Association of Hyperuricemia with Thrombosis in Philadelphia-Negative Chronic Myeloproliferative Neoplasms
Authors: Pulido Mariem , Tuna Aguilar Elena , Sosa Romero Junice Teresita 
Published: December 2024

INTRODUCTION
Elevation of uric acid (UA) in chronic myeloproliferative neoplasms (cMPN) has been attributed to an increase in production by clonal neoplasm cells and a decrease in its excretion due to a decreased glomerular filtration rate (GFR) [1]. A few studies have associated hyperuricemia with a higher risk of thrombosis in cMPN, comparing essential thrombocythemia (ET) and polycythemia vera (PV).
Elevated levels of UA have been associated with a higher risk of cardiovascular morbidity and mortality. Thrombosis is a frequently encountered event in cMPN, mainly in polycythemia vera PV and ET; elevated UA could be considered as an independent risk factor regardless of mutational status in cMPN.
OBJECTIVES
To establish whether hyperuricemia constitutes a risk factor in chronic myeloproliferative neoplasms for thrombotic events compared to other known risk factors.
MATERIALS AND METHODS
We conducted a retrospective study in patients over 18 years old diagnosed with classic cMPN: PV, ET, and primary myelofibrosis (PMF) from 2015 to 2024 according to the 2022 WHO criteria. Patients with UA levels at diagnosis and prior to treatment initiation for cMPN were included exclusively. Hyperuricemia was defined as UA levels ≥ 7 mg/dL. The time calculated for thrombotic events was from diagnosis until the thrombosis events. We included different types of thromboses as the following: Thromboses in unusual sites: StrokeSplanchnic thrombosis: Budd-Chiari syndrome, portal vein thrombosis, mesenteric thrombosis;Venous thromboses: splanchnic thrombosis and deep vein thrombosis (DVT)Arterial thromboses: acute myocardial infarction and stroke.
RESULTS
A total of 100 patients with cMPN met the inclusion criteria, female was the predominant gender. 60% were diagnosed with PV (77.6% high risk), 9% with ET (44.4% very-low risk), and 31% with PMF (35.5% intermediate-high risk). The mean age was 55.4 ± 15.7; 47.9 ± 20.2; and 58.5 ± 14.1 years, respectively.
50% of patients had elevated UA levels at diagnosis, mostly in men (62%) and ≥60 years old (64%). Non-significant differences were shown in thrombotic events between patients with normal UA levels and those with hyperuricemia. Table 1 shows the main baseline characteristics of the population with myeloproliferative neoplasms based on the presence of hyperuricemia.
In our Cox model shown in Table 2 PV and ET presented a higher risk of thrombosis compared to PMF. Hyperuricemia at diagnosis was not associated with a higher risk of thrombotic events.
CONCLUSIONS
No study has demonstrated hyperuricemia as a risk factor for thrombosis among the three classic cMPN to date. The studies known in the literature that provide an analysis of hyperuricemia association with higher risks of thrombosis and death were made between PV and ET, or searching for individual outcomes in PMF. However in our analysis, we aimed to compare the relationship of hyperuricemia with thrombosis risk among the three types of cMPN, where a non-significant difference was observed in thrombotic events between those with hyperuricemia compared to those with normal UA levels. There is an unmet need to explore other risk factors that would influence the high rate of thrombosis present in these neoplasms in addition to the already known risk factors.