This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kapiotis, S. Articles by Speiser, W. Search for Related Content PubMed PubMed Citation Articles by Kapiotis, S. Articles by Speiser, W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL

(Circulation. 1997;96:19-21.)
© 1997 American Heart Association, Inc.

Articles

Morning Hypercoagulability and Hypofibrinolysis

Diurnal Variations in Circulating Activated Factor VII, Prothrombin Fragment F₁₊₂, and Plasmin–Plasmin Inhibitor Complex

Stylianos Kapiotis, MD; Bernd Jilma, MD; Peter Quehenberger, MD; Katharina Ruzicka, MD; Sylvia Handler, MT; ; Wolfgang Speiser, MD

From the Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.K., P.Q., K.R., S.H., W.S.) and the Department of Clinical Pharmacology (B.J.), University of Vienna, Austria.

Correspondence to Wolfgang Speiser, MD, Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, General Hospital Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail stylianos.kapiotis{at}univie.ac.at

Background Diurnal fluctuations of blood coagulation and fibrinolysis activity are thought to play a role in the observed circadian variation in the frequency of onset of acute cardiovascular events. In the present study, the diurnal variations in blood coagulation and fibrinolysis activity were investigated in 10 young, healthy control subjects by use of specific molecular activation markers.

Methods and Results The plasma levels of activated factor FVII (FVIIa), the active portion of the main coagulation activator, decreased during the day (8 AM: 2.03 ng/mL, CI 1.16 to 2.88 ng/mL; 8 PM: 1.16 ng/mL, CI 0.81 to 1.5 ng/mL; P=.005), whereas FVII antigen did not change significantly. In parallel with the diurnal variations of FVIIa, we found a decrease of prothrombin fragment F₁₊₂ (8 AM: 0.97 nmol/L, CI 0.79 to 1.15 nmol/L; 8 PM: 0.78 nmol/L, CI 0.64 to 0.93 nmol/L; P=.005), a molecular marker of intravasal thrombin generation. Evidence for a possible functional relevance of circulating FVIIa was found because this parameter was significantly correlated with prothrombin fragment F₁₊₂ in 72 fasting healthy individuals (r=.29, P=.011). Plasminogen activator inhibitor-1 levels decreased (8 AM: 9.9 ng/mL, CI 7.7 to 12.1 ng/mL; 8 PM: 5.4 ng/mL, CI 3.8 to 6.9 ng/mL; P<.005), whereas plasmin–plasmin inhibitor complex levels, representing the degree of intravascular plasmin generation, concomitantly increased (8 AM: 235 µg/L, CI 198 to 272 µg/L; 8 PM: 449 µg/L, CI 391 to 507 µg/L; P=.008).

Conclusions Our data suggest that the diurnal changes in the plasma levels of activators and inhibitors of coagulation and fibrinolysis lead to corresponding changes in the activity state of these systems, leading to morning hypercoagulability and hypofibrinolysis.

Key Words: circadian rhythm • fibrinolysis • coagulation

This article has been cited by other articles:

				J. P. Ornato, J. E. Muller, E. S. Froelicher, and R. A. Kloner Task Force II: Indirect and Secondary Cardiovascular Effects of Biological Terrorism Agents and Diseases J. Am. Coll. Cardiol., March 27, 2007; 49(12): 1389 - 1397. [Full Text] [PDF]

				M. D. de Kruif, L. C. Lemaire, I. A. Giebelen, M. A. D. van Zoelen, J. M. Pater, P. S. van den Pangaart, A. P. Groot, A. F. de Vos, P. J. Elliott, J. C. M. Meijers, et al. Prednisolone Dose-Dependently Influences Inflammation and Coagulation during Human Endotoxemia J. Immunol., February 1, 2007; 178(3): 1845 - 1851. [Abstract] [Full Text] [PDF]

				B. Amasyali, K. Aytemir, S. Kose, A. Kilic, G. Abali, A. Iyisoy, H. Kursaklioglu, M. Turan, N. Bingol, E. Isik, et al. Admission Plasma Leptin Level Strongly Correlates With the Success of Thrombolytic Therapy in Patients With Acute Myocardial Infarction Angiology, January 1, 2007; 57(6): 671 - 680. [Abstract] [PDF]

