title: JAK2V617F allele burden is associated with thrombotic mechanisms activation in polycythemia vera and essential thrombocythemia patients.
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.
authors.affiliation: Serviço Hematologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, Av. Afonso Romão, Santo António dos Olivais, 3000-075, Coimbra, Portugal, margarida.coucelo@chc.min-saude.pt.
authors.forename: Margarida
authors.initials: M
authors.lastname: Coucelo
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Caetano
authors.forename: Teresa
authors.initials: T
authors.lastname: Sevivas
authors.forename: Susana
authors.initials: S
authors.lastname: Almeida Santos
authors.forename: Teresa
authors.initials: T
authors.lastname: Fidalgo
authors.forename: Celeste
authors.initials: C
authors.lastname: Bento
authors.forename: Manuela
authors.initials: M
authors.lastname: Fortuna
authors.forename: Marta
authors.initials: M
authors.lastname: Duarte
authors.forename: Cristina
authors.initials: C
authors.lastname: Menezes
authors.forename: M Letícia
authors.initials: ML
authors.lastname: Ribeiro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001792:Blood Platelets / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D016022:Case-Control Studies; D003062:Codon; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D011087:Polycythemia Vera / Q000150:complications* / Q000235:genetics*; D011796:Quinacrine / Q000378:metabolism; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000235:genetics*; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology*; D055815:Young Adult
chemical_list: D039481:CD11b Antigen; D003062:Codon; D013925:Thromboplastin; D053614:Janus Kinase 2; D011796:Quinacrine