Effect Of Heterozygous JAK2 V617F On Thrombotic Risk In Patients With Polycythemia Vera: Measuring The Uncertain

The Janus Kinase (JAK)2 V617F mutation and its homozygous allele burden influences the thrombotic risk in Ph-negativemyeloid chronic disorders. Recent studies report that the vera polycythemia (PV) is a heterozygous JAK2V617F disease. The heterozygous PV is characterized by high hemoglobin (Hb), hematocrit (HCT) and red blood cell (RBC) and low thrombocytosis. Therefore, we evaluated allele burden, Hb, HCT, RBC and platelets and the occurrence of thrombotic events in patients with heterozygous PV disease. The study group included 50 patients (30 male, 20 female, mean age 68 years) affected by PV according WHO criteria. Their mean duration of disease was 11 years (range, 1-26 years). All patients were on aspirin. The percentage of granulocyte mutant alleles was evaluated using a quantitative real-time polymerase chain reaction-based allelic discrimination assay. Hb, HCT, RBC, platelets were measured by automated analyser. Of 50 patients, 28 had allele burden > 10% (34±5) and 22 had allele burden < 10% (6±1)). 10/28 had thrombosis (35%) including 6 transient ischemic attack (TIA), 2 myocardial infarction (MI) and 2 deep vein thrombosis (DVT), 18/22 (81%) had thrombosis including 8 transient ischemic attack (TIA), 4 myocardial infarct (MI) and 6 deep vein thrombosis (DVT). HB, HCT and RBC were elevated in all patients (19±1.8 g/dl, 56±4 %, 7±0.6 x106/L) and the platelets were higher in patients with allele burden > 10% than the patients with allele burden < 10% (500±127x109/L vs 381±128x109/L) (p = 0.030) whereas the thrombosis were more in patients with allele burden < 10% than the patients with allele burden > 10% (81% vs 35%). These data suggest that the heterozygous allele burden is a uncertain thrombotic risk factor.