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Background/Aims: We studied factors influencing colon postpolypectomy bleeding (PPB), with a focus on antithrombotic and anticoagulation therapy. Methods: We conducted a retrospective case-control study of all patients who underwent polypectomy at our tertiary referral center in Italy between 2007 and 2014. Polyp characteristics (number of polyps removed per patient, size, morphology, location, resection technique, prophylactic hemostasis methods) and patient characteristics (age, sex, comorbidities, medication) were analyzed. Results: The case and control groups included 118 and 539 patients, respectively. The two groups differed in the frequency of comorbidities (69% vs. 40%, p=0.001), polyps removed (27% vs. 18%, p=0.02), and use of heparin therapy (23% vs. 1%, p<0.001). A total of 279 polyps in the case group and 966 in the control group were nonpedunculated (69% vs. 81%, p=0.01) and measured ≥10 mm (78% vs. 32%, p=0.001). Multivariate analysis showed that polyps ≥10 mm (odds ratio [OR], 6.1; 95% confidence interval [CI], 2.3–15.5), administration of heparin (OR, 16.5; 95% CI, 6.2–44), comorbidity (OR, 2.3; 95% CI, 1.4–3.9), and presence of ≥2 risk factors (OR, 3.2; 95% CI, 1.7–6.0) were associated with PPB. Conclusions: The incidence of PPB increases with polyp size ≥10 mm, heparin use, comorbidity, and presence of ≥2 risk factors.

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