PDF herunterladen
CC BY 4.0 · Thromb Haemost 2020; 120(02): 243-252
DOI: 10.1055/s-0039-3402808
Coagulation and Fibrinolysis

Reduced Plasma Magnesium Levels in Type-1 Diabetes Associate with Prothrombotic Changes in Fibrin Clotting and Fibrinolysis

Amélie I. S. Sobczak
1   School of Medicine, University of St Andrews, St Andrews, United Kingdom
,
Fladia A. Phoenix
2   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
,
Samantha J. Pitt
1   School of Medicine, University of St Andrews, St Andrews, United Kingdom
,
Ramzi A. Ajjan
2   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
,
Alan J. Stewart 
1   School of Medicine, University of St Andrews, St Andrews, United Kingdom
› Institutsangaben Funding This research was funded by the British Heart Foundation, grant numbers PG/15/9/31270 and FS/15/42/3155. The study sponsor was not involved in the design of the study, the collection, analysis, or interpretation of data.
› Weitere Informationen
   Lizenzen und Reprints

Abstract

Individuals with type-1 diabetes mellitus (T1DM) have a higher risk of thrombosis and low plasma magnesium concentrations. As magnesium is a known regulator of fibrin network formation, we investigated potential associations between fibrin clot properties and plasma magnesium concentrations in 45 individuals with T1DM and 47 age- and sex-matched controls without diabetes. Fibrin clot characteristics were assessed using a validated turbidimetric assay and associations with plasma magnesium concentration were examined. Plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and lipids were measured and fibrin fiber diameters assessed using scanning electron microscopy. Fibrin clot maximum absorbance was unchanged in subjects with T1DM compared with controls, while lysis time was prolonged (p = 0.0273). No differences in fibrin fiber diameters or in lipid profile were observed between T1DM and controls. PAI-1 concentration was lower in the T1DM group compared with the controls (p = 0.0232) and positively correlated with lysis time (p = 0.0023). Plasma magnesium concentration was lower in the T1DM group compared with controls (p < 0.0001). Magnesium concentration negatively correlated with clot maximum absorbance (p = 0.0215) and lysis time (p = 0.0464). A turbidimetric fibrin clot lysis assay performed in a purified system that included PAI-1 and 0 to 3.2 mM Mg2+ showed a shortening of lysis time with increasing Mg2+ concentrations (p = 0.0004). Our findings reveal that plasma magnesium concentration is associated with changes in fibrin clot and lysis parameters.

Keywords

clot lysis - coagulation - metal homeostasis - plasminogen activator inhibitor-1 - thrombosis


