The Effects of Bedrest on Circadian Changes in Hemostasis

 

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Summary

Venous stasis occurs when people are at bedrest, because of altered venous flow characteristics. This is commonly believed to be one etiology behind the development of deep venous thrombosis (DVT). The hemostatic effects of bedrest and their possible role in DVT development have not been fully examined. We hypothesized that bedrest would lead to increases in hemostatic function and that these increases could be important in the development of DVT.

Twelve non-smoking volunteers were studied during supine positioning for 36 hours. Platelet reactivity and plasma concentrations of fibrinogen, a2-antiplasmin, plasminogen, thromboxane (32, plasminogen activator inhibitor-1, tissue plasminogen activator and neuroendocrine hormones (cortisol, epinephrine and norepinephrine) were measured at 8:00 a.m., 10:00 a.m., 4:00 p.m. and 8:00 a.m.

Cortisol demonstrated an early morning increase while catecholamines were unchanged throughout. Fibrinogen, a2-antiplasmin, plasminogen and platelet reactivity were no different at any time point. Fibrinolytic proteins changed over time, manifested by decreased PAI-1 antigen and activity levels at 24 h.

Based upon the parameters measured, bedrest causes no increase in hemostatic function. In fact, bedrest causes the potential for enhanced fibrinolysis, that differs from that previously reported for normal activity over 24 h. This may represent a protective mechanism to counter the effects of stasis from bedrest.

