Thrombosis May Increase Risk of Cardiovascular Disease, Secondary Cancers in Myeloproliferative Neoplasms

Researchers have found associations between arterial and venous thrombosis and mortality, disease progression, cardiac events, and second cancers (SC) in myeloproliferative neoplasms (MPNs). The data, published in Blood Cancer Journal, suggest that common inflammatory pathways driving disease progression in MPNs could influence cardiovascular disease (CVD) and cancer incidence.¹

3D rendering of thrombosis in an artery | Image Credit: © Matthieu - stock.adobe.com

MPNs are clonal illnesses of the bone marrow and blood cells that are distinguished by aberrant hematopoietic growth. The World Health Organization has divided MPNs into 8 subclasses, but the 4 traditional kinds are essential thrombocythemia (ET), primary myelofibrosis (PMF), polycythemia vera (PV), and chronic myeloid leukemia. Each of these subtypes has its own unique morphology, symptoms, and diagnosis.²

Treatment of MPNs has evolved with the development of Janus kinase (JAK) inhibitors, targeting mutations such as JAK2 V617F, which are found in over 95% of PV and approximately 60% to 70% of ET and PMF cases. These therapies are aimed at reducing the risk of thrombosis, which is a cause of death and disability.¹

Thrombosis occurs at diagnosis in approximately 20% of MPN cases and remains a significant challenge for patients. In a large study involving 9429 MPN patients and 35,820 matched controls, investigators reported that at 3 months following diagnosis, the hazard ratio (HR) for arterial thrombosis was significantly higher risk compared with the general population. For venous thrombosis, the HR was even more pronounced at 9.7. By the 1-year mark, the HRs demonstrated a decline, with arterial thrombosis at 2.0 and venous thrombosis at 4.7. After 5 years, the trend continued, showing an arterial HR of 1.5 and a venous HR of 3.2.¹

The frequency of thrombotic events also differs in MPNs during follow-up. In PV, ET, pre-PMF, and PMF, the rates of thrombosis are 19%, 12%, 15%, and 7%, respectively. Among patients with PV who develop thrombosis, data shows that the probability of death within the first 10 years is about 40%, which is twice the rate (20%) observed in patients without thrombosis (P < .01). This mortality risk was notably higher for arterial thrombosis compared with venous events (HR for arterial thrombosis = 1.74; P < .01). In ET, the presence of thrombosis correlated with a 25% increase in mortality risk, with arterial events being 70% more common than venous thromboembolism (VTE).¹

The authors point specifically to multiple consequences that may be associated with thrombosis in patients with MPN, including disease progression, SCs, and CVD. In a study of patients with PV and ET, thrombosis was found to significantly increase the risk of progression to MF and the blast phase. The transition to MF was direct in 85% of cases, with 15% progressing due to thrombosis.¹

When looking at risk of cancer, investigators cited a case-controlled study that identified arterial thrombosis in MPN patients younger than 60 years as an independent predictor of SC, with an HR of 2.53. Venous thrombosis showed a non-significant trend (HR = 1.78). In a separate study, the incidence of SCs following arterial thrombosis was 8.5% and 4.9% for VTE, suggesting that arterial thrombosis may be more predictive of SC development.¹

The authors point specifically to the influence of inflammatory pathways, which may explain the underlying mechanisms driving the development of CVD and SCs in MPNs.¹

“Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), are associated with the aggressiveness of [PV] and [ET], linking thrombosis to SC risk,” the authors wrote. “This suggests a common inflammatory pathway likely influencing [CVD] and cancer incidence. Notably, this is observed more frequently in younger patients, likely due to prolonged exposure to MPN and environmental inflammatory triggers.”¹

The occurrence of thrombosis in patients with MPNs is not only common but also serves as a critical indicator of disease severity and is associated with an increased risk of progression to more severe disease states. Given the intricate relationships between thrombosis and SCs, CVD, and worsening disease, comprehensive monitoring of patients is crucial. The findings emphasize the need for new therapeutic strategies aimed at targeting the inflammatory mechanisms involved in thrombus formation, along with standard treatments for MPNs.

REFERENCES

1. Barbui T, Ghirardi A, Carobbio A, et al. Thrombosis in myeloproliferative neoplasms: a viewpoint on its impact on myelofibrosis, mortality, and solid tumors. Blood Cancer Journal. October 25, 2024. Doi:10.1038/s41408-024-01169-6

2. New model can assess blast phase progression risk in myeloproliferative neoplasms. Pharmacy Times. November 12, 2024. Accessed April 21, 2025. https://www.pharmacytimes.com/view/new-model-can-assess-blast-phase-progression-risk-in-myeloproliferative-neoplasms