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

2017, vol. 26, nr 1, January-February, p. 115–121

doi: 10.17219/acem/68578

Publication type: original article

Language: English

Download citation:

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

Predictive factors of thrombosis for patients with essential thrombocythaemia: A single center study

Iwona Prajs1,A,B,C,D,E,F, Kazimierz Kuliczkowski1,F

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

Abstract

Background. Thrombotembolic complications are the leading cause of mortality in essential thrombocythemia (ET), but the definition of thrombotic risk remains far from clear.
Objectives. The aim of this study was to evaluate the prognostic markers for thrombosis to identify ET patients at risk.
Material and Methods. Forty-five consecutive patients with ET were studied. This group was divided into two subgroups ET patients with (A) and without (B) history of thrombosis. Each patient has been tested for complete blood count, fibrinogen, factor VIII, D-dimer, protein C, APCR, TAT and F1+2. JAK2 mutation was assessed by RT-PCR. Factor V Leiden and prothrombin genes mutations were screened by DNA sequencing.
Results. The median age of ET patients was 62.0 years. JAK2 mutation was found in 24 patients, 21 of them had a history of thrombotic events, and 17/21 were JAK2 positive. Compared to controls, ET patients had a significantly higher WBC and PLT counts, and higher mean platelet volume (MPV), but not Hgb level or RBC count. In ET subgroup A, apart from changes seen in the whole ET, the Hgb level, RBC count, and Hct were also significantly elevated. Interestingly, the MPV was significantly larger in subgroup A, but not in B. Fibrinogen and D-dimers levels were significantly higher in ET group than in controls, but not F1+F2 or TAT. The results of hemostatic tests did not markedly differ between subgroups A and B. APCR was found in 5/45 patients with ET, and 2 out of 5 had a factor V Leiden heterozygous mutation. No prothrombin gene mutation was observed.
Conclusion. Our results suggest that MPV can serve as a simple test for assessing the hypercoagulable state in ET patients. It has been confirmed that JAK2 mutation and leukocytosis are independent predictors for thrombotic events in ET patients.

Key words

essentials thrombocythaemia, thrombosis, JAK2 mutation, platelets, leukocytes

References (27)

