Thrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia

Abstract

To elucidate the role of thrombocytosis, alone or in combination with standard (age, previous cardiovascular events) and novel (leukocytosis, JAK2(V617F) mutational status) risk factors, in the cardiovascular events of essential thrombocythemia (ET), we analyzed a cohort of 1063 patients. We found that a platelet count at diagnosis greater than 1000 x 10(9)/L was associated with significantly lower rate of thrombosis in multivariable analysis and, if combined with leukocytes less than 11 x 10(9)/L, pointed to a "low-risk" category with a rate of thrombosis of 1.59% of patients/year. On the contrary, the highest risk category (thrombosis rate, 2.95% of patients/year) was constituted of patients with leukocytosis, lower platelet count, and a JAK2(V617F) mutated genotype in most cases (77% vs 26% in the low-risk group), independently from standard risk factors. These data challenge the theory that elevated platelet count increases thrombosis risk in ET and suggest prospective clinical trials to support this hypothesis.

The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy

“…14 Hemorrhagic complications are less frequent, approximately 0.33% per year, 9 possibly due to an acquired von Willebrand-like defect, associated with the highest platelet counts. 15,16 In addition to the clinical evidence of a predominantly arterial thrombotic diathesis, several groups have reported evidence of platelet activation in vivo or ex vivo in ET. 17,18 We have previously reported enhanced urinary excretion of thromboxane (TX) metabolites (TXMs) in untreated ET patients.…”

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia

“…In our study, the analysis of possible risk factors for vascular events examined at diagnosis reveals that neither blood count, nor cardiovascular risk factors nor JAK2 mutations are predictive for thrombosis or hemorrhage during follow-up. Carobbio et al suggest an association between leukocytosis at diagnosis and thrombosis [10]. However, other studies do not show that platelet or leukocyte counts at presentation are predictive of subsequent vascular events [12,14].…”

“…However, agreement is lacking about the role of blood counts in this risk. A relationship between high WBC ([11 9 10 9 /L) and the risk of thrombosis has been shown, [9,10] but these findings have been contradicted by other authors [11][12][13]. Recently, Passamonti et al re-examined this issue using a dynamic model based on two sequential evaluations of WBC count within 2 years from diagnosis, and find that patients with an increase greater than one-third of the baseline WBC count, have a significantly higher risk of developing thrombosis [14].…”

NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018

“…[6][7][8][9][10] Data from some studies suggest that the prognostic significance of leukocytosis for the risk of recurrent thrombosis may be significant only in patients aged <60 years, 11,12 and other studies have reported that leukocytosis at diagnosis is not associated with the risk of subsequent thrombosis. 13 Thrombocytosis (platelet count >1,000 x 10 9 /L) has been associated with an immediate risk of major hemorrhage but not with the risk of thrombosis in patients with ET.…”

“…10 In fact, some studies have reported that elevated platelet counts at diagnosis (>1,000 x 10 9 /L) is associated with a significantly lower rate of thrombosis, and this association was significant even in patients with JAK2-mutated ET. 8,9 The potential benefit of initiation of cytoreductive therapy based on elevated blood counts (leukocytosis or thrombocytosis) at diagnosis has not been evaluated in prospective studies.…”