The effect of excessive anticoagulation on mortality and morbidity in hospitalized patients with anticoagulant-related major hemorrhage

Background: We aimed to determine the effect of excessive anticoagulation on morbidity and mortality in hospitalized patients with major anticoagulant-associated hemorrhage. Methods: We prospectively identified 10 1 consecutive inpatients admitted to Brigham and Women's Hospital with major bleeding occurring during administration of warfarin sodium, unfractionated heparin (UFH), or low-molecular-weight heparin (LMWH). Results: Fifty patients had excessive and 51 had non-excessive anticoagulation. The overall mortality at 60 days was 26% (13/50) in the excessive group compared with 10% (5/51) in the nonexcessive group (P=.03). Excessive warfarin therapy was associated with an increased 60-day mortality (P=.049), in contrast to excessive anticoagulation with UFH or LMWH alone (P=.27) or UFH or LMWH as a "bridge" to warfarin therapy (P=.10). Multivariate regression identified excessive anticoagulation as an independent predictor of 60-day mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 1.39-12.49; P=.01), along with intracranial hemorrhage (adjusted HR, 6.16-195% CI, 1.75-21.67; P=.005) and active cancer (adjusted HR, 3.79; 95% CI, 1.13-12.70; P=.03). Excessive anticoagulation was also a significant predictor of the combined nonfatal end point of stroke, myocardial infarction, hypotension, critical anemia, and surgical or angiographic intervention at 30 days (HR, 2.17; 95% CI, 1.25-3.78; P=.006). Conclusion: In a cohort of patients with anticoagulation-associated hemorrhage, excessive anticoagulation contributed independently to increased morbidity and mortality.