An Overview of Hemostasis

  • Akbar Dorgalaleh
  • Maryam Daneshi
  • Jamal Rashidpanah
  • Elaheh Roshani Yasaghi


Hemostasis is a physiological well-controlled complex process in the body in which the integrity of the circulatory system is maintained after vascular injury. This process has three main components including vascular system, cellular components, and noncellular components. These three components closely work together to keep the hemostasis system in the best situation.

Hemostasis is comprised of two arms: primary hemostasis and secondary hemostasis. Primary hemostasis using vascular endothelial cells and platelets leads to unstable hemostatic platelet plug formation. In secondary hemostasis, coagulation cascade activation results in stable fibrin clot formation. Overall, hemostasis causes bleeding to stop from the injured site. Natural anticoagulants are necessary to limit clot formation process at the injured site. The formed clot is required to be removed after healing process to restore blood flow. The fibrinolysis system is one of the most important requirements for clot removal. Procoagulant and anticoagulant elements interacted complicatedly to ensure an effective response to vascular injury that is limited to the injured site.


Primary hemostasis Secondary hemostasis Vascular system Endothelial Clot 


  1. 1.
    Osaki T, Ichinose A. Current views of activating and regulatory mechanisms of blood coagulation. Nihon rinsho Japanese. J Clin Med. 2014;72(7):1206–11.Google Scholar
  2. 2.
    Davie EW. A brief historical review of the waterfall/cascade of blood coagulation. J Biol Chem. 2003;278(51):50819–32.CrossRefPubMedGoogle Scholar
  3. 3.
    Butenas S, Mann K. Blood coagulation. Biochem Mosc. 2002;67(1):3–12.CrossRefGoogle Scholar
  4. 4.
    Kasirer-Friede A, Shattil SJ. Regulation of platelet adhesion receptors. In: Platelets in thrombotic and non-thrombotic disorders. Cham: Springer; 2017. p. 69–84.CrossRefGoogle Scholar
  5. 5.
    Feghhi S, Munday AD, Tooley WW, Rajsekar S, Fura AM, Kulman JD, et al. Glycoprotein Ib-IX-V complex transmits cytoskeletal forces that enhance platelet adhesion. Biophys J. 2016;111(3):601–8.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Bennett JS. Regulation of integrins in platelets. Peptide Sci. 2015;104(4):323–33.CrossRefGoogle Scholar
  7. 7.
    Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev. 2013;93(1):327–58.CrossRefPubMedGoogle Scholar
  8. 8.
    Gremmel T, Frelinger AL III, Michelson AD. Platelet physiology. Semin Thromb Hemost. 2016;42(3):191–204.CrossRefPubMedGoogle Scholar
  9. 9.
    Sorrentino S, Studt J-D, Medalia O, Sapra KT. Roll, adhere, spread and contract: structural mechanics of platelet function. Eur J Cell Biol. 2015;94(3):129–38.CrossRefPubMedGoogle Scholar
  10. 10.
    Goto S, Hasebe T, Takagi S. Platelets: small in size but essential in the regulation of vascular homeostasis–translation from basic science to clinical medicine. Circ J. 2015;79(9):1871–81.CrossRefPubMedGoogle Scholar
  11. 11.
    Coller B. αIIbβ3: structure and function. J Thromb Haemost. 2015;13(Suppl 1):S17–25.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bledzka K, Smyth SS, Plow EF. Integrin αIIbβ3. Circ Res. 2013;112(8):1189–200.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    López JA. The platelet glycoprotein Ib-IX-V complex. In: Gresele P, Kleiman N, Lopez J, Page C, editors. Platelets in thrombotic and non-thrombotic disorders. Cham: Springer; 2017. p. 85–97.CrossRefGoogle Scholar
  14. 14.
