Godoy, Alejandro

Myeloproliferative neoplasm (MPN) patients are at risk of splanchnic vein thromboses (SVT). Prior studies have failed to demonstrate a benefit of hydroxyurea therapy in preventing recurrent thrombosis after SVT, but are limited by small sample sizes and inability to account for starting, stopping, or switching of cytoreductive therapies. To better assess the impact of cytoreductive therapy on thrombosis recurrence, we performed a retrospective cohort study of MPN-SVT patients from the international GASTRO-MPN Consortium, treating cytoreductive therapy as a time-dependent covariate. We identified 757 patients, of which 43% were treated with cytoreductive therapy. During a median follow-up of 7.4 years, 256 patients (34%) had thrombosis recurrence; 145 (19%) had SVT extension/recurrence/TIPS thrombosis, 138 (18%) an thrombosis recurrence outside the splanchnic bed (74% were venous). Additionally, 262 patients (35%) experienced clinically relevant bleeding and 170 (22%) died. After adjusting for age, sex, prior thrombosis, timing of MPN diagnosis relative to SVT, anticoagulation initiation within 30 days of SVT diagnosis, MPN type, JAK2 status, other cancers and cirrhosis, cytoreductive therapy was associated with a decreased risk of recurrent thrombosis (HR 0.67 95%CI 0.50-0.89, p=0.01). This was driven by a lower risk of SVT extension/recurrence (HR 0.62 95%CI 0.42-0.90, p=0.01) but not by extra-splanchnic thrombosis recurrence (HR 0.97 95%CI 0.72-1.30, p=0.82). In a subgroup of patients without erythrocytosis/thrombocytosis at initial SVT (n=275), cytoreductive therapy was associated with a HR 0.65 (95%CI 0.40-1.07, p=0.09) for recurrent thrombosis. These data support the use of cytoreductive therapy in MPN-SVT patients to prevent recurrent thrombosis, particularly SVT extension/recurrence.

Abstract Optimal management of anticoagulation for patients with aortic mechanical heart valves (MHVs) receiving vitamin K antagonists (VKAs) undergoing gastrointestinal endoscopic procedures is clinically challenging. Risk of bleeding from an unanticipated polypectomy or biopsy further complicates this issue. Current guidelines on use of bridging with low-molecular-weight heparin (LMWH) for these procedures are based on low-quality evidence. We conducted a subanalysis of a retrospective, multicenter observational study of adult patients with aortic MHVs receiving VKAs who underwent elective gastrointestinal endoscopies (colonoscopy or upper endoscopy). We included patients who underwent the procedure between July 1, 2020, and July 1, 2023, at five centers in Canada and the United States Patients with procedures performed on separate days within a 30-day period were excluded. Efficacy and safety outcomes included thromboembolic events, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) in the 30 days post procedure. A total of 192 endoscopic procedures were analyzed. Median (interquartile range [IQR]) patient age was 66 years (58.2–72.8) and 22% were female. Warfarin was interrupted for 185 procedures (96%). Among these, 119 (64%) received LMWH bridging: 33 (17%) pre-procedure only, 10 (5%) post-procedure only, and 76 (40%) both pre- and post-procedure. Post-procedure LMWH was initiated a median (IQR) of 1 day (1–1) and discontinued 5 days post-procedure (3–8). MB occurred in two patients (1%), CRNMB in two patients (1%), and one death (0.5%) was identified; no thromboembolic events occurred. Prior to propensity score matching (PSM), post-procedure LMWH with or without pre procedure LMWH was associated with the composite outcome of MB and CRNMB (P = 0.034), although not with MB or CRNMB individually. After stepwise regression and PSM analyses, no significant differences in bleeding outcomes were observed between patients who received LMWH bridging and those who did not. Our findings indicate that although adverse thrombotic events were rare and use of post-procedure LMWH bridging was significantly associated with a small absolute increased risk of bleeding, it was not significant after PSM. Larger prospective studies are needed to better inform antithrombotic management guidelines for patients with aortic MHVs undergoing gastrointestinal endoscopy.