Publikationsverlauf

Eingereicht: 19. August 2019

Angenommen: 11. November 2019

Artikel online veröffentlicht:
03. Januar 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Al Alawi AM, Majoni SW, Falhammar H. Magnesium and human health: perspectives and research directions. Int J Endocrinol 2018; 2018: 9041694
    Google Scholar
  • 2 Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J. Incidence of childhood type 1 diabetes worldwide. Diabetes mondiale (DiaMond) project group. Diabetes Care 2000; 23 (10) 1516-1526
    Google Scholar
  • 3 Schofield J, Ho J, Soran H. Cardiovascular risk in type 1 diabetes mellitus. Diabetes Ther 2019; 10 (03) 773-789
    Google Scholar
  • 4 Huxley RR, Peters SA, Mishra GD, Woodward M. Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2015; 3 (03) 198-206
    Google Scholar
  • 5 Sekiya F, Yoshida M, Yamashita T, Morita T. Magnesium(II) is a crucial constituent of the blood coagulation cascade. Potentiation of coagulant activities of factor IX by Mg2+ ions. J Biol Chem 1996; 271 (15) 8541-8544
    Google Scholar
  • 6 de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev 2015; 95 (01) 1-46
    Google Scholar
  • 7 Anstall HB, Hayward GH, Huntsman RG, Weitzman D, Lehmann H. The effect of magnesium on blood coagulation in human subjects. Lancet 1959; 1 (7077): 814-815
    Google Scholar
  • 8 Mannuß S, Schuff-Werner P, Dreißiger K, Kohlschein P. Magnesium sulfate as an alternative in vitro anticoagulant for the measurement of platelet parameters?. Am J Clin Pathol 2016; 145 (06) 806-814
    Google Scholar
  • 9 Sobczak AIS, Stefanowicz F, Pitt SJ, Ajjan RA, Stewart AJ. Total plasma magnesium, zinc, copper and selenium concentrations in type-I and type-II diabetes. Biometals 2019; 32 (01) 123-138
    Google Scholar
  • 10 Efstratiadis G, Sarigianni M, Gougourelas I. Hypomagnesemia and cardiovascular system. Hippokratia 2006; 10 (04) 147-152
    Google Scholar
  • 11 Serebruany VL, Herzog WR, Edenbaum LR, Shustov AR, Gurbel PA. Changes in the haemostatic profile during magnesium deficiency in swine. Magnes Res 1996; 9 (03) 155-163
    Google Scholar
  • 12 Lemkes BA, Hermanides J, Devries JH, Holleman F, Meijers JC, Hoekstra JB. Hyperglycemia: a prothrombotic factor?. J Thromb Haemost 2010; 8 (08) 1663-1669
    Google Scholar
  • 13 Hooper JM, Stuijver DJ, Orme SM. et al. Thyroid dysfunction and fibrin network structure: a mechanism for increased thrombotic risk in hyperthyroid individuals. J Clin Endocrinol Metab 2012; 97 (05) 1463-1473
    Google Scholar
  • 14 Hess K, Alzahrani SH, Mathai M. et al. A novel mechanism for hypofibrinolysis in diabetes: the role of complement C3. Diabetologia 2012; 55 (04) 1103-1113
    Google Scholar
  • 15 De Feo P, Gaisano MG, Haymond MW. Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans. J Clin Invest 1991; 88 (03) 833-840
    Google Scholar
  • 16 Agren A, Jörneskog G, Elgue G, Henriksson P, Wallen H, Wiman B. Increased incorporation of antiplasmin into the fibrin network in patients with type 1 diabetes. Diabetes Care 2014; 37 (07) 2007-2014
    Google Scholar
  • 17 Tehrani S, Jörneskog G, Ågren A, Lins PE, Wallén H, Antovic A. Fibrin clot properties and haemostatic function in men and women with type 1 diabetes. Thromb Haemost 2015; 113 (02) 312-318
    Google Scholar
  • 18 Adly AA, Elbarbary NS, Ismail EA, Hassan SR. Plasminogen activator inhibitor-1 (PAI-1) in children and adolescents with type 1 diabetes mellitus: relation to diabetic micro-vascular complications and carotid intima media thickness. J Diabetes Complications 2014; 28 (03) 340-347
    Google Scholar
  • 19 Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost 2005; 3 (08) 1879-1883
    Google Scholar
  • 20 Aso Y. Plasminogen activator inhibitor (PAI)-1 in vascular inflammation and thrombosis. Front Biosci 2007; 12: 2957-2966
    Google Scholar
  • 21 Wolberg AS, Campbell RA. Thrombin generation, fibrin clot formation and hemostasis. Transfus Apheresis Sci 2008; 38 (01) 15-23
    Google Scholar
  • 22 Jankun J, Skrzypczak-Jankun E, Lipinski B. Complex function of magnesium in blood clot formation and lysis. Cent Eur J Immunol 2013; 38 (02) 149-153
    Google Scholar
  • 23 Lacal J, García-Fontana C, Callejo-García C, Ramos JL, Krell T. Physiologically relevant divalent cations modulate citrate recognition by the McpS chemoreceptor. J Mol Recognit 2011; 24 (02) 378-385
    Google Scholar
  • 24 van den Besselaar AM. Magnesium and manganese ions accelerate tissue factor-induced coagulation independently of factor IX. Blood Coagul Fibrinolysis 2002; 13 (01) 19-23
    Google Scholar
  • 25 Tokutake T, Baba H, Shimada Y. et al. Exogenous magnesium chloride reduces the activated partial thromboplastin times of lupus anticoagulant-positive patients. PLoS One 2016; 11 (06) e0157835
    Google Scholar
  • 26 Vadivel K, Agah S, Messer AS. et al. Structural and functional studies of γ-carboxyglutamic acid domains of factor VIIa and activated protein C: role of magnesium at physiological calcium. J Mol Biol 2013; 425 (11) 1961-1981
    Google Scholar
  • 27 Juutilainen A, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Similarity of the impact of type 1 and type 2 diabetes on cardiovascular mortality in middle-aged subjects. Diabetes Care 2008; 31 (04) 714-719
    Google Scholar