Results from a retrospective population-based cohort study showed that patients diagnosed with myelofibrosis have an increased risk of venous, but not arterial thromboembolism. These findings were published in the Journal of Thrombosis and Haemostasis.
Of the 3 Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), the latter disease, characterized by replacement of normal bone marrow with fibrosis scar tissue, is least common and associated with the worst prognosis. Furthermore, both PV and ET can progress to secondary myelofibrosis.
Although previous studies have established the increased risk of thromboembolism in patients with PV and ET, less is known about the incidence of arterial and venous thromboembolic events in the setting of either PMF or myelofibrosis secondary to either PV or ET.
This case-control study included 642 patients with myelofibrosis along with 2568 control patients without the disease who were matched according to patient- and disease-specific factors, such as age, sex, and index date (the date on which myelofibrosis was diagnosed). Patient information was obtained from an administrative database that included the electronic medical records of a cohort of more than 1 million adults residing in Israel.
The mean age at which myelofibrosis was diagnosed was 66.5 years. Of the more than 40% of patients with myelofibrosis who underwent genotyping, 64.0% were classified as having disease characterized by JAKV617F. Regarding comorbidities present at the index date, those with myelofibrosis were significantly more likely to have a previous diagnosis of diabetes (P =.042), congestive heart failure (P <.001), cirrhosis (P <.001), chronic obstructive pulmonary disease, (P =.014), chronic renal failure (P <.001), previous thromboembolism (P <.001), previous lymphoma (P =.014), PV (P <.001), and ET (P <.001).
A key finding from this study was that myelofibrosis was associated with an increased risk of venous thromboembolism (hazard ratio [HR], 6.88; 95% CI, 2.02-23.45), but not arterial thromboembolism (HR, 0.94; 95% CI, 0.49-1.77).
Multivariate analyses revealed that the only independent cardiovascular-related predictors of venous thromboembolism in the setting of myelofibrosis were previous venous thromboembolism (HR, 5.73; 95% CI, 1.64-19.95) and atrial fibrillation (HR, 3.47; 95% CI, 1.22-9.81).
Notable characteristics of the 23 venous thromboembolic events occurring in 18 patients with myelofibrosis diagnosed during 5-year follow-up, which included 12 patients without a history of PV or ET, were an increased likelihood of venous thromboembolism detection within the first year following diagnosis of myelofibrosis (n=12), and more frequent occurrence at atypical sites, such as the mesenteric and hepatic veins.
Although risk of arterial thromboembolism was not increased in those with myelofibrosis compared with control patients, age (HR, 1.04; 95% CI,1.002-1.07), smoking (HR, 2.13; 95% CI, 1.11-4.08), hypertension (HR, 2.22; 95% CI, 1.01-4.88), ET (HR, 3.26; 95% CI, 1.55-6.87), and lymphoma (HR, 6.89; 95% CI, 1.61-29.40) were found to be independent predictors of arterial thromboembolism in patients with the disease.
Treatment with a JAK2 inhibitor was not associated with increased risk of either type of thromboembolism in patients with myelofibrosis.
In summarizing these findings, the study authors stated that “myelofibrosis seems to be associated with increased risk of venous thromboembolism but not with arterial thromboembolism. Atypical sites of venous thromboembolism are more frequent in myelofibrosis than controls, and are more likely to occur shortly after diagnosis.”
Saliba W, Mishchenko E, Cohen S, Rennert G, Preis M. Association between myelofibrosis and thromboembolism: a population-based retrospective cohort study [published online February 3, 2020]. J Thromb Haemost. doi: 10.1111/jth.14754