Effects of the oral, direct factor Xa inhibitor edoxaban on routine coagulation assays, lupus anticoagulant and anti-Xa assays

Figures & data

Figure 1. Effect of edoxaban on the APTT. The obtained APTTs using five different reagents were plotted against the edoxaban concentration in plasma. TriniCLOT aPTT HS (▴), Actin FSL (●), PTT-Automate (●), APTT-SP (■) and DG-APTT (▼). Results are shown as seconds (mean ± SD) of 10 different healthy donors.

Table 1. Mean APTT (seconds) at different concentrations of edoxaban, increase in the APTT per 100 µg/L and concentrations required to double the APTT (CT₂).

Type of APTT	Baseline (0 µg/L) Mean ± SD (range)	‘Trough’ (36 µg/L) Mean ± SD (range)	‘Peak’ (292 µg/L) Mean ± SD (range)	Mean increase APTT/100 µg/L (s)	CT2 (µg/L) Edoxaban Mean ± SD
Actin FSL	25.1 ± 1.9 (22.5–26.4)	28.6 ± 2.4 (23.5–31.7)	36.3 ± 3.1 (31.8–45.4)	3.3	743 ± 104
PTT Automate	29.6 ± 2.1 (26.5–34.2)	32.0 ± 2.5 (28.9–37.7)	44.0 ± 4.5 (39.9–53.6)	4.2	696 ± 69
DG-APTT	27.3 ± 3.4 (21.9–32.9)	30.9 ± 4.0 (25.6–38.8)	45.8 ± 7.5 (34.8–53.5)	4.7	539 ± 72
TriniCLOT	28.9 ± 2.4 (26.1–34.2)	31.1 ± 2.5 (27.8–35.9)	42.1 ± 4.0 (36.5–49.1)	3.8	758 ± 69
APTT-SP	29.2 ± 2.5 (26.9–35.0)	32.1 ± 4.0 (29.3–42.7)	44.6 ± 4.7 (39.2–53.7)	4.2	670 ± 62

Figure 2. Effect of edoxaban on the PT assay expressed as INR. Analysis of five Quick PT assays based on plain thromboplastin reagents: STA-Neoplastine (■), RecombiPlastTin 2G (▼), Technoplastin HIS (▴), Thromborel S (■), Dade Innovin (♦), and two Owren type PT assays, based on combined rabbit thromboplastin reagents: SPA+ (●), Owren’s PT (●). Results are shown as INR (mean ± SD) of 10 different healthy donors.

Table 2. Mean INR at different concentrations of edoxaban, mean INR increase per 100 µg/L and concentrations required to double the prothrombin time (CT₂).

PT-assay	‘Trough’ (36 µg/L) INR Mean ± SD	‘Peak’ (292 µg/L) INR Mean ± SD	Mean increase of INR/100 µg/L	CT2 (µg/L) Edoxaban Mean ± SD
Quick type PT
Neoplastin	0.98 ± 0.05	1.73 ± 0.15	0.27	387 ± 15
Recombiplastin	0.98 ± 0.04	1.37 ± 0.08	0.14	569 ± 36
Technoplastin	1.06 ± 0.08	1.97 ± 0.16	0.30	329 ± 22
Thromborel S	0.96 ± 0.04	1.37 ± 0.16	0.15	622 ± 55
Innovin	0.94 ± 0.04	1.22 ± 0.05	0.09	717 ± 50
Owren type PT
SPA+	1.00 ± 0.05	1.09 ± 0.06	0.03	2505 ± 239
Owren’s PT	0.99 ± 0.06	1.14 ± 0.07	0.06	1601 ± 119

Figure 3. Effect of edoxaban on antithrombin assays. One assay, Berichrom Antithrombin III, is based on thrombin (●) and the other assay, Innovance Antithrombin, is based on factor Xa (O). Results are shown as the activity (kIU/L; mean ± SD) of 10 different healthy donors.

Figure 4. Effects of edoxaban on the lupus anticoagulant test. Two integrated dRVVT assays were evaluated: Technoclone LA (O) STA dRVVT (●). The assays consist of a screenclotting test (low phospholipid) and a confirm clotting test (phospholipid rich). The results are shown as the ratio (mean ± SD) of the screen/confirm test of 10 different donors and the horizontal line indicates the ratio of 1.2 that is the cut-off for suspicion of a positive result.

Figure 5. Determination of the edoxaban plasma concentration measured by anti-Xa assays. Two assays, STA-Liquid anti-Xa using STA-Edoxaban calibrator on the STA-R MAX analyser (●), and Coamatic Heparin, calibrated with a locally produced edoxaban calibrator set and performed on the ACLTop (O). The results are shown as the anti-Xa activity (mean ± SD) of 10 different healthy donors. The solid lines are regression lines for the two assays and the equations and the r²-values of the lines are indicated in the plot.