Development and Validation of a Predictive Risk Algorithm for Bleeding in Individuals on Long-term Hemodialysis: An International Prospective Cohort Study (BLEED-HD)

BACKGROUND: Individuals with kidney disease are at a high risk of bleeding and as such tools that identify those at highest risk may aid mitigation strategies. OBJECTIVE: We set out to develop and validate a prediction equation (BLEED-HD) to identify patients on maintenance hemodialysis at high risk of bleeding. DESIGN: International prospective cohort study (development); retrospective cohort study (validation). SETTINGS: Development: 15 countries (Dialysis Outcomes and Practice Patterns Study [DOPPS] phase 2-6 from 2002 to 2018); Validation: Ontario, Canada. PATIENTS: Development: 53 147 patients; Validation: 19 318 patients. MEASUREMENTS: Hospitalization for a bleeding event. METHODS: Cox proportional hazards models. RESULTS: Among the DOPPS cohort (mean age, 63.7 years; female, 39.7%), a bleeding event occurred in 2773 patients (5.2%, event rate 32 per 1000 person-years), with a median follow-up of 1.6 (interquartile range [IQR], 0.9-2.1) years. BLEED-HD included 6 variables: age, sex, country, previous gastrointestinal bleeding, prosthetic heart valve, and vitamin K antagonist use. The observed 3-year probability of bleeding by deciles of risk ranged from 2.2% to 10.8%. Model discrimination was low to moderate (c-statistic = 0.65) with excellent calibration (Brier score range = 0.036-0.095). Discrimination and calibration of BLEED-HD were similar in an external validation of 19 318 patients from Ontario, Canada. Compared to existing bleeding scores, BLEED-HD demonstrated better discrimination and calibration (c-statistic: HEMORRHAGE = 0.59, HAS-BLED = 0.59, and ATRIA = 0.57, c-stat difference, net reclassification index [NRI], and integrated discrimination index [IDI] all P value <.0001). LIMITATIONS: Dialysis procedure anticoagulation was not available; validation cohort was considerably older than the development cohort. CONCLUSION: In patients on maintenance hemodialysis, BLEED-HD is a simple risk equation that may be more applicable than existing risk tools in predicting the risk of bleeding in this high-risk population.