Effect of PCC on thrombin generation in patients on FXaI with bleeding or needing urgent surgery (GAUGE).

Prothrombin complex concentrates (PCC) are used off-label to treat direct factor Xa inhibitor (FXaI)-associated bleeding or to optimize hemostasis before urgent surgery. The Global Assessment of Hemostatic TGA Indices Following the Use of Prothrombin Complex Concentrates for Major Bleeding or Urgent Surgery in Patients Treated with Factor Xa Inhibitors (GAUGE) study is a prospective observational cohort study of the effects of PCC on thrombin generation and hemostasis in FXaI-treated patients. FXaI-treated patients who presented with major bleeding or needed urgent surgery received PCC (50 IU/kg). Platelet-poor plasma was collected before and after PCC administration. Thrombin generation assay parameters, including lag time (LT), time to peak (TTP), peak thrombin generation (peak), endogenous thrombin potential (ETP), and mean velocity rate index (mVRI) 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). The median PCC dose was 48.0 IU/kg (interquartile range [IQR], 42.0-50.0). PCC did not affect FXaI levels (P> .05). PCC increased ETP (Δ868.9 ± 766.6 nM/min), peak (Δ85.7nM ± 108.2nM), and mVRI (Δ16.5 nM/min [IQR, 4.4-45.0]). PCC did not affect the LT or TTP (P> .05). Patients in cluster 1 had significantly lower pre-PCC FXaI levels (79 ng/mL [IQR, 55-93] vs 165 ng/mL [IQR, 77-219]; P = .009) and a greater ΔETP increment (P< .0001) than patients in cluster 2. Effective hemostasis was achieved in 50.0% of major bleeding events (95% confidence interval [CI], 38.4-61.6), and procedural hemostasis was normal in 76.7% of urgent surgeries (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.