    Li R, Emsley J. The organizing principle of the platelet glycoprotein Ib–IX–V complex. J Thromb Haemost. 2013;11(4):605–14.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Madamanchi A, Santoro SA, Zutter MM. α2β1 integrin. In: I domain integrins. Cham: Springer; 2014. p. 41–60.Google Scholar
  16. 16.
    Arman M, Krauel K. Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis. J Thromb Haemost. 2015;13(6):893–908.CrossRefGoogle Scholar
  17. 17.
    Gawaz M, Vogel S, Pfannenberg C, Pichler B, Langer H, Bigalke B. Implications of glycoprotein VI for theranostics. Thromb Haemost. 2014;112(1):1–6.Google Scholar
  18. 18.
    Kunicki TJ. Platelet membrane glycoproteins and their function: an overview. Ann Hematol. 1989;59(1):30–4.Google Scholar
  19. 19.
    Nurden AT. Platelet membrane glycoproteins: a historical review. Semin Thromb Hemost. 2014;40:577–84.CrossRefPubMedGoogle Scholar
  20. 20.
    George JN. Platelet membrane glycoproteins. Cham: Springer; 2013.Google Scholar
  21. 21.
    Koseoglu S, Flaumenhaft R. Advances in platelet granule biology. Curr Opin Hematol. 2013;20(5):464–71.CrossRefPubMedGoogle Scholar
  22. 22.
    Heijnen H, Sluijs P. Platelet secretory behaviour: as diverse as the granules… or not? J Thromb Haemost. 2015;13(12):2141–51.CrossRefPubMedGoogle Scholar
  23. 23.
    Sadeghian MH, Keramati MR, Badiei Z, Ravarian M, Ayatollahi H, Rafatpanah H, et al. Alloimmunization among transfusion-dependent thalassemia patients. Asian J Transfusion Sci. 2009;3(2):95.CrossRefGoogle Scholar
  24. 24.
    Yadav S, Storrie B. The cellular basis of platelet secretion: emerging structure/function relationships. Platelets. 2017;28(2):108–18.CrossRefPubMedGoogle Scholar
  25. 25.
    Golebiewska EM, Poole AW. Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev. 2015;29(3):153–62.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Yau JW, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovasc Disord. 2015;15(1):130.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    van Hinsbergh VW. Endothelium—role in regulation of coagulation and inflammation. Semin Immunopathol. 2012;34:93–106.CrossRefPubMedGoogle Scholar
  28. 28.
    Monahan-Earley R, Dvorak AM, Aird WC. Evolutionary origins of the blood vascular system and endothelium. J Thromb Haemost. 2013;11(s1):46–66.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Dekker RJ, van Thienen JV, Rohlena J, de Jager SC, Elderkamp YW, Seppen J, et al. Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am J Pathol. 2005;167(2):609–18.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Aird WC. Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res. 2007;100(2):174–90.CrossRefPubMedGoogle Scholar
  31. 31.
    Bode M, Mackman N. Protective and pathological roles of tissue factor in the heart. Hamostaseologie. 2015;35(1):37–46.CrossRefPubMedGoogle Scholar
  32. 32.
    Borissoff JI, Spronk HM, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med. 2011;364(18):1746–60.CrossRefPubMedGoogle Scholar
  33. 33.
    Schousboe I. Binding of activated Factor XII to endothelial cells affects its inactivation by the C1-esterase inhibitor. FEBS J. 2003;270(1):111–8.Google Scholar
  34. 34.
    Do H, Healey JF, Waller EK, Lollar P. Expression of factor VIII by murine liver sinusoidal endothelial cells. J Biol Chem. 1999;274(28):19587–92.CrossRefPubMedGoogle Scholar
  35. 35.
    Dubois C, Panicot-Dubois L, Gainor JF, Furie BC, Furie B. Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model. J Clin Investig. 2007;117(4):953.CrossRefPubMedGoogle Scholar
  36. 36.
    Esmon CT, Esmon NL. The link between vascular features and thrombosis. Annu Rev Physiol. 2011;73:503–14.CrossRefPubMedGoogle Scholar
