JAK2V617F variant allele frequency prognostic of venous events in polycythaemia vera

JAK2V617F variant allele frequency (VAF) >50% was associated with an increased risk of venous thrombosis in patients with polycythaemia vera (PV). This independent predictor distinguished between patients who were classified as low-risk patients by classical risk modelling, demonstrating that conventional risk assessment may not be sufficient to tailor treatment regarding the prevention of venous thrombosis in patients with PV [1].

“Most patients with PV show a JAK2 mutation in exon 14 (JAK2V617F), and at diagnosis, the JAK2V617F VAF is highly heterogeneous in these patients,” said Dr Giuseppe Loscocco (University of Florence, Italy). “In addition, patients with PV have an increased risk of thrombosis.” Therefore, the current study aimed to evaluate the association between JAK2V617F VAF at diagnosis and the rate of arterial and venous thrombosis. In total, 865 cases were analysed.

JAK2V617F VAF was significantly associated with the risk of venous thrombosis (P=0.003) but not with arterial thrombosis (P=0.8). A ROC curve analysis determined that 50% VAF was the most accurate cut-off value to predict venous thrombosis in these patients. In addition, patients with a VAF >50% demonstrated higher white blood cells count (P=0.02), higher haematocrit and haemoglobin levels (P<0.0001), and a lower platelet count (P=0.0009). Multivariable analysis confirmed that VAF >50% (HR 3.8) and previous thrombosis (HR 2.2) were independent risk factors for subsequent venous thrombosis. In contrast, diabetes (HR 2.4), hyperlipidaemia (HR 2.3), and previous arterial events (HR 2.1) were significant predictors of future arterial thrombosis.

These results indicate that the risk factors for arterial and venous events are different and that these entities require separate management strategies. Notably, patients classified as low-risk patients for future venous thrombosis events by age and history of thrombotic events could be distinguished via JAK2V617F VAF values for their risk of future venous events. Therefore, conventional risk stratification by age and previous venous events may not be accurate enough to separate high-risk and low-risk patients. Dr Loscocco mentioned that future investigations should elucidate whether JAK2V617F VAF values >50% are useful to reclassify low-risk patients to high-risk patients.

1. Loscocco GG, et al. A JAK2V617F Variant Allele Frequency Greater Than 50% Identifies Patients with Polycythemia Vera at High Risk for Venous Thrombosis. Abstract 237, ASH 2021 Annual Meeting, 11–14 December.

 

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Posted on 4 February 2022