress in Fibrinolysis. Davidson JF, Donati MB, Coccheri S. Vol 7 Churchill Livingstone; Edinburgh: 1985: 117-119
    Search in Google Scholar
  • 10 Neerstrand H, Østergaard P, Bergquist D, Mätzsch T, Hedner U. tPA inhibitor, tPA:Ag, plasminogen, and α2-antiplasmin after low molecular weight heparin or standard heparin. Fibrinolysis 1987; 1: 39-43
    PubMedSearch in Google Scholar
  • 11 Kruithof EK O, Schleuning WD, Bachmann F. Human tissue-type plasminogen activator. Production in continuous serum-free cell culture and rapid purification. Biochem J 1985; 226: 631-636
    CrossrefPubMedSearch in Google Scholar
  • 12 Kruithof EK O, Nicoloso G, Bachmann F. Plasminogen activator inhibitor 1: Development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation. Blood 1987; 70: 1645-1653
    PubMedSearch in Google Scholar
  • 13 Kruithof EK O, Ransijn A, Bachmann F. Influence of detergents on the measurement of the fibrinolytic activity of plasminogen activators. Thromb Res 1982; 28: 251-260
    CrossrefPubMedSearch in Google Scholar
  • 14 Kruithof EK O, Tran-Thang C, Gudinchet A, Hauert J, Nicoloso G, Genton C, Welti H, Bachmann F. Fibrinolysis in pregnancy. a study of plasminogen activator inhibitors Blood 1987; 69: 460-466
    PubMedSearch in Google Scholar
  • 15 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
    CrossrefPubMedSearch in Google Scholar
  • 16 Granelli-Piperno A, Reich E. A study of proteases and proteaseinhibitor complexes in biological fluids. J Exp Med 1978; 148: 223-34
    CrossrefPubMedSearch in Google Scholar
  • 17 Langley R. Practical Statistics. Simply Explained. Dover Publications; New York: 1971
    Search in Google Scholar
  • 18 Kluft C. Studies on the fibrinolytic system in human plasma: quantitative determination of plasminogen activators and proactivators. Thromb Haemostas 1979; 41: 365-383
    PubMedSearch in Google Scholar
  • 19 Kluft C, Wijngaards G, Jie AF H. Intrinsic plasma fibrinolysis: involvement of urokinase-related activity in the factor Xll-independent plasminogen proactivator pathway. J Lab Clin Med 1984; 103: 408-419
    PubMedSearch in Google Scholar
  • 20 Hamsten A, Wiman B, de Faire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-1563
    CrossrefPubMedSearch in Google Scholar
  • 21 Hamsten A, Walldius G, Szamosi A, Blomback M, de Faire U, Dahlen G, Landou C, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3-9
    PubMedSearch in Google Scholar
  • 22 Toiler GH, Brezinski D, Schafer AI, Czeisler CA, Rutherford JD, Willich SN, Gleason RE, Williams GH, Muller JE. Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med 1987; 316: 1514-1518
    CrossrefPubMedSearch in Google Scholar
  • 23 Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, Kenneth Poole W, Passamani E, Roberts R, Robertson T, Sobel BE, Willerson JT, Braunwald E. The MILIS study group. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 1985; 313: 1315-1322
    CrossrefPubMedSearch in Google Scholar
  • 24 Muller JE, Ludmer PL, Willich SN, Tofler GH, Aylmer G, Klangos I, Stone PH. Circadian variation in the frequency of sudden cardiac death. Circulation 1987; 75: 131-138
    CrossrefPubMedSearch in Google Scholar