Annals of Hematology

, Volume 92, Issue 12, pp 1633–1639 | Cite as

Global coagulation in myeloproliferative neoplasms

  • Armando Tripodi
  • Veena Chantarangkul
  • Francesca Gianniello
  • Marigrazia Clerici
  • Laura Lemma
  • Lidia Padovan
  • Loredana Gatti
  • Pier Mannuccio Mannucci
  • Flora Peyvandi
Original Article

Abstract

In spite of their recognized risk of thrombosis, patients with myeloproliferative neoplasms (MPN) show little or no abnormalities of traditional coagulation tests, perhaps because these are unable to represent the balance between pro- and anticoagulants nor the effect of platelets and blood cells. We investigated whether global tests such as thrombin generation in platelet-rich plasma (PRP) or thromboelastometry in whole blood were able to detect signs of procoagulant imbalance in MPN. The endogenous thrombin potential (ETP) of 111 patients and 89 controls was measured in PRP with platelet count adjusted to the original patient- or control-count. Testing was performed with and without thrombomodulin (the physiological protein C activator) and results were expressed as ETP ratios (with/without thrombomodulin). High ETP ratios reflect resistance to thrombomodulin and were taken as indexes of procoagulant imbalance. Patients were also investigated by thromboelastometry that provides such parameters as the clot formation time (CFT) and maximal clot firmness (MCF). Short CFT or high MCF were taken as indexes of procoagulant imbalance. ETP ratios were higher in patients than in controls and were directly correlated with platelet counts and inversely with the plasma levels of free protein S, protein C and antithrombin. Patients on hydroxyurea had lower ETP ratios than those on other treatments. CFT was shorter and MCF was greater in patients than controls; CFT and MCF were correlated with platelet counts. In conclusion, patients with MPN display a procoagulant imbalance detectable by thrombin generation and thromboelastometry. These tests might be useful in the frame of clinical trials to assess their association with the occurrence of thrombosis and with the effect of therapeutic strategies in MPN.

Keywords

Thrombin generation Thromboelastometry Essential thrombocythemia Polycythemia vera Thrombosis 

References

  1. 1.
    Landolfi R, Cipriani MC, Novarese L (2006) Thrombosis and bleeding in polycythemia vera and essential thrombocythemia: pathogenetic mechanisms and prevention. Best Pract Res Clin Haematol 19:617–633PubMedCrossRefGoogle Scholar
  2. 2.
    Vannucchi AM (2011) Management of myelofibrosis. Hematol Am Soc Hematol Educ Program 2011:222–230CrossRefGoogle Scholar
  3. 3.
    Barbui T (2011) How to manage thrombosis in myeloproliferative neoplasms. Curr Opin Oncol 23:654–658PubMedCrossRefGoogle Scholar
  4. 4.
    Falanga A, Marchetti M, Vignoli A, Balducci D, Barbui T (2005) Leukocyte–platelet interaction in patients with essential thrombocythemia and polycythemia vera. Exp Hematol 33:523–530PubMedCrossRefGoogle Scholar
  5. 5.
    Tripodi A, Chantarangkul V, Mannucci PM (2009) Acquired coagulation disorders: revisited using global coagulation/anticoagulation testing. Br J Haematol 147:77–82PubMedCrossRefGoogle Scholar
  6. 6.
    Mann KG, Brummel K, Butenas S (2003) What is all that thrombin for? J Thromb Haemost 1:1504–1514PubMedCrossRefGoogle Scholar
  7. 7.
    Tripodi A, Mannucci PM (2011) The coagulopathy of chronic liver disease. N Engl J Med 365:147–156PubMedCrossRefGoogle Scholar
  8. 8.
    Tripodi A, Cappellini MD, Chantarangkul V, Padovan L, Fasulo MR, Marcon A et al (2009) Hypercoagulability in splenectomized thalassemic patients detected by whole-blood thromboelastometry, but not by thrombin generation in platelet-poor plasma. Haematologica 94:1520–1527PubMedCrossRefGoogle Scholar
  9. 9.
    Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA et al (2007) Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 110:1092–1097PubMedCrossRefGoogle Scholar
  10. 10.
    Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R et al (2003) Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 33:4–15PubMedCrossRefGoogle Scholar
  11. 11.
    Chantarangkul V, Clerici M, Bressi C, Giesen PL, Tripodi A (2003) Thrombin generation assessed as endogenous thrombin potential in patients with hyper- or hypo-coagulability. Haematologica 88:547–554PubMedGoogle Scholar
  12. 12.
    Lang T, Bauters A, Braun SL, Pötzsch B, von Pape KW, Kolde HJ et al (2005) Multi-centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagul Fibrinolysis 16:301–310PubMedCrossRefGoogle Scholar
  13. 13.
    Marchetti M, Castoldi E, Spronk HM, van Oerle R, Balducci D, Barbui T et al (2008) Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera. Blood 112:4061–4068PubMedCrossRefGoogle Scholar
  14. 14.
    Tripodi A, Legnani C, Chantarangkul V, Cosmi B, Palareti G, Mannucci PM (2008) High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost 6:1327–1333PubMedCrossRefGoogle Scholar
  15. 15.
    Tripodi A, Anstee QM, Sogaard KK, Primignani M, Valla DC (2011) Hypercoagulability in cirrhosis: causes and consequences. J Thromb Haemost 9:1713–1723PubMedCrossRefGoogle Scholar
  16. 16.
    Ruggeri M, Gisslinger H, Tosetto A, Rintelen C, Mannhalter C, Pabinger I et al (2002) Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia. Am J Hematol 71:1–6PubMedCrossRefGoogle Scholar
  17. 17.
    Amitrano L, Guardascione MA, Ames PR, Margaglione M, Antinolfi I, Iannaccone L et al (2003) Thrombophilic genotypes, natural anticoagulants, and plasma homocysteine in myeloproliferative disorders: relationship with splanchnic vein thrombosis and arterial disease. Am J Hematol 72:75–81PubMedCrossRefGoogle Scholar
  18. 18.
    Kornblihtt LI, Heller PG, Correa G, Castañón M, Genoud V, Vassallu P et al (2003) Associated thrombophilic defects in essential thrombocythaemia: their relationship with clinical manifestations. Thromb Res 112:131–135PubMedCrossRefGoogle Scholar
  19. 19.
    Tan X, Shi J, Fu Y, Gao C, Yang X, Li J et al (2013) Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation. Thromb Haemost 109:1025–1032PubMedCrossRefGoogle Scholar
  20. 20.
    Panova-Noeva M, Marchetti M, Spronk HM, Russo L, Diani E, Finazzi G et al (2011) Platelet-induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera. Am J Hematol 86:337–342PubMedCrossRefGoogle Scholar
  21. 21.
    Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F et al (1995) Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332:1132–1136PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Armando Tripodi
    • 1
    • 3
  • Veena Chantarangkul
    • 1
    • 3
  • Francesca Gianniello
    • 1
    • 3
  • Marigrazia Clerici
    • 1
    • 3
  • Laura Lemma
    • 1
    • 3
  • Lidia Padovan
    • 1
    • 3
  • Loredana Gatti
    • 1
    • 3
  • Pier Mannuccio Mannucci
    • 2
    • 3
  • Flora Peyvandi
    • 1
    • 3
  1. 1.Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community HealthUniversità degli Studi di MilanoMilanItaly
  2. 2.Scientific Direction, IRCCS Cà Granda Maggiore Hospital FoundationMilanItaly
  3. 3.IRCCS Cà Granda Maggiore Hospital FoundationMilanItaly

Personalised recommendations