Evaluation of global laboratory methods and establishing on-therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution.

BACKGROUND: Apixaban and rivaroxaban are approved for the prevention and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and embolic stroke in atrial fibrillation (AF) patients. The aim of this study was to find appropriate methods of monitoring the anticoagulant effects of are direct oral anticoagulants (DOACs) and establish on-therapy ranges using conventional tests. METHODS: A total of 184 samples were collected from 91 patients receiving DOACs. Concentrations of apixaban and rivaroxaban in plasma were accessed by an anti-factor Xa chromogenic assay. PT, APTT, antithrombin, D-dimer, dRVVT screen/confirm, FDP, and fibrinogen levels were measured. On-therapy ranges were calculated by substituting previously reported trough plasma concentrations of DOACs. RESULTS: Anti-factor Xa chromogenic assay-based DOACs levels were 26.0-279.5 (115.9 ± 56.5) ng/mL for apixaban at 2.5 mg BID, 19.9-565.1 (205.3 ± 162.4) ng/mL for apixaban at 5 mg BID, 2.3-395.3 (205.3 ± 162.4) ng/mL for rivaroxaban at 15 mg OD, 3.6-494.8 (119.6 ± 95.1) ng/mL for rivaroxaban at 20 mg OD, and 9.6-431.4 (140.8 ± 113.6) ng/mL for rivaroxaban at 15 mg BID. PT (%), antithrombin, and dRVVT confirm tests showed good correlation with plasma apixaban levels. Plasma rivaroxaban concentrations were correlated well with PT (sec), PT (%),and dRVVT confirm results. On-therapy ranges established for dRVVT confirm test by linear regression were as follows: 1.32-1.52 for apixaban 2.5 mg BID, 1.12-1.75 for apixaban 5 mg BID, 1.11-1.78 for rivaroxaban 15 mg OD, 1.09-1.64 for rivaroxaban 20 mg OD, and 1.22-1.81 for rivaroxaban 20 mg BID. CONCLUSIONS: Apixaban concentrations were well correlated with PT (%), antithrombin, and dRVVT confirm test. Rivaroxaban concentrations showed good correlation with PT (sec), PT (%), and dRVVT confirm test.

Prognostic impact of concordant and discordant bone marrow involvement and cell-of-origin in Korean patients with diffuse large B-cell lymphoma treated with R-CHOP.

AIMS: Previous studies have suggested many prognostic factors in diffuse large B-cell lymphoma (DLBCL), but the prognostic importance of cell-of-origin and discordant bone marrow involvement remains unclear. The aim of this study was to evaluate the prognostic impact of bone marrow involvement histological subtype, cell-of-origin subtype and international prognostic index (IPI) scores in patients with DLBCL. METHODS: Patients who were newly diagnosed with DLBCL and treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) were analysed. Clinical information was reviewed retrospectively. Patients were classified into negative, concordant and discordant bone marrow involvement by histological review. The cell-of-origin types were defined using immunohistochemical analysis. RESULTS: Both concordant and discordant bone marrow involvement had a negative prognostic impact on progression-free survival, independent of the standard and National Comprehensive Cancer Network (NCCN) IPI scores and cell-of-origin. Patients with non-germinal centre B-cell type showed significantly shorter progression-free survival than those with germinal centre B-cell type. However, non-germinal centre B-cell type did not have a prognostic impact on progression-free survival or overall survival after controlling for the standard and NCCN-IPI and bone marrow involvement. CONCLUSIONS: Both concordant and discordant bone marrow involvement had an adverse prognostic impact on progression-free survival and overall survival; this was independent of the standard and NCCN-IPI and cell-of-origin (non-germinal centre B-cell type). The NCCN-IPI had more powerful prognostic value than the standard IPI (sIPI). The non-germinal centre B-cell type lost significant prognostic impact on progression-free survival after adjustment for standard and NCCN-IPI and bone marrow involvement.