  37. 37.
    Wood JP, Ellery PE, Maroney SA, Mast AE. Biology of tissue factor pathway inhibitor. Blood. 2014;123(19):2934–43.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Dahm A, van Hylckama Vlieg A, Bendz B, Rosendaal F, Bertina RM, Sandset PM. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis. Blood. 2003;101(11):4387–92.CrossRefPubMedGoogle Scholar
  39. 39.
    Collen D, Lijnen HR. The tissue-type plasminogen activator story. Arterioscler Thromb Vasc Biol. 2009;29(8):1151–5.CrossRefPubMedGoogle Scholar
  40. 40.
    Chung DW, Fujikawa K. Processing of von Willebrand factor by ADAMTS-13. Biochemistry. 2002;41(37):11065–70.CrossRefPubMedGoogle Scholar
  41. 41.
    Petraglia AL, Marky AH, Walker C, Thiyagarajan M, Zlokovic BV. Activated protein C is neuroprotective and mediates new blood vessel formation and neurogenesis after controlled cortical impact. Neurosurgery. 2010;66(1):165–72.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Adams RL, Bird RJ. coagulation cascade and therapeutics update: relevance to nephrology. Part 1: overview of coagulation, thrombophilias and history of anticoagulants. Nephrology. 2009;14(5):462–70.CrossRefPubMedGoogle Scholar
  43. 43.
    Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth. 2014;58(5):515.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Mann KG, Brummel-Ziedins K, Orfeo T, Butenas S. Models of blood coagulation. Blood Cell Mol Dis. 2006;36(2):108–17.CrossRefGoogle Scholar
  45. 45.
    Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica. 2000;85(9):967–72.PubMedGoogle Scholar
  46. 46.
    Mann KG, Butenas S, Brummel K. The dynamics of thrombin formation. Arterioscler Thromb Vasc Biol. 2003;23(1):17–25.CrossRefPubMedGoogle Scholar
  47. 47.
    Lasne D, Jude B, Susen S. From normal to pathological hemostasis. Can J Anesth. 2006;53(2):S2–S11.CrossRefPubMedGoogle Scholar
  48. 48.
    Pike RN, Buckle AM, Le Bonniec BF, Church FC. Control of the coagulation system by serpins. FEBS J. 2005;272(19):4842–51.CrossRefPubMedGoogle Scholar
  49. 49.
    Rigby AC, Grant MA. Protein S: a conduit between anticoagulation and inflammation. Crit Care Med. 2004;32(5):S336–41.CrossRefPubMedGoogle Scholar
  50. 50.
    Dahm A, Sandset P, Rosendaal F. The association between protein S levels and anticoagulant activity of tissue factor pathway inhibitor type 1. J Thromb Haemost. 2008;6(2):393–5.CrossRefPubMedGoogle Scholar
  51. 51.
    Corral J, González-Conejero R, Hernández-Espinosa D, Vicente V. Protein Z/Z-dependent protease inhibitor (PZ/ZPI) anticoagulant system and thrombosis. Br J Haematol. 2007;137(2):99–108.CrossRefPubMedGoogle Scholar
  52. 52.
    Rijken D, Lijnen H. New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost. 2009;7(1):4–13.CrossRefPubMedGoogle Scholar
  53. 53.
    Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost. 2005;93(4):631–40.PubMedGoogle Scholar
  54. 54.
    Ezihe-Ejiofor JA, Hutchinson N. Anticlotting mechanisms 1: physiology and pathology. Contin Edu Anaesth Crit Care Pain. 2013;13(3):87–92.CrossRefGoogle Scholar
  55. 55.
    Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev. 2015;29(1):17–24.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Akbar Dorgalaleh
    • 1
  • Maryam Daneshi
    • 1
  • Jamal Rashidpanah
    • 2
  • Elaheh Roshani Yasaghi
    • 3
  1. 1.Department of Hematology and Blood TransfusionSchool of Allied Medicine, Iran University of Medical SciencesTehranIran
  2. 2.Tehran Heart CenterTehranIran
  3. 3.TehranIran

Personalised recommendations