Frail patients who fall and their risk on major bleeding and intracranial haemorrhage. Outcomes from the Fall and Syncope Registry.

BACKGROUND: Major bleeding, and intracranial bleeding specifically, are severe complications related to the use of anticoagulation. To what extent the risk for major bleeding is elevated among frail older people is not well known because they are underrepresented in the randomized clinical trials (RCTs). This study investigates the risk for major bleeding (MB) and intra cranial haemorrhage (ICH) in frail older people who fall. METHODS: All patients 65 years and older visiting the Fall and Syncope Clinic, between November 2011 and January 2020, and underwent a MRI of the brain were eligible. Frailty was assessed with a Frailty Index, based on the accumulation of deficits model. Cerebral small vessel disease was described and evaluated as proposed in the position paper of Wardlaw and colleagues in 2013. RESULTS: 479 patients were included in this analysis. Mean follow-up was 7 years per patient (ranging from 1 month to 8 years and 5 months). 368 patients (77%) were frail. A total of 81 patients used oral anticoagulation (OAC). 17 extracranial MB of which 3 were traumatic and 14 gastrointestinal, and 16 ICH occurred. There was a total of 603.4 treatment years with OAC, and 8 MBs occurred among patients on OAC (bleeding rate 1.32 per 100 treatment years), of which 2 ICHs (bleeding rate 0.33 per 100 treatment years). The risk for extracranial MB was increased by the use of antiplatelet agents (APA) (adjusted OR 6.9, CI 95% 1.2-38.3), and by the use of OAC (adjusted OR 9.8, CI 95% 1.7-56.1). The risk for ICH was only heightened by white matter hyperintensities (WMH) (adjusted OR 3.8, CI 95% 1.0-13.4). The use of APA (adjusted OR 0.9, CI 95% 0.3-3.3) or OAC (adjusted OR 0.6, CI 95% 0.1-3.3) did not elevate the risk for ICH. CONCLUSION: In contrast to common belief, frail patients on OAC with repeated falls show a comparable bleeding rate as in the large RCTs, and the use of OAC did not increase the risk for ICH. However, the number of MBs was low, and of ICHs very low, despite extensive follow-up in this registry.

External validation and updating of prediction models of bleeding risk in patients with cancer receiving anticoagulants.

OBJECTIVE: Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with cancer are lacking. The aim of this study is to predict bleeding risk in anticoagulated patients with cancer. METHODS: We performed a study using the routine healthcare database of the Julius General Practitioners' Network. Five bleeding risk models were selected for external validation. Patients with a new cancer episode during anticoagulant treatment or those initiating anticoagulation during active cancer were included. The outcome was the composite of major bleeding and clinically relevant non-major (CRNM) bleeding. Next, we internally validated an updated bleeding risk model accounting for the competing risk of death. RESULTS: The validation cohort consisted of 1304 patients with cancer, mean age 74.0±10.9 years, 52.2% males. In total 215 (16.5%) patients developed a first major or CRNM bleeding during a mean follow-up of 1.5 years (incidence rate; 11.0 per 100 person-years (95% CI 9.6 to 12.5)). The c-statistics of all selected bleeding risk models were low, around 0.56. Internal validation of an updated model accounting for death as competing risk showed a slightly improved c-statistic of 0.61 (95% CI 0.54 to 0.70). On updating, only age and a history of bleeding appeared to contribute to the prediction of bleeding risk. CONCLUSIONS: Existing bleeding risk models cannot accurately differentiate bleeding risk between patients. Future studies may use our updated model as a starting point for further development of bleeding risk models in patients with cancer.