Arterial and venous thromboembolic disorders remain the leading cause of death in most of the develop countries. A thrombotic occlusion of a coronary or cerebral artery, already damaged by atherosclerosis, appears to be a common and essential link in the onset of most of the cases of such vascular events and induces myocardial or cerebral infarctions [1, 2]. It is not surprising, therefore, that these vascular disorders and the hemostatic system are correlated. For example, high levels of plasma fibrinogen and factor VII coagulant activity were associated with an increased risk of death from cardiovascular disease [3]. High plasma levels of the fast-acting plasminogen activator inhibitor (PAI-1) seem also to be correlated with acute coronary thrombosis [4]. In venous thrombosis the relationship between the disease and the hemostatic system is even more patent. Thus, biological rhythms which modulate the hemostatic system are expected to relate to temporal changes in the incidence of thromboembolic disorders. Such rhythms may also induce temporal variations in the biological effect of antithrombotic agents. Possible therapeutic implications of these observations for the treatment of thromboembolic disorders deserve to be considered and evaluated.


Circadian Rhythm Deep Vein Thrombosis Sudden Cardiac Death Circadian Variation Morning Peak 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Davies MJ, Thomas AC (1984) Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med 310:1137–1140PubMedCrossRefGoogle Scholar
  2. 2.
    De Wood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT (1980) Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 303: 897–902CrossRefGoogle Scholar
  3. 3.
    Meade TW, Brozovic M Chakrabarti RR, Haines AP, Ime-son JD, Mellows S, Miller GJ, North WRS (1986) Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Study. Lancet 2: 533–537PubMedCrossRefGoogle Scholar
  4. 4.
    Hamsten A, Waldius G, Szamosi A (1987) Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 2: 3–9PubMedCrossRefGoogle Scholar
  5. 5.
    Cohen M, Simmons DJ, Joist JH (1978) Diurnal hemostatic changes in the rat. Thromb Res 12: 965–971PubMedCrossRefGoogle Scholar
  6. 6.
    Scheving LE, Pauly JE (1967) Daily rhythmic variations in blood coagulation times in rats. Anat Rec 157: 657–666PubMedCrossRefGoogle Scholar
  7. 7.
    Soulban G, Labrecque G (1989) Circadian rhythms of blood clotting time and coagulation factors II, VII, IX and X in rats. LifeSci 45:2485–2489CrossRefGoogle Scholar
  8. 8.
    Tofler GH, Brezinski D, Schafer Al, Czeiser CA, Rutherford JD, Willich SN, Glaeson RE, Williams GH, Muller JE (1987) Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med 316:1514–1518PubMedCrossRefGoogle Scholar
  9. 9.
    Brezinski D, Tofler GH, Muller JE (1988) Morning increase in platelet aggregability association with assumption of upright posture. Circulation 78: 35–40PubMedCrossRefGoogle Scholar
  10. 10.
    Mehta JL, Lawson D, Mehta P (1987) Circadian variation in platelet aggregation and alpha 2 adrenoceptor binding affinity. Circulation 76 (suppl IV): 364Google Scholar
  11. 11.
    Petralito A, Gibbino S, Maino MF (1982) Daily modification of plasma fibrinogen, platelet aggregation, Howell’s time, PTT, TT and antithrombin III in normal subjects and in patients with Valsalvar disease. Chronobiologia 9: 195–201PubMedGoogle Scholar
  12. 12.
    Weniger J, Panzram G (1985) Untersuchungen iiber das zirkadiane Verhalten hamostaseologischer Parameter bei Diabetikern und Stoffwechselgesunden. Z Gesamte Inn Med 40: 489–92PubMedGoogle Scholar
  13. 13.
    Willich SN, Pohjolva-Sintonen S, Bhatia SJS, Shook TL, Toiler GH, Muller JE, Curtis DG, Williams GH, Stone PH (1989) Suppression of silent ischemia by metoprolol without alteration of the morning increase of platelet aggregability in patients with stable coronary artery disease. Circulation 79: 557–565PubMedCrossRefGoogle Scholar
  14. 14.
    Haus E, Cusulos M, Sackett-Lundeen L, Swoyer J (1990) Circadian variations in platelet functions and coagulation parameters. Annu Rev Chronopharmacol 7:153–156Google Scholar
  15. 15.
    Conchonnet P, Decousus H, Boissier C, Perpoint B, Rey-naud J, Mismetti P, Tardy B, Queneau P (1990) Morning hypercoagulability in man. Annu Rev Chronopharmacol 7: 165–168Google Scholar
  16. 16.
