Assessment of acquired activated protein C resistance with the FibWave and comparison with the ETP-based APC resistance

Abstract

Introduction: Activated protein C (APC) resistance is a major risk factor of venous thrombosis which may be acquired by hormonal therapy or other causes. The FibWave, a sensitive global clot-based assay design to analyze the coagulation kinetics in plasma, may be a good candidate to assess this prothrombotic state. This study aims to assess the suitability of the FibWave to differentiate the coagulation kinetics of women on oral contraceptives.

Materials and methods: Fifty-four healthy volunteers were divided into 5 groups: men [n = 13], women not using hormonal contraception [n = 12], women using second [n = 12] or third generation [n = 12] combined oral contraceptives, and women using progestin only contraceptive [n = 5]. Patients with coagulation abnormalities were also assessed [n = 8]. The APC resistance was assessed on the FibWave using exogenous APC or Protac, and on the Calibrated Automated Thrombogram using the ETP-based APC resistance assay.

Results: Either in presence or in absence of APC or Protac, the FibWave was able to detect a hypercoagulable state in plasma samples. All combined oral contraceptives showed a lower FW-Max₁ , FW-Max_2, and FW-Min₂ percentage of inhibition and a lower FW-Ttpeak ratio than the other groups. The sensitivity of the FibWave was similar to the one of the ETP-based APC resistance assay.

Conclusion: The FibWave is able to differentiate APC resistance levels observed in women on combined oral contraceptive. The FW-Max₁ , FW-Max_2, and to a lesser degree FW-Min₂ were identified as the most sensitive parameters with a similar performance to the ETP-based APC resistance assay.

Keywords: activated protein C resistance; blood coagulation tests; clot waveform; contraceptive agents; thrombin generation.