Gene Variant Frequency May Predict VT Risk in Polycythemia Vera Patients

By Patrick Daly - Last Updated: December 20, 2021

In patients with polycythemia vera (PV), arterial thrombosis (AT) and venous thrombosis (VT) events are common complications and are the leading causes of PV-related morbidity and mortality. In a study published in Blood Cancer Journal, researchers examined the impact of the JAK2V617F variant allele frequency (VAF) on the rate of AT and VT events in patients with PV and found that JAK2V617 VAF over 50% was a strong, independent predictor of VT, though not AT. Co–lead authors, Paola Guglielmelli, MD, and Giuseppe G Loscocco, MD, suggested that their findings supported the notion that “AT and VT are different entities which might require distinct management.”

Further, “in parallel to conventional risk stratification, JAK2V617F VAF might receive consideration for an individualized risk assessment,” the report stated, but also acknowledged that, “whether this should result in modification of the current treatment approach is beyond the scope of this work and would require prospective evaluation.”


The study was conducted on a total of 865 patients with PV in separate training (n = 576) and validation (n = 289) cohorts.

In the training cohort, VT–free survival was significantly shorter in patients with over 50% JAK2V617F VAF (hazard ratio [HR] = 4; P?<0.0001). Notably, no difference was observed in AT (HR = 0.9, P?=?0.8). The investigator’s multivariable analysis identified JAK2V617F VAF?>50% (HR = 3.8, P?=?0.001) and VT (HR = 2.2, P?=?0.04) as independent risk factors for future VT. Meanwhile, diabetes (HR = 2.4, P?=?0.02), hyperlipidemia (HR = 2.3, P?=?0.01), and previous AT (HR = 2, P?=?0.04) were identified as independent risk factors for future AT.

In the validation cohort, JAK2V617F VAF?>50% (HR = 2.4, P?=?0.01) and previous VT (HR = 2.8, P?=?0.005) were also found to be independent predictors of VT events. Of note, JAK2V617F VAF?>50% had significant impact on VT for conventionally low–risk patients in both the training (HR 10.6, P?=?0.005) and validation (HR = 4, P?=?0.02) cohort.

The study was limited by its retrospective design and narrow focus on the VAF without collecting data on potential cofounders for the association with thrombosis. According to the authors, “the intrinsic potential drawbacks of the retrospective design could explain the differences in the incidence rate of thrombosis between the training and validation cohort.”

In conclusion, the authors did not aim to produce a new risk model for thrombotic events in patients as the VAF was only associated with VT. However, they advised that “these findings suggest the classical thrombotic risk model based on age and previous thrombosis may not be enough informative to tailor adequate treatment, especially in the setting of VT prevention.”