Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia

Stefano, Valerio De; Zà, Tommaso; Rossi, Elena; Vannucchi, Alessandro M.; Ruggeri, Marco; Elli, Elena Maria; Micò, Caterina; Tieghi, Alessia; Cacciola, Rossella; Santoro, Cristina; Gerli, Giancarla; Guglielmelli, Paola; Pieri, Lisa; Scognamiglio, Francesca; Rodeghiero, Francesco; Pogliani, Enrico Maria; Finazzi, Guido; Gugliotta, Luigi; Leone, Giuseppe; Barbui, Tiziano

doi:10.1002/ajh.21593

Cited by 57 publications

(43 citation statements)

References 27 publications

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“…Recently, also the presence of JAK2V617F mutation [6][7][8] and baseline leukocyte (WBC) count have been considered as disease-related cardiovascular risk factors of ET patients. This latter has been found to play a biological role in determining thrombosis, mainly acute coronary syndromes, in CMPN and particularly in ET, although it is presently not completely defined whether elevated WBC levels actually contribute directly to causing thrombosis [9].…”

Section: Introductionmentioning

confidence: 99%

Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study

et al. 2011

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Established risk factors for thrombosis in Essential Thrombocythemia (ET) include age (≥60 years) and previous vascular events. Recently, also leukocytosis has been proposed in risk stratification of ET patients. We report a retrospective study on 532 ET patients followed for a median of 7.6 years. Sixty-four patients (12%) developed 95 thrombotic events during follow-up. Together with the high risk condition, a WBC value above 11x10 9 /L, corresponding to the fourth percentile value, significantly correlated with a higher thrombotic risk (p=0.033) by Cox proportional hazards. Moreover, the cumulative risk of thrombosis was significantly higher in high-risk patients with WBC>11x10 9

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Section: Introductionmentioning

confidence: 99%

Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study

et al. 2011

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“…In principle, leukocytosis-associated low platelet P2Y 12 function could result in a hemorrhagic tendency. In apparent contradiction, patients with high WBC counts have been reported to be more susceptible to thrombosis than bleeding [30,31,32]. P2Y 12 -independent mechanisms may account for the hypercoagulable state which has been reported to be associated with high WBC counts.…”

Section: Discussionmentioning

confidence: 68%

“…The WBC count was found to be an independent risk factor for thrombosis in MPN patients [29,30,31,32]. …”

Section: Discussionmentioning

confidence: 99%

Clinical and Laboratory Significance of Defective P2Y<sub>12</sub> Pathway Function in Patients with Myeloproliferative Neoplasms: A Pilot Study

Chang

Shih²,

Michelson³

et al. 2013

Acta Haematol

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Background: Patients with myeloproliferative neoplasms (MPN) have an increased risk for thrombosis and bleeding and show a defect in adenosine diphosphate (ADP)-induced platelet aggregation. This risk of thrombosis is further increased in MPN patients bearing the JAK2V617F mutation. Two ADP receptors, P2Y₁ and P2Y₁₂, are present on platelets. Although the pattern of defective ADP-induced platelet aggregation in MPN suggests an abnormality in the P2Y₁₂ pathway, no previous studies have specifically evaluated P2Y₁₂ function in MPN or the relationship between P2Y₁₂ function and the JAK2V617F mutation. Methods: Forty-one MPN patients were enrolled, including 24 with essential thrombocythemia (ET), 16 with polycythemia vera (PV) and 1 with primary myelofibrosis. Platelet P2Y₁₂ function in MPN was evaluated by flow-cytometric measurement of the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Clinical data were collected by review of medical records. JAK2V617F mutation was detected by allele-specific polymerase chain reaction. JAK2V617F allele burden was measured by the pyrosequencing method. Results: In patients with MPN, platelet P2Y₁₂ function determined by VASP platelet reactivity index (PRI) was inversely correlated with platelet and white blood cell (WBC) counts. In subgroup analysis, PRI was inversely correlated with platelet and WBC counts in PV. PRI was also inversely correlated with platelet counts in ET, but the correlation of PRI and WBC counts did not reach statistical significance. Eight of the 41 patients had a history of thrombosis and only 2 had a bleeding history. Neither thrombosis nor bleeding patients were found to have significantly different PRIs. JAK2V617F mutation data were available in 35 cases. PRI was not different between JAK2V617F mutation and wild-type patients but PRI had a trend towards an inverse correlation with JAK2V617F allele burden for patients with mutations. Conclusions: The present study provides the first explicit demonstration of a defect in the P2Y₁₂ pathway in platelets of patients with MPN. Furthermore, platelet P2Y₁₂ function, assayed by VASP, is inversely correlated with platelet and WBC counts in patients with MPN. Platelet P2Y₁₂ function also appears to be inversely correlated with JAK2V617F allele burden. This compromised P2Y₁₂ function may be a novel mechanism for the bleeding tendency associated with extreme thrombocytosis in MPN.

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“…The previous two cases were characterized by increased leukocyte and hematocrit counts, whereas the case described here was characterized by elevated leukocyte counts and platelet levels. It is reported that a JAK2 V617 mutation affects the number and activation of WBCs (17). Landolfi reported that the risk of thrombosis was significantly increased when the WBC count was >10x10 9 /l in patients with PV (13), although the underlying mechanism of thrombosis remains to be fully elucidated (18).…”

Section: Discussionmentioning

confidence: 99%

Ischemic colitis caused by polycythemia vera: A case report and literature review

et al. 2018

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Abstract. Polycythemia vera (PV) is a chronic myeloproliferative disorder originating from hematopoietic stem cells and complicated by thrombosis and bleeding. This report describes a case of ischemic colitis (IC) caused by PV and includes a review of the relevant literature. The patient was a 59-year-old male with a history of PV who presented with abdominal pain and hematochezia. Colonoscopy and histopathological examination results indicated suspected ischemic bowel disease. Following experimental anticoagulant therapy for 7 days, the patient no longer experienced abdominal pain and hematochezia had resolved. Colonoscopy review showed no obvious anomalies 1 month later. These data demonstrated that PV is an uncommon cause of IC.

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Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia

Cited by 57 publications

References 27 publications

Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study

Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study

Clinical and Laboratory Significance of Defective P2Y<sub>12</sub> Pathway Function in Patients with Myeloproliferative Neoplasms: A Pilot Study

Ischemic colitis caused by polycythemia vera: A case report and literature review

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