    Fornasari P, Gratton L, Dolci D, Gamba G, Ascari E, Mon-talbetti N, Halberg F (1977) Circadian rhythms of clotting, fibrinolytic activators and inhibitors. In: Halberg F (ed) Proceedings of the XIII international conference of the International Society for Chronobiology. II Ponte, Milan, pp 155–158Google Scholar
  17. 17.
    Casale G, Butte M, Pasotti C, Ravecca D, de Nicola P (1983) Antithrombin III and circadian rhythms in the aged and in myocardial infarction. Haematologica 68: 615–619PubMedGoogle Scholar
  18. 18.
    Hajjar GC, Whissen NC, Moser K (1961) Diurnal variations in plasma euglobulin activity and fibrinogen levels. Angiology 12:160PubMedCrossRefGoogle Scholar
  19. 19.
    Porta M, Maneschi F, White MC, Kohner E (1981) Twenty-four hour variations of von Willebrand factor and factor VIII. Releated antigen in diabetic retinopathy. Metabolism 30: 695–699PubMedCrossRefGoogle Scholar
  20. 20.
    Toulon P, Vitoux JF, Leroy C, Lecomte TH, Roncato M, Motobashi Y, Aiach M, Fiessinger JN (1987) Circulating activities during constant infusion of heparin or a low molecular weight derivative (Enoxaparine): failure to demonstrate any circadian variations. Thromb Haemost 58:1068–1072PubMedGoogle Scholar
  21. 21.
    Sarji KE, Levine JH, Nair RMG, Sagel J, Colwell JA (1977) Relation between growth hormone levels and von Willebrand factor activity. J Clin Endocrinol Metab 45: 853PubMedCrossRefGoogle Scholar
  22. 22.
    Fearnley GR, Balmforth G, Fearnley E (1957) Evidence of a diurnal fibrinolytic rhythm with a simple method of measuring natural fibrinolysis. Clin Sci 16: 645PubMedGoogle Scholar
  23. 23.
    Buckell M, Elliott FA (1959) Diurnal fluctuation of plasma fibrinolytic activity in normal males. Lancet 1: 660PubMedCrossRefGoogle Scholar
  24. 24.
    Kowarzyk H, Kaniak J, Kotschym M (1960) Diurnal fluctuations of plasma fibrinolytic activity Lancet 1:176Google Scholar
  25. 25.
    Cepelak V, Barcal R, Celepakova H, Mayer O (1978) Circadian rhythm of fibrinolysis. In: Davidson JF et al. (eds) Progress in chemical fibrinolysis and thrombolysis, vol 3. Raven, New York, pp 571–578Google Scholar
  26. 26.
    Rosing DR, Brakman P, Redwood DR (1970) Blood fibrinolytic activity in man: diurnal variation and the response to varying intensities of exercise. Circ Res 27:171–184PubMedGoogle Scholar
  27. 27.
    Grimaudo V, Omri A, Kruithof EKO, Hauert J, Bachman F (1988) Fibrinolytic and anticoagulant activity after a single subcutaneous administration of a low dose of heparin or a low molecular weight heparin-dihydroergotamine combination. Thromb Haemost 59: 388–391PubMedGoogle Scholar
  28. 28.
    Grimaudo V, Hauert J, Bachmann F, Kruithof EKO (1988) Diurnal variation of the fibrinolytic system. Thromb Haemost 59: 495–499PubMedGoogle Scholar
  29. 29.
    Haglund O, Wibell L, Saldeen T (1985) Plasminogen activators and inhibitors in patients with deep venous thrombosis (DVT). Thromb Haemost 54: 271Google Scholar
  30. 30.
    Hafenberg J, Weber E, Spohr V, Mori H (1980) Is the diurnal increase in fibrinolytic activity influenced by alpha-adrenergic or beta-adrenergic blockade? Blut 41: 455–458CrossRefGoogle Scholar
  31. 31.
    Sprengers ED, Kluft C (1987) Plasminogen activator inhibitors. Blood 69: 381–387PubMedGoogle Scholar
  32. 32.
    Andreotti F, Davies GJ, Hackett D, Khan MI, de Bart A, Dooijewaard G, Maseri A, Kluft C (1988) Circadian variation of fibrinolytic factors in normal human plasma. Fibrinolysis 2 (suppl): 90–92Google Scholar
  33. 33.
    Kluft C, Jie AFH, Rijken DC, Verheijen JH (1988) Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast-acting inhibitor (PAI-1). Thromb Haemost 59: 329–332PubMedGoogle Scholar
  34. 34.
