Altered thrombin generation with prothrombin complex concentrate is not detected by viscoelastic testing: an in vitro study.
Summary
In an ex vivo study using blood from 13 healthy donors, thrombin generation increased after hemodilution and further after 4F-PCC spiking, but viscoelastic clot times (CT/ACT) on four platforms did not reflect this augmentation. Findings challenge algorithms that trigger PCC administration based on prolonged CT/ACT to enhance thrombin generation.
Key Findings
- Thrombin generation parameters (velocity index, peak, endogenous thrombin potential) increased after 50% dilution and further after 4F-PCC spiking (all P<0.01 to <0.001).
- Viscoelastic clot initiation times (CT/ACT) were prolonged by dilution on all four devices but did not improve after 4F-PCC spiking.
- Standard coagulation tests improved after PCC spiking but did not return to baseline.
Clinical Implications
Avoid relying solely on prolonged CT/ACT to trigger PCC in bleeding/hemodilution; integrate thrombin generation or comprehensive coagulation assessment where feasible, and prioritize clinical context.
Why It Matters
This work directly questions a widespread practice of using VET clot times as triggers for PCC in bleeding management, suggesting potential overtreatment or misguidance. It will likely recalibrate transfusion algorithms and prompt validation with outcome studies.
Limitations
- In vitro ex vivo design in healthy donor blood limits clinical extrapolation.
- Sample size is modest (n=13) and lacks patient-centered outcomes.
Future Directions
Prospective clinical studies correlating thrombin generation, VET parameters, PCC dosing, and bleeding outcomes are needed to redefine PCC triggers.
Study Information
- Study Type
- Basic/Mechanistic research
- Research Domain
- Diagnosis
- Evidence Level
- V - Preclinical in vitro experimental study using human whole blood; no patient outcomes.
- Study Design
- OTHER