Differentiating Pathologic from Physiologic Fibrinolysis: Not as Simple as Conventional Thrombelastography

Area of Science:

• Trauma Hemostasis and Coagulation
• Thromboelastography Applications
• Fibrinolysis Phenotyping

Background:

• Conventional rapid thrombelastography (rTEG) cannot distinguish between fibrinolysis shutdown and hypofibrinolysis due to similar low fibrinolytic activity.
• Tissue plasminogen activator (tPA) TEG can identify depleted fibrinolytic inhibitors, offering a potential to differentiate all three pathological fibrinolytic phenotypes post-trauma.
• Combining rTEG and tPA-TEG may enable more precise stratification of fibrinolysis phenotypes and associated mortality risk.

Purpose of the Study:

• To evaluate the combined utility of rTEG and tPA-TEG in differentiating post-injury fibrinolysis phenotypes.
• To assess the predictive value of these combined assays for mortality risk stratification in trauma patients.
• To determine if combined rTEG and tPA-TEG offer superior mortality prediction compared to individual assays.

Main Methods:

• Included 981 adult trauma patients with rTEG and tPA-TEG performed within 2 hours post-injury.
• Defined initial fibrinolysis phenotypes using rTEG lysis at 30 minutes after maximum amplitude (LY30).
• Utilized Youden Index on tPA-TEG LY30 to define tPA-sensitive (inhibitor depletion) and tPA-resistant phenotypes, creating 9 distinct groups to assess mortality risk.

Main Results:

• The combination of rTEG and tPA-TEG identified 5 of 9 fibrinolytic phenotypes associated with increased mortality.
• tPA-TEG LY30 thresholds of >35.5% (sensitive) and <0.3% (resistant) significantly correlated with increased mortality (OR 9.2 and 6.3, respectively).
• Combined analysis (AUC 0.80) significantly outperformed rTEG (AUC 0.63) and tPA-TEG (AUC 0.75) alone in predicting mortality, allowing condensation into 3 key pathologic phenotypes.

Conclusions:

• The combination of rTEG and tPA-TEG significantly enhances the prediction of mortality in trauma patients.
• This integrated approach allows for better differentiation of complex fibrinolysis phenotypes, including true hyperfibrinolysis, early fibrinolysis shutdown, and hypofibrinolysis.
• Patient-specific strategies informed by combined rTEG and tPA-TEG analysis hold potential for improving trauma patient outcomes.