    Köhler M, Miyashita C (1988) Probleme bei der Messung von Parametern des fibrinolytischen Systems: circadiane Rhythmik von Gewebe-Plasminogen-Aktivator und Plas-minogen-Activator-Inhibitor. Klin Wochensch 66 (suppl XII): 62–67Google Scholar
  35. 35.
    Huber K, Beckmann R, Lang I, Schuster E, Binder BR (1989) Circadian fluctuations of plasma levels of tissue plasminogen activator antigen and plasminogen activator inhibitor activity. Fibrinolysis 3: 41–43CrossRefGoogle Scholar
  36. 36.
    Huber K, Resch I, Rose D (1987) Thrombotic complications in acute CAD can be correlated with elevated plasminogen activator inhibitor levels in plasma. Circulation 76 (suppl IV): IO/OGoogle Scholar
  37. 37.
    Angleton P, Chandler WL, Schmer G (1987) Diurnal variation in tissue plasminogen activator and its rapid inhibitor. Circulation 76 (suppl IV): 339Google Scholar
  38. 38.
    Seaman GVF, Engel R, Swank RL, Hissen W (1965) Circadian periodicity in some physicochemical parameters of circulating blood. Nature 4999: 833–835CrossRefGoogle Scholar
  39. 39.
    Ehrly AM, Jung G (1973) Circadian rhythm of human blood viscosity. Biorheology 10: 557–583Google Scholar
  40. 40.
    Bull GM, Brozonic M, Chakrabarti R, Meade TW, Horton J, North WRS, Stirling Y (1979) Relationship of air temperature to various chemical haematological and haemostatic variables. J Clin Pathol 32:16–20PubMedCrossRefGoogle Scholar
  41. 41.
    Keatinge WR, Coleshaw SRK, Cotter F, Mottoie M, Murphy M, Chelliah R (1984) Increases in platelet and red cell counts, blood viscosity and arterial pressure during mild surface cooling: factors in mortality from coronary and cerebral thrombosis in winter. Br Med J 289:1405–1408CrossRefGoogle Scholar
  42. 42.
    Churina SK, Ganelina JE, Volpert EL (1975) On the distribution of the incidence of acute myocardial infarction within a 24-hour period. Kardiologiia 15:115–119PubMedGoogle Scholar
  43. 43.
    Dimitrov L, Khadzhikhristev A (1983) Dynamics of the incidence of myocardial infarction in Smoljan District for the period 1965–1979. Vutr Boles 22: 40–46PubMedGoogle Scholar
  44. 44.
    Ganelina IE, Burisova IY (1983) Circadian rhythm of working capacity sympathicoadrenal activity, and myocardial infarction. Hum Physiol 9:113–120PubMedGoogle Scholar
  45. 45.
    Gyarfas I, Csukas A, Horath U, Gaudi I (1976) Analysis of the diurnal periodicity of acute myocardial infarction attacks. Sante Publique (Bucur) 19: 77–84Google Scholar
  46. 46.
    Johansson BW (1972) Myocardial infarction in Malmo (1960–1968). Acta Med Scand 191: 505–515PubMedGoogle Scholar
  47. 47.
    Kaufmann MW, Gottlieb G, Kahaner K (1981) Circadian rhythm and myocardial infarct: a preliminary study. IRCS J Med Sci 9: 557Google Scholar
  48. 48.
    Master AM (1960) The role of effort and occupation (including physicians) in coronary occlusion. JAMA 174: 942–948PubMedGoogle Scholar
  49. 49.
    Muller JE, Stone PH, Turi SG, Czeisler C (1985) Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 313:1315–1322PubMedCrossRefGoogle Scholar
  50. 50.
    Myers A, Dewar HA (1975) Circumstances attending 100 sudden deaths from coronary artery disease with coroner’s necropsies. Br Heart J 37:1133–1143PubMedCrossRefGoogle Scholar
  51. 51.
    WHO (1976) Myocardial infarction community registers. Results of a WHO international collaborative study coordinated by the regional office for Europe. In: Public Health in Europe, no 5, Copenhagen: Regional office for Europe (World Health Organization) 1976:1–232Google Scholar
  52. 52.
    Pedoe HT, Clayton D, Morris JN, Bridgen W, Mac Donald L (1975) Coronary heart attacks in East London. Lancet 2: 833–838PubMedCrossRefGoogle Scholar
  53. 53.
