Venous thromboembolism (VTE) is a common complication of traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Low molecular weight heparin (LMWH) is recommended for prophylaxis against VTE after trauma but may increase the risk of progression of intracranial bleeding. Limited evidence exists to guide clinicians regarding the optimal timing of VTE prophylaxis in patients with acute TBI. This randomised controlled trial (RCT) will directly compare the safety and effectiveness of early versus delayed initiation of LMWH in patients with moderate to severe TBI.

The study design is a Bayesian adaptive RCT comparing early (within three calendar days of injury) versus delayed (after study Day 7) VTE prophylaxis with the LMWH, dalteparin. All patients receive sequential compression devices until study Day 8. The co-primary effectiveness outcome is the development of clinically important VTE at study Day 8. The co-primary safety outcome is the development of clinically important intracranial bleeding at study Day 8. Secondary outcomes are mortality and functional outcomes (Glasgow Outcome Scale Extended and EQ-5D) measured at study Days 30 and 180; clinically diagnosed VTE to Day 30 and progression of intracranial bleeding to Day 8.

This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre) and all participating centres. It is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and Health Canada regulatory requirements. We anticipate that the trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of critical care, trauma and neurosurgery. The results of this trial will help guide clinicians aiming to balance the risks and benefits of early anticoagulant prophylaxis after TBI and will inform guideline development.

NCT03559114.

To evaluate the effects of liberal transfusion strategy (trigger haemoglobin ≤90–100 g/L) compared with a restrictive strategy (trigger haemoglobin ≤70–80 g/L) on long-term neurological functional outcome in anaemic adult patients with acute acquired brain injury (ABI).

Systematic review and study-level meta-analysis of randomised controlled trials (RCTs).

MEDLINE, EMBASE, Cochrane from inception to 6 February 2025.

RCTs enrolling patients with acute ABI and anaemia (haemoglobin ≤100 g/L), comparing a liberal vs restrictive transfusion strategy.

Two reviewers independently identified eligible studies, extracted data and assessed risk of bias. We performed random-effects meta-analysis of RCTs and applied Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the certainty of evidence. Our primary outcome was an unfavourable neurological functional outcome, using the Glasgow Outcome or modified Rankin scales.

Five trials enrolling 2364 patients with acute ABI and anaemia were included in the primary analysis. Liberal transfusion reduces the risk of unfavourable neurological outcome (risk ratio (RR)=0.89, 95% CI 0.84 to 0.95, high certainty). Liberal transfusion may reduce severe disability (RR=0.82, 95% CI 0.66 to 1.02, moderate certainty), and increase good recovery compared with restrictive transfusion (RR=1.29, 95% CI 0.95 to 1.76, low certainty). We found no difference in the risk of most adverse events, including death. Statistical heterogeneity was low (I²=0%–36%) for neurological outcomes.

In adults with acute ABI and anaemia, liberal transfusion reduces the risk of unfavourable outcome (high certainty) and possibly improves the chances of good recovery (low certainty) when compared with restrictive transfusion.

CRD42025628732.