Polyphosphate modulates blood coagulation and fibrinolysis

Stephanie A Smith, Nicola Jane Mutch, Deepak Baskar, Peter Rohloff, Roberto Docampo, James H Morrissey

Research output: Contribution to journalArticle

334 Citations (Scopus)

Abstract

Inorganic polyphosphate is an abundant component of acidocalcisomes of bacteria and unicellular eukaryotes. Human platelet dense granules strongly resemble acidocalcisomes, and we recently showed that they contain substantial amounts of polyphosphate, which is secreted upon platelet activation. We now report that polyphosphate is a potent hemostatic regulator, accelerating blood clotting by activating the contact pathway and promoting the activation of factor V, which in turn results in abrogation of the function of the natural anticoagulant protein, tissue factor pathway inhibitor. Polyphosphate was also found to delay clot lysis by enhancing a natural antifibrinolytic agent, thrombin-activatable fibrinolysis inhibitor. Polyphosphate is unstable in blood or plasma, owing to the presence of phosphatases. We propose that polyphosphate released from platelets or microorganisms initially promotes clot formation and stability; subsequent degradation of polyphosphate by blood phosphatases fosters inhibition of clotting and activation of fibrinolysis during wound healing.
Original languageEnglish
Pages (from-to)903-908
Number of pages6
JournalPNAS
Volume103
Issue number4
DOIs
Publication statusPublished - 24 Jan 2006

Fingerprint

Polyphosphates
Blood Coagulation
Fibrinolysis
Phosphoric Monoester Hydrolases
Blood Platelets
Carboxypeptidase B2
Antifibrinolytic Agents
Factor V
Platelet Activation
Hemostatics
Eukaryota
Wound Healing
Anticoagulants
Bacteria

Keywords

  • Anticoagulants
  • Blood Coagulation
  • Blood Coagulation Factors
  • Blood Platelets
  • Carboxypeptidase U
  • Cytoplasmic Granules
  • Factor V
  • Fibrinolysis
  • Humans
  • Lipoproteins
  • Polyphosphates
  • Thrombin
  • Time Factors
  • Wound Healing

Cite this

Smith, S. A., Mutch, N. J., Baskar, D., Rohloff, P., Docampo, R., & Morrissey, J. H. (2006). Polyphosphate modulates blood coagulation and fibrinolysis. PNAS, 103(4), 903-908. https://doi.org/10.1073/pnas.0507195103

Polyphosphate modulates blood coagulation and fibrinolysis. / Smith, Stephanie A; Mutch, Nicola Jane; Baskar, Deepak; Rohloff, Peter; Docampo, Roberto; Morrissey, James H.

In: PNAS, Vol. 103, No. 4, 24.01.2006, p. 903-908.

Research output: Contribution to journalArticle

Smith, SA, Mutch, NJ, Baskar, D, Rohloff, P, Docampo, R & Morrissey, JH 2006, 'Polyphosphate modulates blood coagulation and fibrinolysis', PNAS, vol. 103, no. 4, pp. 903-908. https://doi.org/10.1073/pnas.0507195103
Smith SA, Mutch NJ, Baskar D, Rohloff P, Docampo R, Morrissey JH. Polyphosphate modulates blood coagulation and fibrinolysis. PNAS. 2006 Jan 24;103(4):903-908. https://doi.org/10.1073/pnas.0507195103
Smith, Stephanie A ; Mutch, Nicola Jane ; Baskar, Deepak ; Rohloff, Peter ; Docampo, Roberto ; Morrissey, James H. / Polyphosphate modulates blood coagulation and fibrinolysis. In: PNAS. 2006 ; Vol. 103, No. 4. pp. 903-908.
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KW - Anticoagulants

KW - Blood Coagulation

KW - Blood Coagulation Factors

KW - Blood Platelets

KW - Carboxypeptidase U

KW - Cytoplasmic Granules

KW - Factor V

KW - Fibrinolysis

KW - Humans

KW - Lipoproteins

KW - Polyphosphates

KW - Thrombin

KW - Time Factors

KW - Wound Healing

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