    Pell S, D’Alonzo CA (1963) Acute myocardial infarction in a large industrial population: report of a 6 years study of 1356 cases. JAMA 185: 831–838PubMedGoogle Scholar
  54. 54.
    Smolensky M (1983) Human chronopathology. In: Reinberg A, Smolensky M (eds) Biological rhythms and medicine: cellular, metabolic, physiopathologic and pharmacologic aspects. Springer, Berlin Heidelberg New York, p 209 (Topics in environmental physiology and medicine)Google Scholar
  55. 55.
    Thompson DR, Blandford RL, Sutton TW, Marchant PF (1985) Time of onset of chest pain in acute myocardial infarction. Int J Cardiol 7:1439–1467CrossRefGoogle Scholar
  56. 56.
    Willich SN, Linderer T, Wegscheider K, Leizorovicz A, Ala-mercery Y, Schroder R (1989) Increased morning incidence of myocardial infarction in the ISAM study: absence with prior beta-adrenergic blockade. Circulation 80: 853–858PubMedCrossRefGoogle Scholar
  57. 57.
    Muller JE, Ludmer PL, Willich SN, Toiler GH, Aylmer G, Klangos I, Stone PH (1987) Circadian variation in the frequency of sudden cardiac death. Circulation 75: 131–138PubMedCrossRefGoogle Scholar
  58. 58.
    Willich SN, Levy D, Rocco MB, Toiler GH, Stone PH, Mul- ler JE (1987) Circadian variation in the incidence of sudden cardiac death in the framingham heart study population. Am J Cardiol 60: 801–806PubMedCrossRefGoogle Scholar
  59. 59.
    Peters RW, Muller JE, Goldstein S, Byington R, Friedman LM (1989) Propanolol and the morning increase in the frequency of sudden cardiac death (BHAT study). Am J Cardiol 63:1518–1520PubMedCrossRefGoogle Scholar
  60. 60.
    Colantinio D, Casale R, Abruzzo B, Lorenzetti G, Pasqua-letti P (1989) Circadian distribution in fatal pulmonary thromboembolism. Am J Cardiol 64: 403–404CrossRefGoogle Scholar
  61. 61.
    Agnoli A, Manfredi M, Mossuto L, Piccinelli A (1975) Rapport entre les rythmes héméronyctaux de la tension artérielle et sa pathogénie de l’insuffisance vasculaire cérébrale. Rev Neurol (Paris) 131: 597–606Google Scholar
  62. 62.
    Marler JR, Price TR, Clark GL, Muller JE, Robertson T, Mohr JP, Hier DB, Wolf PA, Caplan LR, Foulkes MA (1989) Morning increase in onset of ischemic stroke. Stroke 20: 473–476PubMedCrossRefGoogle Scholar
  63. 63.
    Jovicic A (1983) Bioritam i shemieni cerebrovaskularni po-remecaji, Vojnosanit Pregl 40: 347–351PubMedGoogle Scholar
  64. 64.
    Tsementzis SA, Gill JS, Hitchcock ER (1985) Diurnal variation of and activity during the onset of stroke. Neurosurgery 17: 901–904PubMedCrossRefGoogle Scholar
  65. 65.
    Kaps M, Busse O, Hofmann O (1983) Zur circadianen Hau-figkeitsverteilung ischamischer Insulte. Nervenarzt 54: 655–657PubMedGoogle Scholar
  66. 66.
    Marshall J (1977) Diurnal variation of occurrence of strokes. Stroke 8: 230–231PubMedCrossRefGoogle Scholar
  67. 67.
    Hossmann V (1971) Circadian changes of blood pressure and stroke. In: Zulch KJ (ed) Cerebral circulation and stroke. Springer, Berlin Heidelberg New York, pp 203–208Google Scholar
  68. 68.
    Dewar HA, Weightman D (1983) A study of embolism in mitral valve disease and atrial fibrillation. Br Heart J 49: 133–140PubMedCrossRefGoogle Scholar
  69. 69.
    Muller JE, Tofler GH, Stone PH (1989) Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 79: 733–743PubMedCrossRefGoogle Scholar
  70. 70.
    Goldberg R, Brady P, Chen Z, Gore J, Flessas AK, Green-berg J, Thedosiou G, Dalen J, Muller JE (1989) Time of onset of acute myocardial infarction after awakening. J Am Coll Cardiol 13:133 AGoogle Scholar
  71. 71.
    Clark CV (1978) Seasonal variation in incidence of brachial and femoral emboli. Br Med J 287:1109CrossRefGoogle Scholar
  72. 72.
