Abstract Body (Do not enter title and authors here): Background
Bleeding risk is a major concern for patients receiving transcatheter aortic valve implantation (TAVI) due to heparin use. In recent studies, Heparin antagonists, such as protamine, have shown potential in mitigating this complication. We aim to evaluate its potential role in reducing the risk of bleeding in patients post-TAVI.

Methods
On March 18, 2024, related articles were searched in the following databases: PubMed, Embase, Scopus, Web of Science, Cochrane Library, Wiley Library, VHL, Google Scholar, and clinicaltrials.gov. The inclusion criteria consisted of studies that reported the use of protamine in patients who underwent TAVI, with the aim of reducing bleeding risk compared to administering a placebo or no treatment. Our primary outcomes included major bleeding, life-threatening bleeding, the need for blood transfusion, the 30-day mortality rate, and any events of stroke or transient ischemic attack (TIA). The effect size was calculated using the odds ratio with a 95% confidence interval. Meta-analysis was conducted based on random-effect model using Revman.

Results
Out of the 14,705 articles we obtained, only 5 papers were included. One was a randomized controlled trial; the remaining 4 were observational cohorts with control groups. These studies comprised a total of 3,502 patients. Protamine significantly reduced major bleeding (OR 0.44, 95% CI 0.29-0.69, p = 0.0003, I² = 37%), especially with full-dose administration (1 mg/100 U UFH) compared to partial-dose administration (0.5 mg/100 U UFH) (OR 0.38, 95% CI 0.25-0.58, p < 0.00001, I² = 0%). Similarly, protamine significantly reduced life-threatening bleeding (OR 0.37, 95% CI 0.20-0.67, p = 0.001, I² = 4%), particularly with full-dose usage compared to partial-dose (OR 0.37, 95% CI 0.18-0.73, p = 0.004, I² = 0%). However, no significant difference was observed in the need for blood transfusion (OR 0.75, 95% CI 0.46-1.24, p = 0.27, I² = 33%), stroke/TIA risk (OR 0.82, 95% CI 0.41-1.61, p = 0.56, I² = 49%), or 30-day mortality (OR 0.93, 95% CI 0.62-1.39, p = 0.73, I² = 0%).

Conclusions
The use of protamine appears to significantly reduce major and life-threatening bleeding. The need for blood transfusion, risk of stroke or TIA, and 30-day mortality did not show significant differences. These findings suggest that protamine may be an effective intervention for reducing bleeding complications post-TAVI. However, large randomized controlled trials are needed to validate these findings.