Download PDF
Thromb Haemost 2012; 108(03): 499-507
DOI: 10.1160/TH12-04-0225
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Levels of prolactin in relation to coagulation factors and risk of venous thrombosis

Results of a large population-based case-control study (MEGA-study)
Danka J. F. Stuijver
1   Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands
2   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Jan Debeij
3   Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands
,
Bregje van Zaane
1   Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands
2   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Olaf M. Dekkers
3   Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands
4   Department of Endocrinology and Metabolism, Leiden University Medical Center, the Netherlands
,
Jan W. A. Smit
4   Department of Endocrinology and Metabolism, Leiden University Medical Center, the Netherlands
,
Harry R. Büller
2   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Frits R. Rosendaal
3   Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands
5   Department of Thrombosis and Haemostasis, Leiden University Medical Center, the Netherlands
6   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, the Netherlands
,
Victor E. A. Gerdes
1   Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands
2   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Suzanne C. Cannegieter
3   Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands
5   Department of Thrombosis and Haemostasis, Leiden University Medical Center, the Netherlands
› Author Affiliations
Further Information

Publication History

Received: 04 April 2012

Accepted after minor revision: 19 May 2012

Publication Date:
25 November 2017 (online)

    Permissions and Reprints

Summary

The pituitary hormone prolactin is thought to influence coagulation. We aimed to study the relation between prolactin levels, coagulation factors and risk of venous thrombosis (VT). We used data from a large population based case-control study into aetiology of first VT (MEGA-study). Prolactin levels were determined in 2,068 patients with VT and 2,785 age- and sex matched control subjects. The relation between levels of coagulation factors and prolactin was studied among the controls. In addition, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for the risk of VT for different cut-off points of prolactin levels based on percentiles determined in the controls. Restricted analysis was performed among cases in whom blood was sampled within six months after VT. We found a rise in factor VIII and von Willebrand factor with increasing levels of prolactin in the controls. An increased risk of VT was observed when blood was sampled within six months after thrombosis (OR 2.9, 95%CI 1.1–8.1) for prolactin levels above the 99th percentile (42.6 μg/l) relative to levels between the 20th to 80th percentile. When blood was sampled more than six months after VT no clear association could be observed (OR 1.3, 95%CI 0.7–2.3). In conclusion, we found a modest association between pro-lactin and symptomatic venous thromboembolism, particularly when blood was sampled close to the event. This may be explained by a causal relation or by prolactin being a marker of stress due to the thrombotic event.

