Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.7)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 9, September, p. 1051–1056

doi: 10.17219/acem/125430

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Platelet polyphosphate level is elevated in patients with chronic primary thrombocytopenia: A preliminary study

Ewa Żurawska-Płaksej1,A,C,D,E,F, Wiktor Kuliczkowski2,A,C,D,F, Bożena Karolko2,B,C,F, Magdalena Cielecka-Prynda2,B,E,F, Jakub Dębski2,B,C,F, Konrad Kaaz2,B,E,F, Andrzej Mysiak2,A,E,F, Tomasz Wróbel3,B,E,F, Maria Podolak-Dawidziak3,C,D,E,F, Lidia Usnarska-Zubkiewicz1,A,E,F

1 Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Poland

2 Department and Clinic of Cardiology, Wroclaw Medical University, Poland

3 Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Poland

Abstract

Background. Platelets are key players in hemostasis. These blood cells contain different types of granules. Recently, there has been a growing interest in the role of inorganic polyphosphate (polyP) structures stored in dense granules of platelets and secreted during platelet activation.
Objectives. To measure platelet polyP levels in patients with thrombocytopenia and thrombocythemia, and to examine the relationship of this indicator with platelet aggregation.
Material and Methods. The study included 36 patients with hematological disorders (26 with primary chronic thrombocytopenia and 10 with essential thrombocythemia (ET)) and 40 healthy subjects. Platelet reactivity was measured using whole blood impedance aggregometry. The polyP levels were isolated from lysed platelets, which were obtained from citrated platelet-rich plasma. The procedure included inactivating endogenous phosphatases, removing phosphate units derived from DNA and proteins, and finally hydrolyzing them into monophosphate units. A colorimetric assay using malachite green and ammonium molybdate was performed in order to quantify polyP levels.
Results. The polyP concentrations were significantly higher in the patients with thrombocytopenia than in the patients with thrombocythemia or the controls. The polyP level was not correlated with the level of aggregation.
Conclusion. The higher polyP levels observed in the patients with low platelet counts may indicate the existence of a compensatory mechanism that prevents excessive bleeding in such patients. Our study provides evidence of an essential role of polyP in platelet function and the coagulation process.

Key words

coagulation, platelets, thrombocytopenia, essential thrombocythemia, platelet polyphosphate

References (19)

  1. Travers RJ, Smith SA, Morrissey JH. Polyphosphate, platelets, and coagulation. Int J Lab Hematol. 2015;37(1):31–35.
  2. Morrissey JH, Smith SA. Polyphosphate as modulator of hemostasis, thrombosis, and inflammation. J Thromb Haemost. 2015;13(Suppl 1):S92–S97.
  3. Mutch NJ. Polyphosphate as a haemostatic modulator. Biochem Soc Trans. 2016;44(1):18–24.
  4. Morrissey JH. Contributions of platelet polyphosphate to hemostasis and thrombosis. In: Saba HI, Roberts HR, eds. Hemostasis and Thrombosis. Oxford, UK: Wiley Blackwell UK; 2014:2360–2453.
  5. Mailer RKW, Hänel L, Allende M, Renné T. Polyphosphate as a target for interference with inflammation and thrombosis. Front Med (Lausanne). 2019;6:1–10.
  6. Montilla M, Hernandez-Ruiz L, Garcia-Cozar FJ, Alvarez-Laderas I, Rodríguez-Martorell J, Ruiz FA. Polyphosphate binds to human von Willebrand factor in vivo and modulates its interaction with glycoprotein Ib. J Thromb Haemost. 2012;10(11):2315–2323.
  7. Nickel KF, Ronquist G, Langer F, et al. The polyphosphate-factor XII pathway drives coagulation in prostate cancer-associated thrombosis. Blood. 2015;126(11):1379–1389.
  8. Verhoef JJF, Barendrecht AD, Nickel KF, et al. Polyphosphate nanoparticles on the platelet surface trigger contact system activation. Blood. 2017;129(12):1707–1717.
  9. Schlagenhauf A, Pohl S, Haidl H, Leschnik B, Gallistl S, Muntean W. Non-enzymatic quantification of polyphosphate levels in platelet lysates and releasates. J Pharm Biomed Anal. 2016;131:1–5.
  10. Smith SA, Morrissey JH. Polyphosphate enhances fibrin clot structure. Blood. 2008;112(7):2810–2816.
  11. Mitchell JL, Lionikiene AS, Georgiev G, et al. Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity. Blood. 2016;128(24):2834–2845.
  12. Whyte CS, Chernysh IN, Domingues MM, et al. Polyphosphate delays fibrin polymerisation and alters the mechanical properties of the fibrin network. Thromb Haemost. 2016;116(5):897–903.
  13. Mutch NJ, Engel R, Uitte de Willige S, Philippou H, Ariëns RAS. Polyphosphate modifies the fibrin network and down-regulates fibrinolysis by attenuating binding of tPA and plasminogen to fibrin. Blood. 2010;115(19):3980–3988.
  14. Duchemin J, Ugo V, Ianotto J-C, Lecucq L, Mercier B, Abgrall J-F. Increased circulating procoagulant activity and thrombin generation in patients with myeloproliferative neoplasms. Thromb Res. 2010;126(3):238–242.
  15. Choi SH, Smith SA, Morrissey JH. Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood. 2011;118(26):6963–6970.
  16. Wood JP, Petersen HH, Yu B, Wu X, Hilden I, Mast AE. TFPIα interacts with FVa and FXa to inhibit prothrombinase during the initiation of coagulation. Blood Adv. 2017;1(27):2692–2702.
  17. Monroe DM, Hoffman M, Robert HR. Platelets and thrombin generation. Atherosc Thromb Vasc Biol. 2002;22(9):1381–1389.
  18. Hernández-Ruiz L, Sáez-Benito A, Pujol-Moix N, Rodríguez-Martorell J, Ruiz FA. Platelet inorganic polyphosphate decreases in patients with delta storage pool disease. J Thromb Haemost. 2009;7(2):361–363.
  19. Melazzini F, Zaninetti C, Balduini CL. Bleeding is not the main clinical issue in many patients with inherited thrombocytopaenias. Haemophilia. 2017;23(5):673–681.