  1. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005; 352:1779–1790.
  2. Vainchenker W, Delhommeau F, Constantinescu SN, Bernard OA. New mutations and pathogenesis of myeloproliferative neoplasms. Blood. 2011;118:1723–1735.
  3. Rotunno G, Mannarelli C, Guglielmelli P, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythaemia. Blood. 2014;123:1552–1555.
  4. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organisation diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007;110:1092–1097.
  5. Tefferi A, Barbui T. Personalized management of essential thrombocythemia: application of recent evidence to clinical practice. Leukemia. 2013;27:1617–1620.
  6. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008;22:14–22.
  7. Carobbio A, Finazzi G, Guerini V, et al. Leukocytosis is a risk stratification assessment in essential thrombocythemia. J Clin Oncol. 2008;26:2732–2736.
  8. De Stefano V, Za T, Rossi E, et al. Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essentials thrombocythemia. Haematologica. 2009; 94:733–737.
  9. Dahabreh IJ, Zoi K, Giannouli S, Zoi C, Loukopoulos D, Voulgarelis M. Is JAK2 V617F mutation more than a diagnostic index? A meta-analysis of clinical outcomes in essential thrombocythemia. Lek Res. 2009;33: 67–73.
  10. Amitrano L, Guardascione MA, Ames PRJ, et al. Thrombophilic genotypes, natural anticoagulants, and plasma homocysteine in myeloprolif-erative disorders: Relationship with splanchnic vein thrombosis and arterial disease. Ann J Hematol. 2003;72:75–81.
  11. Afshar-Kharghan V, López JA, Gray LA, Padilla A, Borthakur G, Roberts SC, Pruthi RK, Tefferi A. Hemostatic gene polymorphisms and the prev-alence of thrombotic complications in polycythemia vera and essential thrombocythemia. Blood Coagul Fibrinolysis. 2004;15:21–24.
  12. Gisslinger H, Rodeghiero F, Ruggeri M, et al. Homocysteine levels in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 1999;105:551–555.
  13. Schwartz J, Ovesna P, Cerna O, et al. Thrombosis in thrombocythemic Ph-myeloproliferations is associated with higher platelet count prior to the event: results of analysis of prothrombotic risk factors from a registry of patients treated with anagrelide. Eur J Haematol. 2016;96:98–106.
  14. Vannucchi AM, Barbui T, Cervantes F, et al. On behalf of the ESMO Guidelines Committee: Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26 Suppl 5:85–95.
  15. Arber DA, Orazi A, Hasserjian R, et al. The updated WHO classification of hematological malignancies. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–2405.
  16. Barbui T, Finazzi G, Corobbio A, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Or-ganization – Essential Thrombocythemia (IPSET-thrombosis). Blood. 2012;120:5128–5133.
  17. Belluci S, Michiels JJ. The role of JAK2 V617F mutation, spontaneous erythropoiesis and megakaryocytopoiesis, hypersensitive platelets, activated leukocytes, and endothelial cells in etiology of thrombotic manifestations in polycythemia vera and essential thrombocythaemia. Semin Thromb Hemost. 2006;32:381–398.
  18. Arellano-Rodrigo E, Alvarez-Larran A, Reverter JC, et al. Automated assessment of the neutrophil and platelet activation status in patients with essential thrombocythaemia. Platelets. 2012;23:336–343.
  19. Arellano-Rodrigo E, Alvarez-Larran A, Reverter JC, et al. Platelet turnover, coagulation factors, and soluble markers of platelet and endothe-lial activation in essential thrombocythaemia: relationship with thrombosis occurence and JAK2 V617F allele burden. Am J Hematol. 2009;84:102–108.
  20. Arellano-Rodrigo E, Alvarez-Larrán A, Reverter JC, et al. Increased platelet and leukocyte activation as contributing mechanisms for throm-bosis in essential thrombocythemia and correlation with the JAK2 mutational status. Haematologica. 2006;91:169–175.
  21. Marchetti M, Castoldi E, Spronk HM, et al. Thrombin generation and activated protein C resistance in patients with essential thrombocythe-mia and polycythemia vera. Blood. 2008;112:4061–4068.
  22. Cervantes F, Arellano-Rodrigo E, Alvarez-Larrán. Blood cell activation in myeloproliferative neoplasms. Haematologica. 2009;94: 1484–1488.
  23. Blann A, Caine G, Bareford D. Abnormal vascular, platelet and coagulation markers in primary thrombocythaemia are not reversed by treat-ments that reduce the platelet count. Platelets. 2004;15:447–449.
  24. Falanga A, Marchetti M, Vignoli A, Balducci D, Barbui T. Leukocyte-platelet interaction in patients with essential thrombocythaemia and polycythemia vera. Exp Hematol. 2005;33:523–530.
  25. Robertson B, Urquhart C, Ford I, Townend J, Watson HG, Vickers MA, et al. Platelet and coagulation activation markers in myeloproliferative diseases: relationships with JAK2 V617 F status, clonality, and antiphospholipid antibodies. J Thromb Haemost. 2007;5:1679–1685.
  26. Treliński J, Wierzbowska A, Krawczyńska A, Sakowicz A, Pietrucha T, Smolewski P, Robak T, Chojnowski K. Circulating endothelial cells in essential thrombocythemia and polycythemia vera: correlation with JAK2-V617F mutational status, angiogenic factors and coagulation ac-tivation markers. Int J Hematol. 2010;91792–91792–8. doi: 10.1007/s12185-010-0596-7. Epub 2010 May 15.
  27. Kaifie A, Kirschner M, Wolf D, et al. Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): Analysis from the German SAL-MPN-registry. J Hematol Oncol. 2016;9:18. doi: 10.1186/s13045-016-0242-9.
© Wroclaw Medical University