Esansiyel Trombositozlu Hastalarda Tromboembolizmin Mutasyon Durumuna Göre Değerlendirilmesi; Tek Merkez Deneyimi

Year 2021, Volume: 54 Issue: 3, 429 - 433, 01.01.2022

Hikmettullah Batgi

https://doi.org/10.20492/aeahtd.1015643

Abstract

ABSTRACT
Aim: The presence of Janus kinase 2 (Jak2) mutation in essential thrombocytosis (ET) patients is associated with an increased risk of thrombosis, while the presence of calreticulin (Calr) mutation is associated with a decrease in thrombosis risk. The aim of this study is to compare patients with mutation (Jak2, Calr, myeloproliferative leukemia virus oncogene [Mpl]) and non-mutation (triple-negative) patients in terms of the development of thromboembolism.
Methods: 95 patients who were followed up with the diagnosis of ET between 2009 and 2020 were included in this study. The clinical characteristics, laboratory results, and mutation status of the patients were analyzed retrospectively, based on the patients’ files. The patients in mutation positive (Jak2, Calr, Mpl) group a, only jak2 mutation-positive group b, and triple-negative (Jak2, Calr, Mpl negative) group c were compared.
Results: The median age of ET patients was 53 years (18-91). The Jak2 mutation was found positive in 42% (n:40) of the patients with ET. 4 patients (4%) were calr mutation-positive, but mpl mutation was not detected. 51 patients (54%) were triple-negative. A total of 22 (23%) patients had a thrombotic event at diagnosis and follow-up. Thrombotic events were detected in 27.5% (11/44) of the patients with positive Jak2 mutation and in 21.5% (11/51) of the patients with triple-negative. No thrombotic event was detected in 4 patients with a positive calr mutation. No statistically significant difference was found for thrombotic events in mutation-positive patients compared with triple-negative patients (p = 0.7). No statistically significant difference was found in terms of white blood cell count, thrombocyte count and spleen size examined at the time of diagnosis. When compared in terms of hemoglobin, age and gender distribution (male / female), the difference was found statistically significant in those with positive mutation (p = 0.001 *, p = 0.001 *, p = 0.03*).
Discussion and Conclusion: The results of this study showed that Jak2V617F gene mutation is an important finding for diagnosis and complications in patients with ET, and its presence increases the risk of thrombosis development. The presence of calr mutation reduces the risk of thrombosis and appears at an earlier age than Jak2V617F mutation. Thrombosis risk in triple-negative ET patients is similar to the one in patients with Jak2V617F mutation.

Keywords

Essential thrombocythemia, mutation status, thromboembolism

Evaluation of Thromboembolism According to Mutation Status in Patients with Essential Thrombocytosis; Single-Center Experience

Abstract

ABSTRACT
Aim: The presence of Janus kinase 2 (Jak2) mutation in essential thrombocytosis (ET) patients is associated with an increased risk of thrombosis, while the presence of calreticulin (Calr) mutation is associated with a decrease in thrombosis risk. The aim of this study is to compare patients with mutation (Jak2, Calr, myeloproliferative leukemia virus oncogene [Mpl]) and non-mutation (triple-negative) patients in terms of the development of thromboembolism.
Methods: 95 patients who were followed up with the diagnosis of ET between 2009 and 2020 were included in this study. The clinical characteristics, laboratory results, and mutation status of the patients were analyzed retrospectively, based on the patients’ files. The patients in mutation positive (Jak2, Calr, Mpl) group a, only jak2 mutation-positive group b, and triple-negative (Jak2, Calr, Mpl negative) group c were compared.
Results: The median age of ET patients was 53 years (18-91). The Jak2 mutation was found positive in 42% (n:40) of the patients with ET. 4 patients (4%) were calr mutation-positive, but mpl mutation was not detected. 51 patients (54%) were triple-negative. A total of 22 (23%) patients had a thrombotic event at diagnosis and follow-up. Thrombotic events were detected in 27.5% (11/44) of the patients with positive Jak2 mutation and in 21.5% (11/51) of the patients with triple-negative. No thrombotic event was detected in 4 patients with a positive calr mutation. No statistically significant difference was found for thrombotic events in mutation-positive patients compared with triple-negative patients (p = 0.7). No statistically significant difference was found in terms of white blood cell count, thrombocyte count and spleen size examined at the time of diagnosis. When compared in terms of hemoglobin, age and gender distribution (male / female), the difference was found statistically significant in those with positive mutation (p = 0.001 *, p = 0.001 *, p = 0.03*).
Discussion and Conclusion: The results of this study showed that Jak2V617F gene mutation is an important finding for diagnosis and complications in patients with ET, and its presence increases the risk of thrombosis development. The presence of calr mutation reduces the risk of thrombosis and appears at an earlier age than Jak2V617F mutation. Thrombosis risk in triple-negative ET patients is similar to the one in patients with Jak2V617F mutation.

Keywords

Essential thrombocythemia, mutation status, thromboembolism

References

• Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-405.
• Cazzola M, Kralovics R. From Janus kinase 2 to calreticulin: the clinically relevant genomic landscape of myeloproliferative neoplasms. Blood. 2014;123:3714–19.
• Rumi E, Pietra D, Pascutto C, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators. Blood. 2014 ;124:1062-9.
• Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management. American journal of hematology. 2015;90:162-73.
• Barbui T, Thiele J, Passamonti F, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29:3179-84.
• Tefferi A, Wassie EA, Guglielmelli P, et al. Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: a collaborative study of 1027 patients. American Journal of Hematology. 2014;89:121-4.
• 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.
• Elliott MA, Tefferi A. Thrombosis and hemorrhage in polycythemia vera and essential thrombocythemia. Br J Haematol. 2005;128:275-90.
• Palandri F, Polverelli N, Catani L, et al. Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study. Ann Hematol. 2011;90:933-38.
• Soyer N, Haznedaroğlu İC, Cömert M, et al. Multicenter Retrospective Analysis of Turkish Patients with Chronic Myeloproliferative Neoplasms.Turk J Haematol. 2017;34:27-33.
• Chim CS, Kwong YL, Lie AK, et al. Long-term outcome of 231 patients with essential thrombocythemia: prognostic factors for thrombosis, bleeding, myelofibrosis, and leukemia. Arch Intern Med. 2005;165:2651-58.
• Tefferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood, The Journal of the American Society of Hematology. 2014; 124: 2507-13.
• Passamonti F, Thiele J, Girodon F, et al. A prognostic model to predict survival in 867 World Health Organization–defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment. Blood. 2012; 120: 1197-201.