Calibrated automated thrombogram II: removing barriers for thrombin generation measurements

Area of Science:

• Hemostasis and Thrombosis Research
• Clinical Chemistry and Diagnostics
• Pharmacodynamics of Anticoagulants

Background:

• Thrombin generation (TG) via Calibrated Automated Thrombogram (CAT-I) assesses coagulation balance but has limitations.
• CAT-I struggles with substrate consumption and cannot calibrate with direct thrombin inhibitors (DTIs).
• A modified assay, CAT-II, was developed to address these limitations in TG assessment.

Purpose of the Study:

• To compare the performance of the modified TG assay (CAT-II) against the standard CAT-I method.
• To evaluate CAT-II's efficacy with various anticoagulants and interfering substances.
• To assess a new automated TG instrument (ST®-Genesia) using a standardized calibration method.

Main Methods:

• Thrombin generation was measured using CAT-I, CAT-II, and ST®-Genesia in plasma samples.
• Samples included controls, those with dabigatran, rivaroxaban, apixaban, and interfering substances.
• CAT-II and ST®-Genesia utilized a novel calibration method with standard thrombin and AMC in separate plasma.

Main Results:

• CAT-II showed higher TG values than CAT-I in anticoagulant-free plasmas; both methods had <5% intra-assay variation.
• CAT-II accurately detected dose-dependent inhibition by dabigatran, a feat missed by CAT-I.
• Both CAT-II and ST®-Genesia effectively corrected for interfering substances and detected oral anticoagulant effects.

Conclusions:

• The CAT-II method demonstrates high similarity to CAT-I in non-DTI samples.
• CAT-II and ST®-Genesia with the new calibration method reliably detect effects of all oral anticoagulants.
• The improved calibration method in CAT-II significantly enhances monitoring of patients on direct thrombin inhibitors.