Skip to main content
SpringerLink
Log in

Role of Zinc in Hemostasis: A Review

  • Review
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Zinc is a multi-functional element that is found in almost 300 enzymes where it performs catalytic, co-catalytic, and/or structural functions. In 1982, Gordon et al. (Am J Clin Ntr 35:849–857, 1982) found that a low zinc diet caused poor platelet aggregation and increased bleeding tendency in adult males. This fact drew interest to the role of zinc in blood clotting. It has been shown that hyperzincemia predisposes to increased coagulability, and hypozincemia to poor platelet aggregation and increased bleeding time. The blood clotting disturbances can be regressed by appropriate zinc intake management. Considering the importance of zinc as an essential element, its participation in regulation of the equilibrium between pro- and anti-thrombotic factors originating in platelets and endothelium prompted further investigations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gordon PR, Woodruff CW, Anderson HL, O’Dell BL (1982) Effects of acute zinc deprivation on plasma zinc and platelet aggregation in adult males. Am J Clin Nutr 35:849–857

    Google Scholar 

  2. Vallee BL, Falchuk KH (1993) The biochemical basis of zinc physiology. Physiol Rev 73:79–87

    PubMed  CAS  Google Scholar 

  3. Kokot F, Tatoń J (1991) In: Kokota F (ed) Zaburzenia przemiany materii w “Chorobach Wewnętrznych” pod red. PZWL, Warszawa, p 670

  4. Holtmeier HJ, Kuhn M, Rummel K (1976) Zink ein lebenswichtiges Mineral. Wissenschaftliche Verlagsgeselschaft MbH, Stuttgart, p 13

    Google Scholar 

  5. Turner AJ, Brown CD, Carson JA, Barens K (2000) The neprilysin family in health and disease. Adv Exp Med Biol 477:229–240

    Article  PubMed  CAS  Google Scholar 

  6. Kulikowska E, Moniuszko-Jakoniuk J, Miniuk K (1991) Rola cynku w procesach fizjologicznych i patologicznych organizmu. Pol Tyg Lek 46:471–475

    Google Scholar 

  7. Cousins RJ (1986) Toward a molecular understanding of zinc metabolism. Clin Physiol Biochem 4:20–30

    PubMed  CAS  Google Scholar 

  8. O’Dell BL (2000) Role of zinc in plasma membrane function. J Nutr 130:1432S–1436S

    PubMed  CAS  Google Scholar 

  9. Avery RA, Bettger WJ (1992) Zinc deficiency alters the protein composition of the membrane skeleton but not the extractability or oligomeric form of spectrin in rat erythrocyte membranes. J Nutr 122:428–433

    PubMed  CAS  Google Scholar 

  10. Bettger WJ, O`Dell BL (1981) A critical physiological role of zinc in the structure and function of biomembranes. Life Sci 28:1425–1438

    Article  PubMed  CAS  Google Scholar 

  11. Carvalho A (1972) Binding and release of cations by sarcoplasmic reticulum before and after removal of lipids. Eur J Biochem 27:491–496

    Article  PubMed  CAS  Google Scholar 

  12. Driscoll ER, Bettger WJ (1992) Zinc deficiency in the rat alters the lipid composition of the erythrocyte membrane Triton shell. Lipids 27:972–977

    Article  PubMed  CAS  Google Scholar 

  13. Harrison NL, Radke HK, Tamkun MM, Lovinger DM (1993) Modulation of gating of cloned rat and human K+ channels by micromolar Zn+2. Mol Pharmacol 43:482–490

    PubMed  CAS  Google Scholar 

  14. a. Heinemann SH, Struhnar W, Molecular structure of potassium and sodium channels and their structure-function correlation, p 109–112, b. Nilins B, Droogmans G, Ion channels of endothelial cells, p 964, in Physiology and pathophysiology of the heart, Sparelakis N (1995) 3rd ed., Kluwer, Dortrecht

