Shanshan Du1, Job Harenberg, Sandra Krämer, Roland Krämer, Martin Wehling, Christel Weiss. 1. *Clinical Pharmacology Mannheim, Medical Faculty Mannheim, Ruprecht-Karls University Heidelberg, Mannheim; †Institute of Inorganic Chemistry, Ruprecht-Karls University of Heidelberg, Heidelberg; and ‡Biometry and Statistics, Medical Faculty Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany.
Abstract
BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are approved for several indications for prophylaxis of thromboembolism at fixed oral doses. The analysis of NOAC activity/concentration may be required in special patient populations. Heptest coagulation assay determines both factor Xa and thrombin inhibitors. The objective of investigations is to analyze the effects of both groups of NOACs on this assay. METHODS: The performance of a modified Heptest-STAT clotting assay was compared with specific chromogenic substrate assays for factor Xa (Coamatic, HemosIL) and thrombin (direct thrombin inhibitor assay and S2238 chromogenic assays) for the determination of rivaroxaban, apixaban, and dabigatran in plasma from patients on treatment. RESULTS: For rivaroxaban (n = 74), the concentrations (mean and SD) of Heptest-STAT versus Coamatic and HemosIL assays were 179.3 ± 85.8 ng/mL versus 199.3 ± 105.7 ng/mL and 212.4 ± 115.9 ng/mL (P < 0.0001), and for apixaban (n = 26) 232.8 ± 10.0 ng/mL versus 178.4 ± 64.4 ng/mL (P < 0.0001) and 182.1 ± 73.1 ng/mL (P = 0.0002). For dabigatran (n = 74), the values of Heptest-STAT were 92.3 ± 65.0 ng/mL versus 124.3 ± 85.6 ng/mL (direct thrombin inhibitor assay, P < 0.0001) and 107.5 ± 59.7 ng/mL (S2238 assay, P = 0.0015), respectively. The values of the intraclass coefficient of correlation ranged from 0.64 to 0.91 (Bland-Altman analysis). CONCLUSIONS: The objective of the study was achieved by demonstrating a high correlation of the Heptest-STAT coagulation assay with chromogenic assays for factor Xa inhibiting NOACs and acceptably good correlation with thrombin inhibiting NOACs in plasma samples of patients on treatment.
BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are approved for several indications for prophylaxis of thromboembolism at fixed oral doses. The analysis of NOAC activity/concentration may be required in special patient populations. Heptest coagulation assay determines both factor Xa and thrombin inhibitors. The objective of investigations is to analyze the effects of both groups of NOACs on this assay. METHODS: The performance of a modified Heptest-STAT clotting assay was compared with specific chromogenic substrate assays for factor Xa (Coamatic, HemosIL) and thrombin (direct thrombin inhibitor assay and S2238 chromogenic assays) for the determination of rivaroxaban, apixaban, and dabigatran in plasma from patients on treatment. RESULTS: For rivaroxaban (n = 74), the concentrations (mean and SD) of Heptest-STAT versus Coamatic and HemosIL assays were 179.3 ± 85.8 ng/mL versus 199.3 ± 105.7 ng/mL and 212.4 ± 115.9 ng/mL (P < 0.0001), and for apixaban (n = 26) 232.8 ± 10.0 ng/mL versus 178.4 ± 64.4 ng/mL (P < 0.0001) and 182.1 ± 73.1 ng/mL (P = 0.0002). For dabigatran (n = 74), the values of Heptest-STAT were 92.3 ± 65.0 ng/mL versus 124.3 ± 85.6 ng/mL (direct thrombin inhibitor assay, P < 0.0001) and 107.5 ± 59.7 ng/mL (S2238 assay, P = 0.0015), respectively. The values of the intraclass coefficient of correlation ranged from 0.64 to 0.91 (Bland-Altman analysis). CONCLUSIONS: The objective of the study was achieved by demonstrating a high correlation of the Heptest-STAT coagulation assay with chromogenic assays for factor Xa inhibiting NOACs and acceptably good correlation with thrombin inhibiting NOACs in plasma samples of patients on treatment.