Chronobiological aspects in haematology

Authors: P. Švorc;  E. Švorcová 1
Authors‘ workplace: Ústav fyziológie, Lekárska fakulta UPJŠ, 1Klinika hematológie a onkohematológie, Univerzitná nemocnica L. Pasteura, tr. SNP 1, Košice
Published in: Transfuze Hematol. dnes,17, 2011, No. 2, p. 98-104.
Category: Comprehensive Reports, Original Papers, Case Reports


Man is exposed to the periodical processes of external environment practically with the synchronization of all his functions during the entire lifespan. The circadian rhythms (24 hour rhythms) are studied most frequently and they are demonstrated also in haematology. Detailed understanding of the circadian timing in fluctuation of some haematological functions in healthy man can have a clinical impact. In the present time, more and more information pass into foreground that changes, for example, in circadian oscillations of haemostatic system may lead to disturbance, resulting in either hypercoagulability and thrombosis or alternatively hypocoagulability and hemorrhage. Variables participating in haemostasis and thrombosis interact and their timing and phase relations may either contribute to maintaining the balance between procoagulant and anticoagulant factors or they may shift the balance in the direction of increased or decreased blood coagulation or thrombolysis. Therefore knowledge about circadian oscillations of haematological functions can serve for timing the more effective treatment of various blood diseases or can indicate that changes in timing of these functions can help to predict certain haematological disease. In the first part of the article we concentrated on elucidation of the basic terms, which are most frequently used in the chronobiological literature. The main objective of the article is to establish the existence of circadian variation in fundamental haematological processes, like haemopoesis, haemostasis and fibrinolysis in healthy persons.

Key words:
chronobiology, haematology


1. Steinbach G, Hilfenhaus M, Von Mayersbach H, et al. Circadian influences in clinical values in man. Arch Toxicol 1976; 36: 317-325.

2. Boning D, Schweigart U, Kunze M. Diurnal variations of protein and electrolyte concentrations and of acid base status in plasma and red cells of normal man. Eur J Appl Physiol Occup Physiol 1974; 32: 239-250.

3. Jones AR, Twedt D, Swaim W, et al. Diurnal change of blood count analytes in normal subjects. Amer J Clin Pathol 1996; 106: 723-727.

4. Touitou Y, Bogdan A, Haus E, et al. Modifications of circadian and circannual rhythms with aging. Exp Gerontol 1997; 32: 603-614.

5. McKee LC, Johnson LE, Lange RD. Circadian variation in reticulocyte counts and immuno detectable erythropoietin titers. Proc Soc Exp Biol Med 1974; 145: 1284-1287.

6. Gunga HC, Kirsch KA, Roecker L, et al. Erythropoietin regulations in humans under different environmental and experimental conditions. Respir Physiol Neurobiol 2007; 158: 287-297.

7. De Nicola P, Casale G, Riccotti MP, et al. Circadian rhythms of blood components in dementia senilis. Folia Haematologica: Internationales Magazin fur klinische und morphologische Blutforschung 1984; 111: 782-787.

8. Melchart D, Martin P, Hallek M, et al. Circadian variation of the phagocytic activity of polymorphonuclear leukocytes and of various other parameters in 13 healthy male adults. Chronobiol Int 1992; 9: 35-45.

9. Swoyer J, Irvine P, Sackett-Lundeen L, et al. Circadian hematologic time structure in the elderly. Chronobiol Int 1989; 6: 131-137.

10. Barkova EN, Nazarenko EV. Circadian dynamics of monocyte phagocytic activity in women during lactation complicated by iron deficiency. Bull Exp Biol Med 2005; 140: 29-32.

11. Wood PA, Hrushesky WJM, Klevecz R. Distinct circadian time structures characterize myeloid and erythroid progenitor and multipotential cell clonogenicity as well as marrow precursor proliferation dynamics. Exp Hematol 1998; 26: 523-533.

12. Mendez-Ferrer S, Chow A, Merad M, et al. Circadian rhythms influence hematopoietic stem cells. Curr Opinion Hematol 2009; 16: 235-242.

13. Smaaland R, Sothern RB, Laerum OD, et al. Rhythms in human bone marrow and blood cells. Chronobiol Int 2002; 19: 101-127.

14. Abrahamsen JF, Sothern RB, Sandberg S, et al. Circadian variations in human peripheral blood on days with and without bone marrow sampling and relation to bone marrow cell proliferation. Biol Rhythm Res 1999; 30: 29-53.

15. Manfredini R, Boari B, Smolensky MH, et al. Review: Circadian variation in stroke onset: Identical temporal pattern in ischemic and hemorrhagic events. Chronobiol Int 2005; 22: 417-453.

16. Anderson N, Feigin V, Bennett D, et al. Diurnal, weekly, and seasonal variations in stroke occurrence in a population-based study in Auckland, New Zealand. N Z Med J 2004; 117: U1078.

17. Ameriso SF, Mohler JG, Suarez M, et al. Morning reduction of cerebral vasomotor reactivity, Neurology 1994; 44: 1907-1909.