  15. Maccara IG (1985) Oncogenesis, ions and phospholipids. Am J Physiol 248:C3–C8

    Google Scholar 

  16. Dorup I, Clausen T (1991) Effects of magnesium and zinc deficiencies on growth and protein synthesis in skeletal muscle and the heart. Br J Nutr 66:493–504

    Article  PubMed  CAS  Google Scholar 

  17. Csermely P, Somogyi J (1989) Zinc as a possible mediator of signal transduction in T lymphocytes. Acta Physiol Hung 74:195–199

    PubMed  CAS  Google Scholar 

  18. Csermely P, Sandor P, Radics L, Somogyi J (1989) Zinc forms complexes with higher kinetical stability than calcium, 5-F-BAPTA as a good example. Biochem Biophys Res Commun 165:838–843

    Article  PubMed  CAS  Google Scholar 

  19. Girchev R, Tzachev K (1998) Metabolism and homeostasis of zinc and copper. Acta Physiol Pol 39(supl. 32):103–112

    Google Scholar 

  20. McMaster D, McCrum E, Patterson CC (1992) Serum copper and zinc in random samples of the population of Northen Ireland. Am J Clin Nutr 56:440–445

    PubMed  CAS  Google Scholar 

  21. Gorodetsky R, Mou X, Blankenfeld A, Marx G (1993) Platelet multielemental composition, lability and subcellular localization. Am J Hematol 42:278–283

    Article  PubMed  CAS  Google Scholar 

  22. Marx G, Eldor A (1985) The procoagulant effect of zinc on fibrin clot formation. Am J Hematol 19:151–159

    Article  PubMed  CAS  Google Scholar 

  23. Hughes S, NutrDiet M, Samman S (2006) The effect of zinc supplementation in humans on plasma lipids, antioxidant status and thrombogenesis. J Am Coll Nutr 25:285–291

    PubMed  CAS  Google Scholar 

  24. Bernardo MM, Day DE, Olson ST, Halvorson HR, Shore JD (1993) Surface-independent acceleration of factor XII activation by zinc ions. I. Kinetic characterization of the metal ion rate enhancement. J Biol Chem 268:12468–12476

    PubMed  CAS  Google Scholar 

  25. Bernardo MM, Day DE, Olson ST, Halvorson HR, Shore JD (1993) Surface-independent acceleration of factor XII activation by zinc ions. II. Direct binding and fluorescence studies. J Biol Chem 268:12477–12483

    PubMed  CAS  Google Scholar 

  26. Schousboe I (1990) The inositol-phospholipid-accelerated activation of prekallikrein by activated factor XII at physiological ionic strength zinc ions and high-Mr kininogen. Eur J Bichem 193:495–499

    Article  CAS  Google Scholar 

  27. Shimada T, Kato H, Iwanaga S (1987) Accelerating effect of zinc ions on the surface-mediated activation of factor XII and prekallikrein. J Biochem 102:913–921

    PubMed  CAS  Google Scholar 

  28. Shore JD, Day DE, Bock PE, Olson ST (1987) Acceleration of surface-dependent autocatalytic activation of blood coagulation factor XII by divalent metal ions. Biochemistry 26:2250–2258

    Article  PubMed  CAS  Google Scholar 

  29. Reddigari SR, Shibayama Y, Brunnee T, Kaplan AP (1993) Human Hageman factor (Factor XII) and high molecular weight kininogen compete for the same binding site on human umbilical vein endothelial cells. J Biol Chem 268:11982–11987

    PubMed  CAS  Google Scholar 

  30. Silverberg M, Diehl SV (1987) The autoactivation of factor XII (Hageman factor) induced by low-Mr heparin and dextran sulphate. The effect of the Mr of the activating polyanion. Biochem J 248:715–720

    PubMed  CAS  Google Scholar 

  31. Samuel M, Pixley RA, Villanueva MA, Colman RW, Vullanueva GB (1992) Human factor XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and ultraviolet difference spectroscopic studies. J Biol Chem 267:19691–19697

