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Influence of Direct Oral Anticoagulant Levels and Thrombin Generation on Postoperative Bleeding [SONAR]: A Nested
Joseph R Shaw1, Na Li2,3, Matthieu Grussé4
1Department of Medicine, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Thrombosis and Haemostasis
|January 21, 2025
Summary
Direct oral anticoagulants (DOACs) can increase surgical bleeding risk. Even low residual DOAC levels impact thrombin generation, a key factor in bleeding after surgery.
Area of Science:
- Pharmacology
- Hematology
- Surgical hemostasis
Background:
- Direct oral anticoagulants (DOACs) are widely used but their impact on surgical bleeding is not fully understood.
- A specific concentration threshold for DOACs that affects surgical hemostasis remains unknown.
- Thrombin generation assays (TGAs) offer a method to assess coagulation phenotype.
Purpose of the Study:
- To investigate the association between preoperative TGA parameters and postoperative bleeding in patients on DOACs.
- To determine if residual DOAC levels contribute to this association.
- To explore the mediating role of TGA parameters in DOAC-related bleeding.
Main Methods:
- A nested case-control study utilizing samples from the PAUSE perioperative study.
- Measurement of DOAC levels via chromogenic anti-Xa assay.
- Assessment of TGA parameters using calibrated automated thrombography.
- Statistical analysis including generalized linear mixed models and causal mediation analyses.
Main Results:
- Residual DOAC levels were significantly higher in patients who experienced postoperative bleeding (cases) compared to controls.
- All TGA parameters correlated with residual DOAC levels.
- Increased lag time and time-to-peak in TGA were associated with higher odds of bleeding.
- Higher peak thrombin and mean velocity rate index were associated with lower odds of bleeding.
- Causal mediation analysis confirmed that TGA parameters mediate the effect of DOACs on bleeding.
Conclusions:
- Low residual DOAC levels measurably impact thrombin generation.
- Altered thrombin generation parameters are a significant factor in DOAC-related bleeding.
- These findings highlight the complex interplay between DOACs, coagulation dynamics, and surgical bleeding risk.
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