Blood Transfusion Risk Following Early Versus Delayed Surgery in Hip Fracture Patients on Direct Oral Anticoagulants: A Study Protocol for a Natural Experiment

<b>Background</b>: Early surgical intervention is associated with improved outcomes in hip fracture care, yet in patients using Direct Oral Anticoagulants (DOACs), surgery is frequently delayed due to concerns about increased intraoperative bleeding. Despite the increasing prevalence of hip fracture patients on DOACs, no consensus exists on optimal surgical timing. This has led to substantial practice variation between hospitals, with some operating within 24 h of last DOAC intake and others delaying surgery beyond 24 h. This study hypothesizes that early surgery within 24 h results in a non-inferior blood transfusion risk compared to delayed surgery 24 h or more after last DOAC intake in hip fracture patients on DOACs. This protocol describes the design and methodological rationale of a natural experiment. <b>Methods and analysis</b>: A multicenter cohort study designed as a natural experiment will be conducted across seven Dutch level 2 trauma centers, using predefined and standardized prospectively collected variables from electronic health records. Centers will adhere to distinct local surgical timing protocols, forming two cohorts: early surgery within 24 h and delayed surgery 24 h or more after last DOAC intake. Patients presenting with an isolated hip fracture who are using a DOAC and have taken their last dose within 24 h before admission will be included. The primary endpoint is postoperative blood transfusion. Secondary endpoints include additional bleeding-related outcomes, thrombotic and postoperative complications, and hospital length of stay. The primary analysis will be conducted on a per-protocol basis, with an intention-to-treat analysis performed as a supplementary assessment. Non-inferiority will be established if the upper bound of the one-sided 95% confidence interval for the risk difference does not exceed the predefined margin of 5%. <b>Ethics and dissemination</b>: Ethical approval was obtained from the Medical Ethics Committee United, Utrecht, The Netherlands. As this is a cohort study without altering clinical care, individual informed consent is not required. All data will be pseudonymized, and findings will be disseminated through peer-reviewed journals and scientific conferences. <b>Registration details</b>: Medical Ethics Committee United, Utrecht, The Netherlands, registration number W25.034.