Blood Transfusion - 1 2010

Is JAK2V617F mutation absence a risk factor for bleeding in Essential Thrombocythemia? An analysis on 106 patients
Authors:  Andrea Patriarca, Franca Pompetti, Raniero Malizia, Ornella Iuliani, Ilaria Di Marzio, Antonio Spadano, Alfredo Dragani
Pages:  21-7
To cite this article:  Blood Transfus 2010; 8: 21-7
Doi:  10.2450/2009.0004-09
Published online:  14/04/2009

Background. JAK2V617Fmutation has been recognized as a possible thrombotic risk factor in essential thrombocythaemia (ET). It’s role is probably due to an increased myeloid proliferation and white blood cells (WBC) activation. Only few data are available about the effect of JAK2V617F on hemorrhagic risk. The aim of our study was to evaluate the influence of the mutational status on hemorrhagic complication. 
Methods. We retrospectively analysed laboratory and clinical findings of 106 consecutive patients with ET to evaluate possible relationships between thrombosis, abnormal bleeding, peripheral blood count, overexpression of PRV1 and JAK2V617F mutational status.
Results. On univariate analysis we found: an association between JAK2V617F mutation and thrombotic events before or at diagnosis (p<0.003, OR=4.44, 95% CI=1.74-12.4); no statistical correlation between the median value of JAK2V617F burden and an increased risk of thrombosis (p=0.4, 95% CI= –22.8-10.4); significant relationships between mutated status and higher haematocrit, high WBC count and low platelet count; and a strong correlation between JAK2V617F and PRV1 overexpression (p<0.0001). Moreover, the presence of the JAK2V617F mutation and a WBC count greater than 8.4x109/L were found to be independent factors related to thrombotic complications in multivariable analysis (p<0.006, OR=3.85, 95% CI=1.3-11.9; and p<0.002, OR=2.8, 95% CI=1.08-7.03, respectively). The prognostic impact of JAK2 mutation status and WBC count on thrombosis was evaluated in the whole cohort. Only new cases occurring in patients without previous thrombotic events were recorded for the analysis. The multivariable analysis showed a statistical correlation between the presence of the mutation and a WBC count greater than 8.12 x 106/L and an increased risk of thrombosis if no cytoreductive treatment was started at diagnosis (JAK2V617F p=0.02; WBC p=0.02; OR=4.97; 95% CI=1.04-23.8). Finally, wild-type JAK2 was associated with a higher haemorrhagic risk (p=0.02) in univariate analysis but only a platelet count greater than   1,022 x 109/L was associated with an increased risk of bleeding in the multivariable analysis.
Conclusion.Our data confirm the role of both JAK2V617F as factor associated with an increased risk of thrombosis at the diagnosis and during follow-up in no treated patients. Moreover a WBC count over 8.4x109/L1 was also strictly associated to an increased risk of thrombosis. Regarding bleedings, our statistical analysis allows to exclude the mutation protective role on haemorrhage.
Key words: essential thrombocythaemia, JAK2V617F, myeloproliferative disorders, thrombosis, bleeding.
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