    PubMed  CAS  Google Scholar 

  32. Petersen LC, Olsen OH, Nielsen LS, Freskgard P, Persson E (2000) Binding of Zn2+ to a Ca2+ loop alloserically attenuates the activity of factor VIIa and reduces its affinity for tissue factor. Protein Sci 9:859–866

    Article  PubMed  CAS  Google Scholar 

  33. Gailani D, Broze GJ Jr (1991) Factor XI activation in a revised model of blood coagulation. Science 253:909–912

    Article  PubMed  CAS  Google Scholar 

  34. Baglia FA, Badellino KO, Ho DH, Dasari VR, Walsh PN (2000) A binding site for the kringle II domain of prothrombin in the apple 1 domain of factor XI. J Biol Chem 275:31954–31962

    Article  PubMed  CAS  Google Scholar 

  35. Baglia FA, Gailani D, Lopez JA, Walsh PN (2004) Identification of a binding site for glycoprotein Ibα in Apple 3 domain of factor XI. J Biol Chem 279:24270–45476

    Google Scholar 

  36. Greengard JS, Heeb MJ, Ersdal E, Walsh PN, Griffin JH (1986) Binding of coagulation factor XI to washed human platelets. Biochem 25:3884–3890

    Article  CAS  Google Scholar 

  37. Baird TR, Walsh PN (2002) Activated platelets but not endothelial cell participate in the initiation of the consolidation phase of blood coagulation. J Biol Chem 277:28498–24503

    Article  PubMed  CAS  Google Scholar 

  38. Van Nostrand WE (1995) Zinc (II) selectively enhances the inhibition of coagulation factor XIa by protease nexin-2/amyloid beta-protein precursor. Thromb Res 78:43–53

    Article  PubMed  Google Scholar 

  39. Mahdi F, Shariat-Madar Z, Schmaier AH (2003) The relative priority of prekallikrein and factors XI/XIa assembly on cultured endothelial cells. J Biol Chem 278:43983–43990

    Article  PubMed  CAS  Google Scholar 

  40. Rojkjaer R, Schmaier AH (1999) Activation of the plasma kallikrein/kinin system on endothelial cell membranes. Immunopharmacology 43:109–114 (Abstract)

    Article  PubMed  CAS  Google Scholar 

  41. Kluszynski BA, Kim C, Faulk WP (1997) Zinc as a cofactor for heparin neutralization by histidine –rich glycoprotein. J Biol Chem 272:13541–13547

    Article  PubMed  CAS  Google Scholar 

  42. Marx G (1988) Divalent cations induce protofibril gelation. Am J Hekamtol 27:104–109

    Article  CAS  Google Scholar 

  43. Hopmeier P, Halbmayer M, Fischer M, Marx G (1990) Zinc modulates thrombin adsorption to fibrin. Thromb Res 58:293–301

    Article  PubMed  CAS  Google Scholar 

  44. Dugan TA, Yang VW-C, McQuillan DJ, Höök M (2006) Decorin modulates fibrin assembly and structure. J Biol Chem 281:38208–38216

    Article  PubMed  CAS  Google Scholar 

  45. O’Dell BL (2000) Role of zinc in plasma membrane function. J Nutr 130:1432S–1436S

    PubMed  CAS  Google Scholar 

  46. Kimura Y, Hart A, Hirashima M et al (2002) Zinc finger protein, Hzf, is required for megakaryocyte development and hemostasis. J Exp Med 195:941–952

    Article  PubMed  CAS  Google Scholar 

  47. Husain SS (1993) Fibrin affinity of urokinase-type plasminogen activator. Evidence that Zn2+ mediates strong and specific interaction of single-chain urokinase with fibrin. J Biol Chem 268:8574–8579

    PubMed  CAS  Google Scholar 

  48. Jones AL, Hulett MD, Altin JG, Hogg Ph, Parish ChR (2004) Plasminogen is tethered with high affinity to the cell surface by the plasma protein, histidine-rich glycoprotein. J Biol Chem 279:38267–38276