Keywords

Coagulation - fibrinolysis - venous thrombosis - risk factors - prolactin
 

  • References

  • 1 Ageno W, Squizzato A, Garcia D. et al. Epidemiology and risk factors of venous thromboembolism. Semin Thromb Hemost 2006; 32: 651-658.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Hagg S, Spigset O. Antipsychotic-induced venous thromboembolism: a review of the evidence. CNS Drugs 2002; 16: 765-776.
    CrossrefPubMedGoogle Scholar
  • 3 Heit JA, Kobbervig CE, James AH. et al. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143: 697-706.
    CrossrefPubMedGoogle Scholar
  • 4 Pomp ER, Lenselink AM, Rosendaal FR. et al. Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. J Thromb Haemost 2008; 06: 632-637.
    CrossrefPubMedGoogle Scholar
  • 5 Vandenbroucke JP, Rosing J, Bloemenkamp KW. et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med 2001; 344: 1527-1535.
    CrossrefPubMedGoogle Scholar
  • 6 Zornberg GL, Jick H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet 2000; 356: 1219-1223.
    CrossrefPubMedGoogle Scholar
  • 7 Erem C, Kocak M, Nuhoglu I. et al. Blood coagulation, fibrinolysis and lipid profile in patients with prolactinoma. Clin Endocrinol 2010; 73: 502-507.
    PubMedGoogle Scholar
  • 8 Wallaschofski H, Kobsar A, Koksch M. et al. Prolactin receptor signaling during platelet activation. Horm Metab Res 2003; 35: 228-235.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 van Zaane B, Squizzato A, Reuwer AQ. et al. Prolactin and venous thrombosis: indications for a novel risk factor?. Arterioscler Thromb Vasc Biol 2011; 31: 672-677.
    CrossrefPubMedGoogle Scholar
  • 10 Simon T, Beau Yon de Jonage-Canonico, Oger E. et al. EStrogen and THrom-boEmbolism Risk (ESTHER) Study Group. Indicators of lifetime endogenous estrogen exposure and risk of venous thromboembolism. J Thromb Haemost 2006; 04: 71-76.
    PubMedGoogle Scholar
  • 11 Horrobin DF, McNeilly AS, Jackson FS. et al. Letter: Prolactin and myocardial infarction. Lancet 1973; 02: 1261.
    PubMedGoogle Scholar
  • 12 Raaz D, Wallaschofski H, Stumpf C. et al. Increased prolactin in acute coronary syndromes as putative Co-activator of ADP-stimulated P-selectin expression. Horm Metab Res 2006; 38: 767-772.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Weizman R, Eldar M, Hod H. et al. Effects of uncomplicated acute myocardial infarction on biochemical parameters of stress and sexual function. Psychosomatics 1991; 32: 275-279.
    CrossrefPubMedGoogle Scholar
  • 14 Bezemer ID, Doggen CJ, Vos HL. et al. No association between the common MTHFR 677C->T polymorphism and venous thrombosis: results from the MEGA study. Arch Intern Med 2007; 167: 497-501.
    CrossrefPubMedGoogle Scholar
  • 15 Van Stralen KJ, Rosendaal FR, Doggen CJ. Minor injuries as a risk factor for venous thrombosis. Arch Intern Med 2008; 168: 21-26.
    CrossrefPubMedGoogle Scholar
  • 16 Wallaschofski H, Donne M, Eigenthaler M. et al. PRL as a novel potent cofactor for platelet aggregation. J Clin Endocrinol Metab 2001; 86: 5912-5919.
    CrossrefPubMedGoogle Scholar
  • 17 Chikanza IC, Grossman AB. Neuroendocrine immune responses to inflammation: the concept of the neuroendocrine immune loop. Baillieres Clin Rheumatol 1996; 10: 199-225.
    CrossrefPubMedGoogle Scholar
  • 18 Webster Marketon JI, Glaser R. Stress hormones and immune function. Cell Immunol 2008; 252: 16-26.
    CrossrefPubMedGoogle Scholar
  • 19 Heida NM, Schafer K, Konstantinides S. Prolactin as a modulator of platelet function and thrombosis: the end of the story, or a new beginning?. Thromb Haemost 2009; 101: 991-992.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Wallaschofski H, Kobsar A, Sokolova O. et al. Co-activation of platelets by prolac-tin or leptin--pathophysiological findings and clinical implications. Horm Metab Res 2004; 36: 1-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Wallaschofski H, Kobsar A, Sokolova O. et al. Differences in platelet activation by prolactin and leptin. Horm Metab Res 2004; 36: 453-457.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Atmaca A, Gurlek A, Dagdelen S. et al. Hyperprolactinemia of pregnancy is not associated with increased in vivo platelet activity and shortened in vitro bleeding times. Exp Clin Endocrinol Diabetes 2006; 14: 188-191.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Reuwer AQ, Nieuwland R, Fernandez I. et al. Prolactin does not affect human platelet aggregation or secretion. Thromb Haemost 2009; 101: 1119-1127.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Gordon EM, Hellerstein HK, Ratnoff OD. et al. Augmented Hageman factor and prolactin titers, enhanced cold activation of factor VII, and spontaneous shortening of prothrombin time in survivors of myocardial infarction. J Lab Clin Med 1987; 109: 409-413.
    PubMedGoogle Scholar
  • 25 Nishino Y. Hormonal control of prothrombin synthesis in rat liver microsomes, with special reference to the role of estradiol, testosterone and prolactin. Arch Toxicol Suppl 1979; 02: 397-402.
    PubMedGoogle Scholar
  • 26 Lwaleed BA, Bass PS. Tissue factor pathway inhibitor: structure, biology and involvement in disease. J Pathol 2006; 208: 327-339.
    CrossrefPubMedGoogle Scholar
  • 27 Zakai NA, Lutsey PL, Folsom AR. et al. Total tissue factor pathway inhibitor and venous thrombosis. The Longitudinal Investigation of Thromboembolism Etiology. Thromb Haemost 2010; 104: 207-212.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Mohankumar SM, Kasturi BS, Shin AC. et al. Chronic estradiol exposure induces oxidative stress in the hypothalamus to decrease hypothalamic dopamine and cause hyperprolactinemia. Am J Physiol Regul Integr 2011; 300: 693-699.
    CrossrefPubMedGoogle Scholar
  • 29 Frantz AG. Prolactin. N Engl J Med 1978; 298: 201-207.
    CrossrefPubMedGoogle Scholar