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Background:

Polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are Philadelphia-negative myeloproliferative neoplasms (MPN). These relatively rare hematologic malignancies are characterized by clonal hematopoiesis. Patients with MPN have an increased risk of vascular complications, including both arterial and venous thrombosis, as well as hemorrhagic events. The objective of study I was to determine the frequency of elevated blood counts among patients presenting with thromboembolic events and to evaluate whether underlying etiologies influence the risk of recurrence. Studies II–IV examined treatment patterns, assessed the incidence and risk factors for arterial and venousthrombosis, major bleeding, and all-cause mortality (ACM) in patients diagnosed with PV, ET, and MF.

Methods and material:

Study I included all adult patients diagnosed with different subtypes of arterial and venousthrombosis thrombosis in the county of Norrbotten during 2017–2018.The cohort used in studies II–IV consists of all adult patients diagnosed with PV, ET, or MF who were registered in the Swedish MPN Register between 1 January 2008 and 29 December 2021, along with a matched control cohort randomly selected from the Population Register by Statistics Sweden. By linking several Swedish healthcare registries, data on clinical outcomes, treatment patterns, and mortality were obtained.

Results:

Among the 3931 patients included in study I, 30.4% of the patients had elevated blood values fulfilling the 2016 revised WHO diagnostic thresholds for PV or ET. Of these, 411 patients had no identifiable secondary cause of erythrocytosis or thrombocytosis and therefore required further evaluation to exclude an underlying MPN. Patients with unexplained thrombocytosis and those with secondary erythrocytosis exhibited the highest recurrence rates of thromboembolic events. In study II, patients with PV and ET demonstrated significantly increased rates of venous thromboembolism, major bleeding, and ACM per 100 treatment-years compared with matched controls. Additionally, PV patients experienced higher rates of arterial thrombosis and all-cause stroke than their respective controls. The MF patients included in study III had significantly higher rates of thromboembolic events, major bleeding, and ACM compared with matched controls. Treatment with JAK inhibitors (JAKi), use of low-molecular weight heparin (LMWH), a history of arterial or venous thrombosis, and advanced age were identified as independent predictors of new events. The observed association between JAKi therapy and thrombosis may partly reflect Swedish treatment guidelines, which restrict JAKi use to patients with high or intermediate-2 risk disease. Similarly, LMWH is often used in contexts such as postoperative care and immobilization, potentially contributing to its association with thrombotic events. A prior venousevent, elevated leukocyte count at diagnosis, and JAKi therapy were also associated with an increased risk of major bleeding. In study IV, analysis of treatment strategies in PV and ET revealed that most high-risk patients were treated in accordance with established guidelines. Unexpectedly, a large proportion of low-risk patients also received cytoreductive therapy during follow-up, likely reflecting the transition to high-risk status upon reaching 60 years of age. Older age and leukocytosis at diagnosis were predictors of thrombotic complications, major bleeding, and ACM in both PV and ET. Treatment with HU and interferon (IFN) was associated with reduced ACM, and HU further demonstrated a protective effect against thromboembolism and major hemorrhage.

Conclusions:

Elevated blood values are common among patients presenting with thromboembolic events, and determining the underlying cause is essential for reducing the risk of recurrence. Patients with PV, ET, and MF experience substantially higher rates of thromboembolic events, major bleeding, and ACM compared with matched population controls, and these risks vary across treatment groups. Several risk factors for vascular complications, major bleeding, and ACM in MPN have been identified.