    Article  PubMed  CAS  Google Scholar 

  49. Lijnen HR (2001) Elements of the fibrinolytic system. Ann N Y Acad Sci 936:226–236

    Article  PubMed  CAS  Google Scholar 

  50. Marx PF, Bouma BN, Meijers JC (2002) Role of zinc ions in activation and inactivation of thrombin-activatable fibrinolysis inhibitor. Biochemistry 41:1211–1216

    Article  PubMed  CAS  Google Scholar 

  51. Mahdi F, Madar ZS, Figueroa CD, Schmaier AH (2002) Factor XII interacts with the multiprotein assembly of urokinase plasminogen activator receptor, gC1qR, and cytoceratin 1 on endothelial cell membranes. Blood 99:3585–3596

    Article  PubMed  CAS  Google Scholar 

  52. Schousboe I (1997) Factor XIIa activation of plasminogen is enhanced by contact activating surfaces and Zn2+. Blood Coagul Fibrinolysis 8:97–104

    Article  PubMed  CAS  Google Scholar 

  53. Kaji T (2004) Cell biology of heavy metal toxicity in vascular tissue. Yakugaku Zasshi 124:113–120 (Abstract)

    Article  PubMed  CAS  Google Scholar 

  54. Tao J, Yang Z, Wang JM, Luo CF, Tang AL, Dong GY, Ma H (2007) Shear stress increases Cu/Zn SOD activity and mRNA expression in human endothelial progenitor cells. J Hum Hypertens 21:353–358

    Article  PubMed  CAS  Google Scholar 

  55. Inoue N, Ramasamy S, Fukai T, Nerem RM, Harrisom DG (1996) Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells. Circ Res 79:32–37

    PubMed  CAS  Google Scholar 

  56. Gracia CE, Kdcoyne CM, Cardillo C, Cannon RO 3rd, Quyyumi AA, Panza JA (1995) Effect of copper-zinc superoxide dismutase on endothelium-dependent vasodilation in patients with essential hypertension. Hypertension 26:863–868

    Google Scholar 

  57. Sato M, Yanagisawa H, Nojima Y, Tamura J, Wada O (2002) Zn deficiency aggravates hypertension in spontaneously hypertensive rats: possible role of Cu/Zn-superoxide dismutase. Clin Exp Hypertens 24:355–370

    Article  PubMed  CAS  Google Scholar 

  58. Cebeci SA, Kocaturk PA, Kavas GO (2002) Hypertension: does impaired endothelium-dependent relaxation affect superoxide scavenging? Biol Trace Elem Res 90:239–249

    Article  PubMed  CAS  Google Scholar 

  59. Sato M, Kurihara N, Moridaira K, Sakamoto H, Tamura J, Wada O, Yanagisawa H (2003) Dietary Zn deficiency does not influence systemic blood pressure and vascular nitric oxide signaling in normotensive rats. Biol Trace Elem Res 91:157–172

    Article  PubMed  CAS  Google Scholar 

  60. Yanagisawa H, Sato M, Nodera M, Wada O (2004) Excessive zinc intake elevates systemic blood pressure levels in normotensive rats—potential role of superoxide-induced oxidative stress. J Hypertens 22:543–550

    Article  PubMed  CAS  Google Scholar 

  61. Tsai HM (2003) Shear stress and von Willebrand factor in health and disease. Semin Thromb Hemost 29:479–488

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Physical Education and Physiotherapy, Institute of Technology, Opole, Prószkowska Street 76, 45-758, Opole, Poland

    Sławomir Tubek & Iwona Tubek

  2. Department of Internal Diseases, University Hospital of Collegium Medicum, Jagiellonian University, Kraków, Poland

    Piotr Grzanka

Authors
  1. Sławomir Tubek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Piotr Grzanka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Iwona Tubek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sławomir Tubek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tubek, S., Grzanka, P. & Tubek, I. Role of Zinc in Hemostasis: A Review. Biol Trace Elem Res 121, 1–8 (2008). https://doi.org/10.1007/s12011-007-8038-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-007-8038-y

Keywords

Search

Navigation