Thrombosis, Major Bleeding Events More Frequent in Myelofibrosis Compared With Other Myeloproliferative Neoplasms

Results of a nationwide Swedish population-based study indicate that patients with myelofibrosis (MF) have increased rates of thromboembolic events and major bleeding compared with presentations in other myeloproliferative neoplasms (MPN), with thromboembolic complications and major bleeding events diverging based on varying treatment groups. These results, published by study authors in Blood Advances, can help health care providers more effectively care for patients with MF, allowing them to counsel patients on associated bleeding risks.¹

Thrombosis can be a deadly complication in patients with myelofibrosis. | Image Credit: © Matthieu - stock.adobe.com

The clinical presentation of MF evolves throughout the development of the disease, eventually presenting as bone marrow fibrosis, hepatosplenomegaly, fatigue, and progressive pancytopenia, ultimately leading to reduced patient quality of life and heightened morbidity. Bleeding and thromboembolic events have been known to be possible complications of MF, but literature on this association is lacking. According to the present investigators, studies analyzing this association are plagued by small cohorts, seldom-included control patients, and populations containing varying MPNs, rather than MF specifically.^2,3

To fill the present gaps in literature regarding thromboembolic and bleeding event prevalence in patients with MF, the current study authors conducted a nationwide analysis to assess the frequency of arterial and venous events, major bleeding, all-cause stroke, and all-cause mortality in Swedish patients with primary MF (PMF) and secondary MF (SMF) compared with matched controls. They also aimed to investigate if outcomes varied based on the therapy used in MF while attempting to describe relevant risk factors for major bleeding and thromboembolic events among patients with MF.¹

Multiple Swedish registries of patients diagnosed with hematologic malignancies were consulted, with all adult patients registered with a diagnosis of MF from 2008 to 2021 included. In total, 1079 patients with MF and 395 controls were included, with a median age of 72 years at diagnosis. Notably, over a third of the patients (40.7%) had an International Prognostic Scoring System (IPSS) score of intermediate-2 or high risk. Furthermore, mutations were present in many patients enrolled in the study and diagnosed after June 1, 2016, with 53.6% having a JAK2 V617F mutation.¹

Across the follow-up period, 125 arterial and 51 venous events occurred in the MF cohort, with event rates of 2.59 and 1.06 events per 100 patient years, compared with 337 (rate 1.51, HR: 1.73; 95% CI, 1.40-2.12; P < .001) and 86 (rate 0.38, HR: 2.75; 95% CI, 1.95-3.90; P < .001) among the control patients. When patients were divided based on diagnoses of PMF or SMF, rates of arterial and venous events were noticeably higher among patients with SMF compared with PMF. In addition, 80 cases of acute myocardial infarction (rate: 1.66), 40 ischemic strokes (rate: 0.83), and 38 pulmonary emboli (rate: 0.79) were documented in the MF cohort.¹

Rates of major bleeding were also assessed. In MF patients, the major bleeding rate was 2.55 (123 events) compared with 0.68 (152 events) in the control population (HR: 3.87; 95% CI, 2.98-4.79; P < .001). Overall, the cumulative incidence of major bleeding, all-cause stroke, and arterial and venous events was significantly higher in all patients in the MF cohort and especially high in patients with PMF, compared with corresponding controls. These factors contributed to the higher rate of all-cause mortality observed in patients with MF compared with controls.¹

In an important development, the investigators found through multivariable analysis that treatment with Janus kinase (JAK) inhibitors was linked to both an increased risk of arterial or venous events (HR: 2.16; 95% CI, 1.27-3.68, P = .0045) and, as an independent risk factor, an increased risk for major bleeding (HR: 2.04; 95% CI, 1.15-3.63, P = .015). However, the authors note that this development could be explained by Swedish MF treatment guidelines regarding JAK inhibitors and the sources of the data, including a disproportionate number of patients being treated with these therapies.¹

“These findings could be a useful tool in the clinical practice when choosing symptom-directed therapy and concomitant antithrombotic treatment based on each MF patient’s clinical presentation,” the investigators concluded. “Further studies on thromboembolic events and major bleeding during the different therapies used in MF are needed to minimize the risk of disabling and life-threatening complications in MF patients.”¹

REFERENCES

1. Larsson AE, Renlund H, Andreasson BI, et al. Thrombosis, major bleeding, and mortality in 1079 myelofibrosis patients, a matched population-based study. 2025. doi:10.1182/bloodadvances.2025016247

2. Guglielmelli P, Pacilli A, Rotunno G, et al. Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis. Blood. 2017;129(24):3227-3236. doi:10.1182/blood-2017-01-761999

3. Kc D, Falchi L, Verstovsek S. The underappreciated risk of thrombosis and bleeding in patients with myelofibrosis: A review. Ann Hematol. 2017;96(10):1595-1604. doi:10.1007/s00277-017-3099-2