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JAK2V617F allele burden is associated with thrombotic mechanisms activation in polycythemia vera and essential thrombocythemia patients

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Abstract

The clinical courses of polycythemia vera (PV) and essential thrombocythemia (ET) are characterized by thrombohemorrhagic diathesis. Several groups have suggested an association between JAK2V617F mutation and thrombosis. We hypothesized a relationship between JAK2V617F allele burden, cellular activation parameters, and thrombosis. We evaluated a group of PV and ET patients using flow cytometry: platelet CD62P, CD63, and dense granules, platelet–leukocyte aggregates (PLA), leukocyte CD11b and monocyte tissue factor (TF) expression. All patients had increased baseline platelet CD62P and CD63 expression (p < 0.05); 71 % of PV and 47 % of ET presented with a storage pool disease. Leukocyte CD11b, TF, and PLA were elevated in all patients. TF was higher in PV compared to ET (p < 0.05) and platelet–neutrophil [polymorphonuclear (PMN)] aggregates were increased in ET versus PV (p < 0.05). In ET, PLA were correlated with platelet numbers (p < 0.05). In all patients, JAK2V617F allele burden was directly correlated with monocyte CD11b. Patients with JAK2V617F allele burden >50 % presented higher levels of leukocyte activation. In ET, thrombosis was associated with JAK2V617F mutation (p < 0.05, χ 2 = 5.2), increased monocyte CD11b (p < 0.05) and with platelet-PMN aggregates (p < 0.05). In ET patients, hydroxyurea does not significantly reduce the activation parameters. Our data demonstrate that JAK2V617F allele burden is directly correlated with activation parameters that drive mechanisms that favor thrombosis.

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Acknowledgments

This study was supported by the Grant PTDC/SAU-GMG/74375/2006 from the Portuguese Foundation for Science and Technology, FCT, Portugal.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Serviço Hematologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, Av. Afonso Romão, Santo António dos Olivais, 3000-075, Coimbra, Portugal

    Margarida Coucelo, Gonçalo Caetano, Teresa Sevivas, Susana Almeida Santos, Teresa Fidalgo, Celeste Bento, Manuela Fortuna, Marta Duarte, Cristina Menezes & M. Letícia Ribeiro

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  1. Margarida Coucelo
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  2. Gonçalo Caetano
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  3. Teresa Sevivas
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  4. Susana Almeida Santos
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  5. Teresa Fidalgo
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  6. Celeste Bento
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  7. Manuela Fortuna
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  8. Marta Duarte
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  9. Cristina Menezes
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  10. M. Letícia Ribeiro
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Correspondence to Margarida Coucelo.

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Coucelo, M., Caetano, G., Sevivas, T. et al. JAK2V617F allele burden is associated with thrombotic mechanisms activation in polycythemia vera and essential thrombocythemia patients. Int J Hematol 99, 32–40 (2014). https://doi.org/10.1007/s12185-013-1475-9

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  • DOI: https://doi.org/10.1007/s12185-013-1475-9

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