				J. Wang, L. Yin, and M. A. Lazar The Orphan Nuclear Receptor Rev-erb{alpha} Regulates Circadian Expression of Plasminogen Activator Inhibitor Type 1 J. Biol. Chem., November 10, 2006; 281(45): 33842 - 33848. [Abstract] [Full Text] [PDF]

				W. D. Toff, C. I. Jones, I. Ford, R. J. Pearse, H. G. Watson, S. J. Watt, J. A. S. Ross, D. P. Gradwell, A. J. Batchelor, K. R. Abrams, et al. Effect of Hypobaric Hypoxia, Simulating Conditions During Long-Haul Air Travel, on Coagulation, Fibrinolysis, Platelet Function, and Endothelial Activation JAMA, May 17, 2006; 295(19): 2251 - 2261. [Abstract] [Full Text] [PDF]

				C. Bertolucci, M. Pinotti, I. Colognesi, A. Foa, F. Bernardi, and F. Portaluppi Circadian Rhythms in Mouse Blood Coagulation J Biol Rhythms, June 1, 2005; 20(3): 219 - 224. [Abstract] [PDF]

				M. Pinotti, C. Bertolucci, F. Portaluppi, I. Colognesi, E. Frigato, A. Foa, and F. Bernardi Daily and Circadian Rhythms of Tissue Factor Pathway Inhibitor and Factor VII Activity Arterioscler. Thromb. Vasc. Biol., March 1, 2005; 25(3): 646 - 649. [Abstract] [Full Text] [PDF]

				J. G. van der Bom, M. L. Bots, F. Haverkate, C. Kluft, and D. E. Grobbee The 4G5G polymorphism in the gene for PAI-1 and the circadian oscillation of plasma PAI-1 Blood, March 1, 2003; 101(5): 1841 - 1844. [Abstract] [Full Text] [PDF]

				U. Derhaschnig, A. N. Laggner, M. Roggla, M. M. Hirschl, S. Kapiotis, C. Marsik, and B. Jilma Evaluation of Coagulation Markers for Early Diagnosis of Acute Coronary Syndromes in the Emergency Room Clin. Chem., November 1, 2002; 48(11): 1924 - 1930. [Abstract] [Full Text] [PDF]

				R. H. Mehta, R. Manfredini, F. Hassan, U. Sechtem, E. Bossone, J. K. Oh, J. V. Cooper, D. E. Smith, F. Portaluppi, M. Penn, et al. Chronobiological Patterns of Acute Aortic Dissection Circulation, August 27, 2002; 106(9): 1110 - 1115. [Abstract] [Full Text] [PDF]

				J. A. Shaw, J. P. F. Chin-Dusting, B. A. Kingwell, and A. M. Dart Diurnal Variation in Endothelium-Dependent Vasodilatation Is Not Apparent in Coronary Artery Disease Circulation, February 13, 2001; 103(6): 806 - 812. [Abstract] [Full Text] [PDF]

				T. Pernerstorfer, U. Hollenstein, J.-B. Hansen, M. Knechtelsdorfer, P. Stohlawetz, W. Graninger, H.-G. Eichler, W. Speiser, and B. Jilma Heparin Blunts Endotoxin-Induced Coagulation Activation Circulation, December 21, 1999; 100(25): 2485 - 2490. [Abstract] [Full Text] [PDF]

				E Goldhammer, L Kharash, and E G Abinader Circadian fluctuations in the efficacy of thrombolysis with streptokinase Postgrad. Med. J., November 1, 1999; 75(889): 667 - 671. [Abstract] [Full Text]

				J. W. Sayer, C. Gutteridge, D. Syndercombe-Court, P. Wilkinson, and A. D. Timmis Circadian activity of the endogenous fibrinolytic system in stable coronary artery disease: effects of beta-adrenoreceptor blockers and angiotensin-converting enzyme inhibitors J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1962 - 1968. [Abstract] [Full Text] [PDF]