Activated protein C is a sensitive biomarker to monitor the activity level of the hemostatic system after activation by recombinant activated factor VII

H. Rühl, C. Berens, F. I. Winterhagen, J. Müller, J. Oldenburg, B. Pötzsch (Bonn, Germany)

Innovation and Novelty
Date: 16.02.2017,
Time: 14:00 - 15:15

Objective: Evaluation of the activity level of the hemostatic system using current biomarkers is difficult due to their high interindividual variation, low specificity, or long persistence in circulation. Objective of our study was to monitor the activation status of coagulation by measuring plasma levels of free thrombin and activated protein C (APC) using a highly sensitive oligonucleotide-based enzyme capture assay (OECA) platform.

Methods: In order to induce a standardized and limited activation of the clotting cascade, recombinant, activated factor VII (rFVIIa) was injected i.v. into 10 healthy volunteers (6 females) at a dose of 15 µg/kg bodyweight. Plasma levels of FVIIa and of hemostasis-related biomarkers including free thrombin, APC, the prothrombin activation fragment F1+2, thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin complex (PAP), and D-dimer were determined at baseline and repeatedly during a 24 h lasting follow-up period.

Results: rFVIIa was well tolerated, and its elimination kinetics showed an expected course in all probands. While APC plasma levels lay below the lower limit of quantification at baseline in all subjects, a highly significant increase of APC (median; interquartile range) was observed after 10 min (0.16 (0.12-0.17) ng/mL, p = 0.003), 30 min (0.19 (0.15-0.20) ng/mL, p = 0.005), 60 min (0.16 (0.15-0.20 ng/mL, p = 4x10^-5), and 120 min (0.13 (0.12-0.18) ng/mL, p = 7x10^-4). F1+2 slightly increased from 0.13 (0.10-0.21) nmol/L at baseline to 0.16 (0.11-0.23) nmol/L after 60 min, 0.18 (0.13-0.20) nmol/L after 120 min, and 0.18 (0.13-0.20) nmol/L after 180 min, but these changes lost statistical significance after correction for multiple testing. No significant changes of plasma levels of free thrombin, TAT, PAP and D-dimer were observed.

Conclusion: Among the biomarkers evaluated in this study, APC appears to be best suited to estimate the activation status of the hemostatic system. Our results warrant further studies to evaluate its use in clinical situations of coagulation activation.