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Thromb Haemost 2012; 107(01): 22-29
DOI: 10.1160/TH11-07-0481
Review Article
Schattauer GmbH

Haemostatic variables during normal menstrual cycle

A systematic review
H. Marieke Knol
1   Division of Haemostasis and Thrombosis, Department of Haematology, University Medical Centre Groningen, Groningen, The Netherlands
2   Department of Obstetrics and Gynaecology, University Medical Centre Groningen, Groningen, The Netherlands
,
Ramses F. J. Kemperman
3   Department of Laboratory Medicine, University Medical Centre Groningen, Groningen, The Netherlands
,
Hanneke C. Kluin-Nelemans
1   Division of Haemostasis and Thrombosis, Department of Haematology, University Medical Centre Groningen, Groningen, The Netherlands
,
André B. Mulder
3   Department of Laboratory Medicine, University Medical Centre Groningen, Groningen, The Netherlands
,
Karina Meijer
1   Division of Haemostasis and Thrombosis, Department of Haematology, University Medical Centre Groningen, Groningen, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 14 July 2011

Accepted after minor revision: 24 October 2011

Publication Date:
20 November 2017 (online)

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Summary

For a number of haemostatic factors menstrual cycle variation has been studied. Such variation could have clinical implications for the timing of haemostatic testing in women. It was our objective to systematically review the literature about evidence for timing of haemostatic testing during menstrual cycle.We searched MEDLINE, EMBASE and the Cochrane library to identify studies that measured haemostatic variables [platelet function, von Willebrand factor (VWF), factor VIII (FVIII), factor IX (FIX), factor XI (FXI), factor XIII (FXIII), D-dimer, plasminogen activator inhibitor-I (PAI-I), tissue plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), α2-antiplasmin and fibrinogen] during normal menstrual cycle without hormonal contraceptives. Two investigators independently selected studies, and abstracted data in duplicate. We identified 1,046 studies of which we included 30 studies (25 longitudinal and 5 cross-sectional studies). All studies reported on haemostatic variables during menstrual cycle. Overall, most of the studies found no cyclic variation in VWF, FVIII, FXI, FXIII, fibrinolytic factors (PAI, t-PA, uPA, D-dimer and α2-antiplasmin) and fibrinogen. However, in studies where these variables showed any variation, they reached the lowest levels during menstrual and early follicular phase, especially for VWF, FVIII and platelet function tests. In conclusion, the optimal timing for haemostatic testing during menstrual cycle seems to be menstrual and early follicular phase.

