Major Bleeding Post-Renal Transplant in Anticoagulated Patients: A Retrospective Cohort Study
Authors: Shweikialrefaee Bisan , Kim Joseph , Famure Segun , Abdulrehman Jameel 
Published: December 2024

Background:

Renal transplantation (RT) is the preferred treatment for end-stage kidney disease, but is associated with a high risk of bleeding, particularly in patients on chronic anticoagulation (AC). Peri-procedural AC management is challenging, as early resumption may decrease the thrombosis risk but could increase the bleeding risk. Unfortunately, data regarding the effect of peri-procedural AC on bleeding outcomes in RT is very limited.

Objectives:

The primary objective was to describe the risk of major bleeding (MB) in patients on chronic AC and not on chronic AC.

The secondary objectives were (1) to identify patient characteristics associated with MB (2) to describe the following risks, and specifically based on post-RT (PRT) day AC restart in those on chronic AC (i) MB (ii) thrombosis (iii) graft loss (iv) all-cause mortality.

Methods:

This is an interim analysis of a single center retrospective cohort study included consecutive adult RT patients from June 01, 2011, to June 30, 2020. Patients with known congenital bleeding disorders, multiple organ transplant, and previous RT were excluded. Patients were identified through the Comprehensive RT Research Information System and the Organ Transplant Tracking Record databases. Baseline characteristics and study outcomes were collected from the database and the electronic patient record.

Patients were followed for outcomes from day 0 to 30 PRT. The AC group included those on chronic therapeutic AC who were restarted on AC within 30 days PRT and does not include AC intended solely for VTE prophylaxis. MB was defined as per a modified International Society on Hemostasis and Thrombosis criteria. Thrombosis included both arterial thromboembolism (ATE) and VTE. Graft loss was defined as graft failure requiring renal replacement therapy.

Baseline characteristics and outcomes were summarized using descriptive statistics.

Results

From 800 patients screened, 590 patients met eligibility criteria and were included in the study. The median age was 52 (standard deviation 13.8) years and 242 (41%) were female. The majority of RT were from a deceased donor (n=369, 62.5%). Prior MB and thrombosis occurred in 36 (6.1%) and 28 (4.7%) respectively. Approximately a quarter of patients (n=167, 28.3%) were on antiplatelet therapy prior to RT.

Twenty-four (4.1%) were on AC prior to RT, however, only 21 (3.6%) patients were restarted on AC within 30-day PRT and were included in the AC group. The most common AC PRT was warfarin (n=17, 80.1 %), followed by LMWH (n=2, 9.5%) and direct oral AC (n=2, 9.5%), and the most common AC indication was atrial fibrillation (n=10, 47.6%) followed by VTE (n=8, 38.1%%). AC was restarted in the AC group on the following days: 7 patients &lt; 3 days PRT, 10 patients on days 4 to 7 PRT, and 4 patients after day 7 PRT.

Eight (38.1.% (95% confidence interval (CI) 21.8 to 59.1)) in the AC group had MB, compared to 146 (25.7% (95% CI 22.2 to 29.4)) in the no AC group. The most common types of MB in the AC and no AC groups were renal (n=4 (50%) and n=85 (58.2%)), and no identified source (n=3 (37.5%) and n=48 (32.9%)), respectively.

Among all patients with MB, 78.6% (95% CI 71.4 to 84.3) had hypertension, 51.3% (95% CI 43.5 to 59.1) were male, 36.4% (95% CI 29.2 to 44.2) had diabetes, and 33.8% (95% CI 26.8 to 41.6) were on antiplatelet therapy.

In the AC group, prior to restarting AC, four patients had MB on days 0, 1, 4 and 10 and were later restarted on AC on days 10, 4, 5 and 14 respectively. The rest of the MB in the AC group occurred after restarting AC on days 2, 3, 5 and 7 with MB on days 8, 9, 10 and 10 respectively.

One (4.8 % (95% CI 0.8 to 22.7)) of the patients in the AC group developed thrombosis, a VTE on day 13 PRT, on subtherapeutic warfarin (INR= 1.34). Twenty (3.5 % (95% CI 2.3 to 5.4)) patients in the no AC group had thrombosis, including 17 (85%) VTE and 3 (15 %) ATE. There was no graft loss or mortality in the AC group, but 2 (0.4 % (95% CI 0.1 to 1.3)) and 3 (0.5% (95% CI 0.2 to 1.5)) in the no AC group respectively

Conclusion

MB is common PRT, especially in those on chronic AC. Patients on chronic AC may be high bleeding risk at baseline, even prior to restarting AC PRT. Prospective data is needed to devise evidence-based strategies to guide peri-RT AC.