18. Haus E, Cusulos M, Sackett-Lundeen L, Swoyer J. Circadian variations in blood coagulation parameters, alpha-antitrypsin antigen and platelet aggregation and retention in clinically healthy subjects. Chronobiol Int 1990; 7: 203-216.

19. Dalby MC, Davidson SJ, Burman JF, Davies SW. Diurnal variation in platelet aggregation with the PFA-100 platelet function analysis. Platelets 2000; 11: 320-324.

20. Ündar L, Ertugrul C, Altunbas H, et at. Circadian variations in natural coagulation inhibitors protein C, protein S and antithrombin in healthy men: a possible association with interleukin-6. Thromb Haemost 1999; 81: 571-575.

21. Del Zar MM, Martinuzzo M, Falcon C, et al. Inhibition of human platelet aggregation and thromboxane-B2, production by melatonin evidence for a diurnal variation. J Clin Endocrinol Metab 1990; 70: 246-251.

22. Haus E. Chronobiology of hemostasis and inferences for the chronotherapy of coagulation disorders and thrombosis prevention. Adv Drug Deliv Rev 2007; 59: 966-984.

23. Jafri SM, VanRollins M, Ozawa T, et al. Circadian variation in platelet function in healthy volunteers. Amer J Cardiol 1992; 69: 951-954.

24. Jovicic A, Mandic S. Circadian variations of platelet aggregability and fibrinolytic activity in healthy subjects. Thromb Res 1991; 62: 65-74.

25. Andrews NP, Goldstein DS, Quyyumi AA. Effect of systemic alpha-2 adrenergic blockade on the morning increase in platelet aggregation in normal subjects. Am J Cardiol 1999; 84: 316-320.

26. Belch JJF. The role of the white blood cell in arterial disease. Blood Coagul Fibrinolysis 1990; 1: 183-192.

27. Bridges AB, Fisher TC, Scott N, et al. Circadian rhythm of white blood cell aggregation and free radical status in healthy volunteers. Free Radic Res Commun 1992; 16: 89-97.

28. Kapiotis S, Jilma B, Quehenberger P, et al. Morning hypercoagulability and hypofibrinolysis. Circulation 1997; 96: 19-21.

29. Iversen PO, Groot PDE, Hyeltnes N, et al. Impaired circadian variations of haemostatic and fibrinolytic parameters in tetraplegia. Br J Haematol 2002; 119: 1011-1016.

30. Hermida RC, Calvo C, Ayala DE, et al. Seasonal variation in plasma fibrinogen in dipper and non-dipper patients with mild-moderate essential hypertension. Med Clin (Barc) 2003; 121: 6-11.

31. Kanabrocki EL, Sothern RB, Bremner WF, et al. Weekly and yearly rhythms in plasma fibrinogen in hospitalized male military veterans. Am J Cardiol 1995; 76: 628-631.

32. Hodoglugil U, Gunaydin B, Yardim S, et al. Seasonal variation in the effect of a fixed dose of heparin on activated clotting time in patients prepared for open-heart surgery. Chronobiol Int 2001; 18: 865-873.

33. 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: 171-184.

34. Kofoed KF, Gleerup G, Hedman C, et al. The circadian variation in fibrinolytic activity is not related to posture. Thromb Res 1994; 73: 447-450.

35. Chomiki N, Henry M, Alessi MC, et al. Plasminogen activator inhibitor-1 expression in human liver and healthy or atherosclerotic vessel walls. Thromb Haemost 1994; 72: 44-53.

36. Brogren H, Karlsson L, Andersson M, et al. Platelets synthesize large amounts of active plasminogen activator inhibitor 1. Blood 2004; 104: 3943-3948.

37. Sprengers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69: 381-387.

38. Andreotti F, Kluft C. Circadian variation of fibrinolytic activity in blood. Chronobiol Int 1991; 8: 336-351.

39. McNamara P, Seo SP, Rudic RD, et al. Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock. Cell 2001; 105: 877-889.

40. Hoekstra T, Geleijnse JM, Schouten EG, et al. Diurnal variation in PAI-1 activity predominantly confirned to the 4G-allele of the PAI-1 gene. Thromb Haemost 2002; 88: 794-798.

41. Van der Bom JG, Bots ML, Haverkate F, et al. The 4G5G polymorphism in the gene for PAI-1 and the circadian oscillation of plasma PAI-1. Blood 2003; 101: 1841-1844.

42. Von Kanel R, Jain S, Mills PJ, et al. Relation of nocturnal blood pressure dipping to cellular adhesion, inflammation and hemostasis. J Hypertens 2004; 22: 2087-2093.

43. Imeson JD, Meade TW, Steward GM. Day by day variation in fibrinolytic activity and in mortality from ischemic heart disease. Int J Epidemiol 1987; 16: 626-627.

44. Nicolau GY, Haus E, Popescu M, et al. Circadian, weekly, and seasonal variations in cardiac mortality, blood pressure, and catecholamine excretion. Chronobiol Int 1991; 8: 149-159.

Haematology Internal medicine Clinical oncology
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account