Prothrombin complex concentrates increased quantitative thrombin generation and achieved effective hemostasis in 50.0% (95% CI 38.4-61.6) of FXaI-treated patients with major bleeding.
Cohort (n=101)
Does PCC improve thrombin generation and hemostasis in FXaI-treated patients with major bleeding or needing urgent surgery?
PCC provides a prohemostatic effect by increasing quantitative thrombin generation in FXaI-treated patients, rather than acting as a true reversal agent.
Prothrombin complex concentrates (PCC) are used off-label to treat direct factor Xa inhibitor (FXaI)-associated bleeding or before urgent surgery. GAUGE was a prospective observational cohort study of the effects of PCC on thrombin generation and hemostasis in FXaI-treated patients. FXaI-treated patients with major bleeding or needing urgent surgery received PCC (50 IU/kg). Platelet-poor plasma was collected pre-/post-PCC. TGA parameters (LT=lag time, TTP=time-to-peak, peak, ETP=endogenous thrombin potential, mVRI=mean velocity rate index) were measured using calibrated automated thrombography. Hemostatic efficacy, thromboembolism, and mortality were adjudicated in duplicate. Multivariable log-linear regression was used to evaluate PCC effects on FXaI levels. Unsupervised K-means clustering was used to identify patients with the largest ETP increment. GAUGE included 101 episodes of FXaI-associated PCC use (FXaI-associated bleeding = 71; urgent surgery = 30). Median PCC dosing was 48.0 IU/kg 42.0-50.0. PCC did not affect FXaI levels (p0.05). PCC increased ETP (Δ868.9±766.6 nM·min), peak (Δ85.7 nM±108.2), and the mVRI (Δ16.5 nM/min 4.4-45.0). PCC did not affect the LT or TTP (p0.05). Patients in Cluster 1 had significantly lower pre-PCC FXaI levels (79 ng/mL 55-93 vs 165 ng/mL 77-219; p = 0.009) and a greater ΔETP increment (p 0.0001) than patients in Cluster 2. Effective hemostasis occurred in 50.0% 95%CI 38.4-61.6 of major bleeds; procedural hemostasis was normal in 76.7% 95%CI 59.1-88.2. The 30-day risks of thromboembolism and mortality were 6.9% 95%CI 3.4-13.6 and 12.9% 95%CI 7.7-20.8, respectively. PCC increased quantitative thrombin generation without shortening LT or TTP, supporting a prohemostatic effect rather than true FXaI reversal.
Shaw et al. (Thu,) conducted a cohort in FXaI-associated bleeding or needing urgent surgery (n=101). Prothrombin complex concentrates (PCC) was evaluated on Effective hemostasis in major bleeds (95% CI 38.4-61.6). Prothrombin complex concentrates increased quantitative thrombin generation and achieved effective hemostasis in 50.0% (95% CI 38.4-61.6) of FXaI-treated patients with major bleeding.