head JofIMAB
Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing
ISSN: 1312-773X (Online)
Issue: 2018, vol. 24, issue3
Subject Area: Medicine
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DOI: 10.5272/jimab.2018243.2085
Published online: 09 July 2018

Original article

J of IMAB. 2018 Jul-Sep;24(3):2085-2090
EVALUATION OF THE CORRELATION BETWEEN JAK2V617F, LEUCOCYTOSIS AND THROMBOGENIC RISK IN PATIENTS WITH POLYCYTHEMIA VERA AND ESSENTIAL THROMBOCYTHEMIA
Antonio Antonov1ORCID logo Corresponding Autoremail, Liana Gercheva1ORCID logo, Nadezhda Stefanova2ORCID logo, Maria Tzaneva3ORCID logo, Trifon Chervenkov4ORCID logo,
1) Clinic of Haematology, University Hospital St. Marina, Medical University, Varna, Bulgaria.
2) Department of General and Clinical Pathology, Faculty of Medicine, Medical University, Varna, Bulgaria.
3) Department of Preclinical and Clinical Sciences, Faculty of Pharmacy, Medical University, Varna, Bulgaria.
4) Clinical sciences, Department of Medical Genetics, Faculty of Pharmacy, Medical University, Varna, Bulgaria.

ABSTRACT:
Thrombotic events (TE) are the most common, debilitating and fatal complications in Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Approximately 20% of patients have experienced TE at the time of diagnosis. The subsequent cumulative incidence of non-fatal thrombosis is 3.8 incidents/100 patients / year [1, 2]. The risk stratification divides patients by age and a history of thrombosis. There is controversy in the literature about the impact of JAK2 V617F allel burden and changes in peripheral blood counts on the TE frequency.
Aim: The aim of this study is to evaluate the influence of JAK2 V617F allel burden and changes in leukocyte count on the development of thrombotic events in patients with PV and ET.
Methods: We performed a retrospective analysis of the data of 96 patients with PV and 43 patients with ET diagnosed according to the WHO criteria. JAK2 mutational burden was determined by RealTime-PCR. The statistical analysis was performed with SPSS 19.0 software.
Results: In the group of PV patients, thrombotic events were recorded in 46 patients. We did not find a correlation between higher levels of JAK2 V617F allel burden and frequency of TE. Clinically, patients with a higher mutational burden had more pronounced splenomegaly. There was no correlation between leukocytosis at the diagnosis and the number of TE, but there was a significant correlation between leukocytosis and the presence of splenomegaly.
In the group of ET patients (43) we established TE in 13 of them, and 54% were carriers of JAK2 V617F. There was no relationship between the frequency of TE and the increased leukocyte count. Unlike PV patients, the presence of JAK2 V617F≥50% was associated with pronounced leukocytosis in the group with ET patients.
Conclusions: The JAK2 V617F allel burden and leukocytosis level are prothrombogenic, but are not a predetermining factor for thrombosis. The current risk stratification criteria for PV and ET, although common, reflect the complexity of thrombotic complications. Clotting mechanisms are different not only in both diseases but also in different parts of the vascular system. More studies are needed involving the functional state of the vascular system to help differentiate individual arterial and venous thrombotic index for each disease.

Keywords: JAK2 V617F mutation, thrombosis, myeloproliferative neoplasm, polycythaemia vera (PV), essential thrombocythaemia (ET), leukocytosis, splenomegaly, risk stratification,

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Please cite this article as: Antonov A, Gercheva L, Stefanova N, Tzaneva M, Chervenkov T. Evaluation of the correlation between JAK2V617F, leucocytosis and thrombogenic risk in patients with Polycythemia Vera and Essential thrombocythemia. J of IMAB. 2018 Jul-Sep;24(3):2085-2090.
DOI: 10.5272/jimab.2018243.2085

Corresponding AutorCorrespondence to: Antonio Ivanov Antonov, MD. Clinic of Hematology, University Hospital St. Marina – Varna; 1, Hristo Smirnenski blvd., 9000 Varna, Bulgaria; E-mail: aantov@abv.bg,

REFERENCES:
1. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan;350(2):114-24. [PubMed] [CrossRef]
2. Kroll MH, Michaelis LC, Verstovsek S. Mechanisms of thrombogenesis in polycythemia vera. Blood Rev. 2015 Jul;29(4):215-21. [PubMed] [CrossRef]
3. Caramazza D, Caracciolo C, Barone R, Malato A, Saccullo G, Cigna V, et al. Correlation between leukocytosis and thrombosis in Philadelphia-negative chronic myeloproliferative neoplasms. Ann Hematol. 2009 Oct;88(10):967-71. [PubMed] [CrossRef]
4. De Stefano V, Za T, Rossi E, Vannucchi AM, Ruggeri M, Elli E, et al. Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments. Haematologica. 2008 Mar;93(3):372-80. [PubMed] [CrossRef]
5. Di Nisio M, Barbui T, Di Gennaro L, Borrelli G, Finazzi G, Landolfi R, et al. The haematocrit and platelet target in polycythemia vera. Br J Haematol. 2007 Jan;136(2):249-59. [PubMed] [CrossRef]
6. Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A. Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. Br J Haematol. 2007 Aug;138(3):354-8. [PubMed] [CrossRef]
7. Grinfeld J, Nangalia J, Green AR. Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms. Haematologica. 2017 Jan;102(1):7-17. [PubMed] [CrossRef]
8. Vannucchi AM, Antonioli E, Guglielmelli P, Longo G, Pancrazzi A, Ponziani V, et al. Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia. 2007 Sep;21(9):1952-9. [PubMed] [CrossRef]
9. Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood. 2007 Aug 1;110(3):840-6. [PubMed] [CrossRef]
10.Swystun LL, Liaw PC. The role of leukocytes in thrombosis. Blood. 2016 Aug 11;128(6):753-62. [PubMed] [CrossRef]
 11. Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. 2007 Mar 15;109(6):2446-52. [PubMed] [CrossRef]
12. Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012 Dec 20;120(26):5128-33; quiz 5252. [PubMed] [CrossRef]
13. Barbui T, Vannucchi AM, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J. 2015 Nov 27;5:e369. [PubMed] [CrossRef]
14. Rumi E, Cazzola M. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood. 2017 Feb 9;129(6):680-692. [PubMed] [CrossRef]
15. Spivak JL. Myeloproliferative Neoplasms. N Engl J Med. 2017 Aug 31;377(9):895-6. [PubMed] [CrossRef]
16. Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005 Apr 1;23(10):2224-32. [PubMed] [CrossRef]
17. Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013 Jan 3;368(1):22-33. [PubMed] [CrossRef]
18. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. [PubMed] [CrossRef]
19. Passamonti F, Rumi E, Pietra D, Elena C, Boveri E, Arcaini L, et al. A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia. 2010 Sep;24(9):1574-9. [PubMed] [CrossRef].

Received: 26 February 2018
Published online: 09 July 2018

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