    Lawrence JC, Xabregas A, Gray L, Jam JL (1977) Seasonal variation in the incidence of deep vein thrombosis. Br J Surg 64: 777–780PubMedCrossRefGoogle Scholar
  73. 73.
    Reinberg A, Gervais P, Halberg F, Gauthier M (1973) Mortality des adultes: rythmes circadiens et circannuels dans un hopital parisien et en France. Presse Med 2: 289–294Google Scholar
  74. 74.
    Feinleib M (1972) Venous thrombosis in relation to cigarette smoking, physical activity and seasonal factors. Mil-bank Mem Fund Q 50 (suppl 2): 123–141CrossRefGoogle Scholar
  75. 75.
    Colantonio D, Casale R, Natali G, Pasqualetti P (1990) Seasonal periodicity in fatal pulmonary thromboembolism. Lancet 1: 56CrossRefGoogle Scholar
  76. 76.
    Wroblewski BM, Siney P, White R (1990) Seasonal variation in fatal pulmonary embolism after hip arthroplasty. Lancet 1:56–57CrossRefGoogle Scholar
  77. 77.
    Decousus H, Croze M, Levi F, Perpoint B, Jaubert J, Bona-dona JF, Reinberg A, Queneau P (1985) Circadian changes in anticoagulant effect of heparin infused at a constant rate. Br Med J 290: 341–344CrossRefGoogle Scholar
  78. 78.
    Decousus H, Scully MF, Reynaud J (1987) Circadian changes in anticoagulant effect of heparin given by subcutaneous bolus. Thromb Haemost 58:1376Google Scholar
  79. 79.
    Schved JF, Gris JC, Eledjam J J (1985) Circadian changes in anticoagulant effect of heparin infused at a constant rate. Br Med J 290:1286CrossRefGoogle Scholar
  80. 80.
    Fagrell B, Arver S, Intaglietta M, Tsai AG (1989) Changes of activated partial thromboplastin time during constant intravenous and fixed intermittent subcutaneous administration of heparin. J Int Med 225:257–260CrossRefGoogle Scholar
  81. 81.
    Kher A, Bara L, Samama M (1986) Les héparines de bas poids moléculaire. Pathol Biol 34: 61–69PubMedGoogle Scholar
  82. 82.
    Docousus M, Gremillet E, Decousus H, Champailler A, Housard D, Perpoint B, Jaubert J (1985) Nycthemeral variations of 99 Tc-labelled heparin-pharmacokinetic parameters. Nucl Med Commun 6: 633–640CrossRefGoogle Scholar
  83. 83.
    Scully MF, Decousus H, Ellis C, Girard P, Parker C, Kakkar VV (1987) Measurement of heparin in plasma: influence of inter-subject and circadian variability in heparin sensitivity according to method. Thromb Res 46: 447–455PubMedCrossRefGoogle Scholar
  84. 84.
    Becker RC, Carrao JM, Baker SP, Gore JM, Alpert JS (1988) Circadian variation in thrombolytic response to recombinant tissue-type plasminogen activator in acute myocardial infarction. J Appl Cardiol 3: 213–221Google Scholar
  85. 85.
    Moore JG, Goo H (1987) Day and night aspirin induced gastric mucosal damage and protection by ranitidine in man. Chronobiol Int 4:111–116PubMedCrossRefGoogle Scholar
  86. 86.
    Levi F, Le Louarn G, Reinberg A (1985) Timing optimizes sustained-release indomethacin treatment of osteoarthritis. Clin Pharmacol Ther 37: 77–84PubMedCrossRefGoogle Scholar
  87. 87.
    Boissier C, Decousus H, Perpoint B, Laporte S, Mismetti P, Hocquart J, Gayet JL, Queneau P (1990) Timing optimizes sustained-release ketoprofen treatment of osteoarthritis. Annu Rev Chronopharmacol 7: 289–292Google Scholar
  88. 88.
    Clench J, Reinberg A, Dziewanowska Z, Ghata J, Smolensky MH (1981) Circadian changes in the bioavailability and effects of indomethacin in healthy subjects. Eur J Clin Pharmacol 20: 359–369PubMedCrossRefGoogle Scholar
  89. 89.
    Ollagnier M, Decousus H, Cherrah Y, Levi F, Mechkouri M, Queneau P, Reinberg A (1987) Circadian changes in the pharmacokinetics of oral ketoprofen. Clin Pharmacokinet 12: 367–378PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • H. Decousus

There are no affiliations available

Personalised recommendations