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Volume 15
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10.3390/jcm15020758
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Tim Schiepers
1,2,*,
Diederik Smeeing
3,
Hugo Wijnen
4,
Hanna Willems
5,
Frans Jasper Wijdicks
6,
Elvira Flikweert
7,
Diederik Kempen
8,
Eelke Bosma
9,
Johannes H. Hegeman
10,
Marielle Emmelot-Vonk
2,
Detlef van der Velde
1 and
Henk Jan Schuijt
1,5,*
1
Department of Trauma Surgery, St. Antonius Hospital, 3543 AZ Utrecht, The Netherlands
2
Department of Geriatrics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands
3
Department of Trauma Surgery, Rijnstate Hospital, 6800 TA Arnhem, The Netherlands
4
Department of Geriatrics, Rijnstate Hospital, 6800 TA Arnhem, The Netherlands
5
Internal Medicine and Geriatrics, Amsterdam UMC Location, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
6
Department of Trauma Surgery, Diakonessenhuis Hospital, 3508 TG Utrecht, The Netherlands
7
Department of Trauma Surgery, Deventer Hospital, 7416 SE Deventer, The Netherlands
8
Department of Orthopedic Surgery, OLVG Hospital, 1091 AC Amsterdam, The Netherlands
9
Department of Trauma Surgery, Martini Hospital, 9728 NT Groningen, The Netherlands
10
Department of Trauma Surgery, ZGT Hospital, 7609 PP Almelo, The Netherlands
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2026, 15(2), 758; https://doi.org/10.3390/jcm15020758
Submission received: 23 December 2025 / Revised: 13 January 2026 / Accepted: 15 January 2026 / Published: 16 January 2026
(This article belongs to the Special Issue Challenges and Solutions in Geriatric Fracture)
Review Reports Versions Notes

Abstract

Background: 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. Methods and analysis: 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%. Ethics and dissemination: 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. Registration details: Medical Ethics Committee United, Utrecht, The Netherlands, registration number W25.034
Keywords: hip fracture; anticoagulants; blood transfusion; natural experiment; time to treatment; treatment outcome; postoperative complications hip fracture; anticoagulants; blood transfusion; natural experiment; time to treatment; treatment outcome; postoperative complications

Share and Cite

MDPI and ACS Style

Schiepers, T.; Smeeing, D.; Wijnen, H.; Willems, H.; Wijdicks, F.J.; Flikweert, E.; Kempen, D.; Bosma, E.; Hegeman, J.H.; Emmelot-Vonk, M.; et al. Blood Transfusion Risk Following Early Versus Delayed Surgery in Hip Fracture Patients on Direct Oral Anticoagulants: A Study Protocol for a Natural Experiment. J. Clin. Med. 2026, 15, 758. https://doi.org/10.3390/jcm15020758

AMA Style

Schiepers T, Smeeing D, Wijnen H, Willems H, Wijdicks FJ, Flikweert E, Kempen D, Bosma E, Hegeman JH, Emmelot-Vonk M, et al. Blood Transfusion Risk Following Early Versus Delayed Surgery in Hip Fracture Patients on Direct Oral Anticoagulants: A Study Protocol for a Natural Experiment. Journal of Clinical Medicine. 2026; 15(2):758. https://doi.org/10.3390/jcm15020758

Chicago/Turabian Style

Schiepers, Tim, Diederik Smeeing, Hugo Wijnen, Hanna Willems, Frans Jasper Wijdicks, Elvira Flikweert, Diederik Kempen, Eelke Bosma, Johannes H. Hegeman, Marielle Emmelot-Vonk, and et al. 2026. "Blood Transfusion Risk Following Early Versus Delayed Surgery in Hip Fracture Patients on Direct Oral Anticoagulants: A Study Protocol for a Natural Experiment" Journal of Clinical Medicine 15, no. 2: 758. https://doi.org/10.3390/jcm15020758

APA Style

Schiepers, T., Smeeing, D., Wijnen, H., Willems, H., Wijdicks, F. J., Flikweert, E., Kempen, D., Bosma, E., Hegeman, J. H., Emmelot-Vonk, M., van der Velde, D., & Schuijt, H. J. (2026). Blood Transfusion Risk Following Early Versus Delayed Surgery in Hip Fracture Patients on Direct Oral Anticoagulants: A Study Protocol for a Natural Experiment. Journal of Clinical Medicine, 15(2), 758. https://doi.org/10.3390/jcm15020758

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