• References

• 1 Ehrly AM, Jung G. Circadian rhythm of human blood viscosity. Biorheolo-gy 1973; 10: 577-583
  CrossrefPubMedGoogle Scholar
• 2 Tofler GH, Brezinski DA, Schafer AI, Czeisler AC, Rutherford JD, Willich SN, Gleason RA, Williams HG, 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
  CrossrefPubMedGoogle Scholar
• 3 Angleton P, Chandler WL, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation 1989; 79: 101-106
  CrossrefPubMedGoogle Scholar
• 4 Brezinski DA, Tofler GH, Muller JE, Pohjola-Sintonen S, Willich SN, Schafer AI, Czeisler CA, Williams GH. Morning increase in platelet aggregability. Association with assumption of the upright posture. Circulation 1988; 78: 35-40
  CrossrefPubMedGoogle Scholar
• 5 Grimaudo V, Hauer J, Bachmann F, Kruithof EKO. Diurnal variation of the fibrinolytic system. Thomb Haemost 1988; 59: 495-499
  PubMedGoogle Scholar
• 6 Andreotti F, Davies GJ, Hackett DR, Khan MI, DeBart ACW, Aber VR, Maseri A, Kluft C. Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death and stroke. Am J Cardiol 1988; 62: 635-637
  CrossrefPubMedGoogle Scholar
• 7 Muller JE, Tofler GH, Stone PH. Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 1989; 79: 733-743
  CrossrefPubMedGoogle Scholar
• 8 Moser KM. Pulmonary Thromboembolism. In: Harrison’s Principles of Internal Medicine Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB, Fauci AS. eds McGraw-Hill; New York: 1987: 1105-1111
• 9 Keber D. The increase of leg fibrinolytic potential after reduction of hydrostatic stimulus. Thromb Haemost 1983; 50: 731-734
  Article in Thieme ConnectPubMedGoogle Scholar
• 10 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-247
  CrossrefPubMedGoogle Scholar
• 11 Naito K, Aoki N. Assay of a2-plasmin inhibitor activity by means of a plas-min specific tripeptide substrate. Thromb Res 1978; 12: 1147-1156
  CrossrefPubMedGoogle Scholar
• 12 Williams C, Chase M. Methods in immunology and immunochemistry, Academic Press, New York. 1971: 214
  PubMedGoogle Scholar
• 13 Schleef R, Sinha M, Loskutoff D. Immunoradiometric assay to measure the binding of a specific inhibitor to tissue-type plasminogen activator. J Lab Clin Med 1985; 106: 408-415
  PubMedGoogle Scholar
• 14 Nilsson K, Rosen S, Friberger P. A new kit for the determination of tissue plasminogen activator and its inhibitor in blood. Fibrinolysis 1987; 1: 163-168
  PubMedGoogle Scholar
• 15 Dandliker WB, deSaussure VA. Review Article: Fluorescence polarization in immunochemistry. Immunochemistry 1970; 7: 799-828
  CrossrefPubMedGoogle Scholar
• 16 Nishijima MK, Breslow MJ, Raff H, Traystman RJ. Regional adrenal blood flow during hypoxia in anesthetized, ventilated dogs. Am J Physiol 1989; 256: H94-H100
  PubMedGoogle Scholar
• 17 Rosenfeld BA, Faraday N, Campbell D, Dorman T, Clarkson K, Siedler A, Breslow MJ, Bell W. Perioperative platelet reactivity and the effects of clo-nidine. Anesthesiology 1993; 79: 255-261
  CrossrefPubMedGoogle Scholar
• 15 Sors H, Pradelles P, Dray F, Rigaud M, Maclouf J, Bernard P. Analytical methods for thromboxane B2 measurement and validation of radioimmunoassay by gas liquid chromatography-mass spectrometry. Prostaglandins 1978; 16: 277-290
  CrossrefPubMedGoogle Scholar
• 19 Virchow R. Phlogose und Thrombose im GefaBsystem. NC Abhandlungen, Wissenschaftliche Medicin. Virchow, R. ed. Von Meidinger Sohn, Frankfurt 1856; 458-636
  PubMedGoogle Scholar
• 20 Weitzman ED, Fukushima D, Nogeire C, Roffwarg H, Gallagher TF, Heilman L. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinology 1971; 33: 14-22
  CrossrefPubMedGoogle Scholar
• 21 Linsell CR, Lightman SL, Mullen PE, Brown MJ, Causon RC. Circadian rhythms of epinephrine and norepinephrine in man. J Clin Endocrinol Me-tab 1985; 60: 1210-1215
  CrossrefPubMedGoogle Scholar
• 22 Petralito A, Gibiino S, Miano MF, Mangiafico RA, Cuffari MA, Fiore CE. Daily modifications of plasma fibrinogen, platelets aggregation, Howell’s time, PTT, TT, and antithrombin III in normal subjects and in patients with vascular disease. Chronobiologia 1982; 9: 195-201
  PubMedGoogle Scholar
• 23 Ardlie NG, Cameron HA, Garrett J. Platelet activation by circulating levels of hormones: A possible link in coronary heart disease. Thromb Res 1984; 36: 315-322
  CrossrefPubMedGoogle Scholar
• 24 Schleef RR, Higgins DL, Pillemer E, Levitt LJ. Bleeding diathesis due to decreased functional activity of type 1 plasminogen activator inhibitor. J Clin Invest 1989; 83: 1747-1752
  CrossrefPubMedGoogle Scholar
• 25 van Mourik JA, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. J Biol Chem 1984; 259: 14914-14921
  PubMedGoogle Scholar
• 26 Konkle BA, Schuster SJ, Kelly MD, Harjes K, Hassett DE, Bohner M, Ta-vassoli M. Plasminogen activator inhibitor-1 messenger RNA expression is induced in rat hepatocytes in vivo by dexamethasone. Blood 1992; 79: 2636-2642
  PubMedGoogle Scholar
• 27 Isacson S. Effect of prednisolone on the coagulation and fibrinolytic systems. Scand J Haemat 1970; 7: 212-216
  PubMedGoogle Scholar
• 28 Aillaud MF, Juhan-Vague I, Alessi MC, Marecal M, Vinson MF, Amaud C, Vague P, Collen D. Increased PA-inhibitor levels in the postoperative period - no cause-effect relation with increased cortisol. Thromb Haemost 1985; 54: 466-468
  Article in Thieme ConnectPubMedGoogle Scholar
• 29 Rosing DR, Brakman P, Redwood DR, Goldstein RE, Beiser GD, Astrup T, Epstein SE. Blood fibrinolytic activity in man. Diurnal variation and the response to varying intensities of exercise. Cir Res 1970; 27: 171-184
  CrossrefPubMedGoogle Scholar