Keywords

Menstrual cycle - haemostasis - von Willebrand factor - haemostatic variables
 

  • References

  • 1 Kadir RA, Economides DL, Sabin CA. et al. Frequency of inherited bleeding disorders in women with menorrhagia. Lancet 1998; 351: 485-489.
    CrossrefPubMedGoogle Scholar
  • 2 Kouides PA, Kadir RA. Menorrhagia associated with laboratory abnormalities of hemostasis: epidemiological, diagnostic and therapeutic aspects. J Thromb Haemost 2007; 05 (01) 175-182.
    CrossrefPubMedGoogle Scholar
  • 3 James AH, Kouides PA, Abdul-Kadir R. et al. Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel. Am J Obstet Gynecol 2009; 201: 12-18.
    PubMedGoogle Scholar
  • 4 James AH, Ragni MV, Picozzi VJ. Bleeding disorders in premenopausal women: (another) public health crisis for hematology?. Hematology Am Soc Hematol Educ Program 2006; 474-485.
    PubMedGoogle Scholar
  • 5 Philipp CS, Dilley A, Miller CH. et al. Platelet functional defects in women with unexplained menorrhagia. J Thromb Haemost 2003; 01: 477-484.
    CrossrefPubMedGoogle Scholar
  • 6 Shankar M, Lee CA, Sabin CA. et al. von Willebrand disease in women with menorrhagia: a systematic review. Br J Obstet Gynecol 2004; 111: 734-740.
    CrossrefPubMedGoogle Scholar
  • 7 Feuring M, Christ M, Roell A. et al. Alterations in platelet function during the ovarian cycle. Blood Coagul Fibrinolysis 2002; 13: 443-447.
    CrossrefPubMedGoogle Scholar
  • 8 Repina MA, Korzo TM, Zinina TA. Effect of hormone replacement therapy with femoston on hemostasis in peri- and postmenopausal women. Med Sci Monit 2002; 08: I78-I84.
    PubMedGoogle Scholar
  • 9 Roell A, Schueller P, Schultz A. et al. Effect of oral contraceptives and ovarian cycle on platelet function. Platelets 2007; 18: 165-170.
    CrossrefPubMedGoogle Scholar
  • 10 Blomback M, Eneroth P, Landgren BM. et al. On the intraindividual and gender variability of haemostatic components. Thromb Haemost 1992; 67: 70-75.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Blomback M, Landgren BM, Stiernholm Y. et al. The effect of progesterone on the haemostatic mechanism. Thromb Haemost 1997; 77: 105-108.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Giardina EG, Chen HJ, Sciacca RR. et al. Dynamic variability of hemostatic and fibrinolytic factors in young women. J Clin Endocrinol Metab 2004; 89: 6179-6184.
    CrossrefPubMedGoogle Scholar
  • 13 Jern C, Manhem K, Eriksson E. et al. Hemostatic responses to mental stress during the menstrual cycle. Thromb Haemost 1991; 66: 614-618.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Koh SC, Prasad RN, Fong YF. Hemostatic status and fibrinolytic response potential at different phases of the menstrual cycle. Clin Appl Thromb Hemost 2005; 11: 295-301.
    CrossrefPubMedGoogle Scholar
  • 15 Onundarson PT, Gudmundsdottir BR, Arnfinnsdottir AV. et al. Von Willebrand factor does not vary during normal menstrual cycle. Thromb Haemost 2001; 85: 183-184.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Miller CH, Dilley AB, Drews C. et al. Changes in von Willebrand factor and factor VIII levels during the menstrual cycle. Thromb Haemost 2002; 87: 1082-1083.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Kadir RA, Economides DL, Sabin CA. et al. Variations in coagulation factors in women: effects of age, ethnicity, menstrual cycle and combined oral contraceptive. Thromb Haemost 1999; 82: 1456-1461.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 He S, Silveira A, Hamsten A. et al. Haemostatic, endothelial and lipoprotein parameters and blood pressure levels in women with a history of preeclampsia. Thromb Haemost 1999; 81: 538-542.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Mandalaki T, Louizou C, Dimitriadou C. et al. Variations in factor VIII during the menstrual cycle in normal women. N Engl J Med 1980; 302: 1093-1094.
    PubMedGoogle Scholar
  • 20 Siegbahn A, Odlind V, Hedner U. et al. Coagulation and fibrinolysis during the normal menstrual cycle. Ups J Med Sci 1989; 94: 137-152.
    CrossrefPubMedGoogle Scholar
  • 21 Bolis PF, Franchi M, Marino L. et al. Serial detection of plasma-factor XIII levels during the ovulatory cycle and estroprogestative contraception. Clin Exp Obstet Gynecol 1982; 09: 22-25.
    PubMedGoogle Scholar
  • 22 Chung HC, Rha SY, Park JO. et al. Physiological and pathological changes of plasma urokinase-type plasminogen activator, plasminogen activator inhibitor-1, and urokinase-type plasminogen activator receptor levels in healthy females and breast cancer patients. Breast Cancer Res Treat 1998; 49: 41-50.
    CrossrefPubMedGoogle Scholar
  • 23 Jespersen J, Kluft C. Inhibition of tissue-type plasminogen activator in plasma of women using oral contraceptives and in normal women during a menstrual cycle. Thromb Haemost 1986; 55: 388-389.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Larsen LF, Andersen HR, Hansen AB. et al. Variation in risk indicators of cardiovascular disease during the menstrual cycle: an investigation of within-subject variations in glutathione peroxidase, haemostatic variables, lipids and lipoproteins in healthy young women. Scand J Clin Lab Invest 1996; 56: 241-249.
    CrossrefPubMedGoogle Scholar
  • 25 Ricci G, Cerneca F, Simeone R. et al. Impact of highly purified urinary FSH and recombinant FSH on haemostasis: an open-label, randomized, controlled trial. Hum Reprod 2004; 19: 838-848.
    CrossrefPubMedGoogle Scholar
  • 26 Spona J, Feichtinger W, Kindermann C. et al. Double-blind, randomized, placebo controlled study on the effects of the monophasic oral contraceptive containing 30 micrograms ethinyl estradiol and 2.00 mg dienogest on the hemostatic system. Contraception 1997; 56: 67-75.
    CrossrefPubMedGoogle Scholar
  • 27 Jespersen J, Sidelmann J. Individual levels of plasma alpha 2-antiplasmin and alpha 2-macroglobulin during the normal menstrual cycle and in women on oral contraceptives low in oestrogen. Thromb Haemost 1983; 50: 581-585.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Dorr PJ, Brommer EJ, Dooijewaard G. et al. Parameters of fibrinolysis in peritoneal fluid and plasma in different stages of the menstrual cycle. Thromb Haemost 1993; 70: 873-875.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Toth B, Nikolajek K, Rank A. et al. Gender-specific and menstrual cycle dependent differences in circulating microparticles. Platelets 2007; 18: 515-521.
    CrossrefPubMedGoogle Scholar
  • 30 Buchan PC, Macdonald HN. Altered haemorheology in oral-contraceptive users. Br Med J 1980; 280: 978-979.
    CrossrefPubMedGoogle Scholar
  • 31 Cederblad G, Hahn L, Korsan-Bengtsen K. et al. Variations in blood coagulation, fibrinolysis, platelet function and various plasma proteins during the menstrual cycle. Haemostasis 1977; 06: 294-302.
    PubMedGoogle Scholar
  • 32 Dapper DV, Didia BC. Haemorheological changes during the menstrual cycle. East Afr Med J 2002; 79: 181-183.
    PubMedGoogle Scholar
  • 33 Gaur S, Datta S, Bhargava RP. Fibrinolytic activity, fibrinogen content, prothrombin time and clotting time during menstrual cycle. Indian J Physiol Pharmacol 1982; 26: 152-156.
    PubMedGoogle Scholar
  • 34 Lebech AM, Kjaer A. Lipid metabolism and coagulation during the normal menstrual cycle. Horm Metab Res 1989; 21: 445-448.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Solerte SB, Fioravanti M, Spinillo A. et al. Association between hormonal and haemorheological changes during the menstrual cycle in healthy women. Br J Obstet Gynaecol 1988; 95: 1305-1308.
    CrossrefPubMedGoogle Scholar
  • 36 Lethagen S. Desmopressin in the treatment of women's bleeding disorders. Haemophilia 1999; 05: 233-237.
    CrossrefPubMedGoogle Scholar
  • 37 Gleeson NC. Cyclic changes in endometrial tissue plasminogen activator and plasminogen activator inhibitor type 1 in women with normal menstruation and essential menorrhagia. Am J Obstet Gynecol 1994; 171: 178-183.
    CrossrefPubMedGoogle Scholar