Risk of thrombotic and bleeding events in patients with MPNs - does SSRI use have an impact?

Abstract Background: Myeloproliferative neoplasms (MPNs) are associated with an elevated risk of thrombotic and hemorrhagic complications. Selective serotonin reuptake inhibitors (SSRIs), commonly prescribed for major depressive disorder and various anxiety disorders, exert a dual effect on platelet function, displaying both prothrombotic and pro hemorrhagic tendencies. However, their impact on vascular outcomes in patients with concomitant MPNs remains unclear. The current study examines the association between SSRI use and the risk of thrombotic and bleeding events in patients with MPNs. Methods: We conducted a retrospective, propensity matched study using the TrinetX network database. Patients >18 years of age, diagnosed with any of the following MPNs: Polycythemia Vera (PV), Essential Thrombocythemia (ET), or Primary Myelofibrosis (PMF) were included. The cohorts were then compared between MPN patients prescribed SSRIs after this diagnosis to those who were never on SSRIs. Patients who were ever prescribed Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) were excluded. Propensity score matching was applied to match demographics and comorbidities. The primary outcomes were all-cause mortality and risk of thrombotic events like deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI). Secondary outcomes were risk of gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). Results: Propensity score-matching resulted in 10,920 patients in each group, with MPNs, with and without SSRI use respectively. All-cause mortality was higher in those with SSRI use, Hazard Ratio 1.094, (95% CI 1.006, 1.19). The risk of thromboembolism was higher in those with SSRI use: venous thromboembolism, OR 1.968 (1.666, 2.324), PE, OR 2.225 (1.754, 2.824), Stroke OR 3.019 (2.556, 3.566) and MI OR 2.72 (2.288, 3.233). The risk of bleeding was as follows: GI bleeding OR 2.123 (1.877, 2.401) and ICH OR 2.893 (2.268, 3.691). Conclusion: The current study suggests that SSRI use in patients with MPNs is significantly associated with increased risk of thrombosis and bleeding, particularly stroke and ICH. SSRIs predispose to thrombosis by transiently elevating serotonin levels, causing a pro inflammatory state, impaired fibrinolysis, and vascular endothelial dysfunction. However, with chronic use, SSRIs can deplete intraplatelet serotonin levels, impairing platelet aggregation causing an increased risk of bleeding, especially in conjunction with antiplatelet or cytoreductive agent use. Given the high prevalence of SSRI use, our study underscores the need for further prospective studies, heightened clinical vigilance when prescribing SSRIs in patients with MPNs and potential consideration of alternate agents, using individualized treatment strategies.