Abstract Number: PB0652
Meeting: ISTH 2020 Congress
Background: DOAC-Stop® is a recently manufactured product which can neutralise the direct oral anticoagulants (DOAC) in plasma samples in vitro. However, there are still some grey areas regarding its use.
Aims: To investigate the effect of DOAC-Stop® on several oral and parenteral anticoagulants using standard and research-based coagulation assays.
Methods: We analysed pools of normal platelet poor plasma (PPP), warfarinised PPP (INR 2.1, 3.2, 4.2), normal PPP spiked with direct factor Xa inhibitors (apixaban 182, 265 ng/mL; edoxaban 151, 220 ng/mL; rivaroxaban 241, 339 ng/mL), direct thrombin inhibitor (dabigatran 203, 318 ng/mL), indirect factor Xa inhibitors (enoxaparin 0.93, 1.68 U/mL; fondaparinux 1.62, 2.16 µg/mL). Samples treated with DOAC-Stop® were compared with untreated samples. The following assays were performed: anti-Xa, diluted thrombin time, APTT, PT/INR, lupus anticoagulant (LA), factor assays (I, II, VII, VIII, IX, X, XI, XII), calibrated automated thrombography (CAT) with TF 5pM, thromboelastography (TEG).
Results: After DOAC-Stop® treatment, the DOACs showed undetectable anticoagulant concentrations and complete normalisation of APTT and PT/INR. The false positive LA results obtained with rivaroxaban were normalised.
Direct factor Xa inhibitors were completely normalised on the CAT, while for dabigatran only lag time and time-to-peak were normalised (Table 1). On the TEG, the MA of all DOACs was normalised, whereas a variable degree of normalisation of the other parameters was observed (Table 2).
Normal and warfarinised PPP on the CAT showed shortening of lag time and time-to-peak and prolongation of ETP and peak; on the TEG they showed an increase of R time. There showed also a trend towards a reduction of factors VIII, IX, X, XI, XII levels.
Conclusions: Our preliminary findings indicated that while basic coagulation assays were normalised by DOAC-Stop®, there might be potential for reduction of plasma levels of several coagulation factors, suggesting a certain level of DOAC-Stop® binding which could affect other assays.
| Lag time (ref. 3.54-4.34 min) | ETP (ref. 1852.7-2225.4 nM*min) | Peak (ref. 243.45-349.02 nM) | Time to peak (ref. 6.86-8.53 min) | |||||
| Sample | Before | After | Before | After | Before | After | Before | After |
| Normal PPP | 4.17 (0.23) | 3.84 (0.23) | 1911.0 (52.3) | 2013.0 (12.7) | 270.33 (5.48) | 301.69 (4.96) | 8.00 (0) | 7.33 (0) |
| Warfarinised PPP INR 4.2 | 11.67 (0) | 10.84 (0.23) | 275.0 (12.7) | 296.5 (19.1) | 46.67 (1.62) | 51.17 (3.17) | 15.00 (0) | 14.00 (0) |
| Apixaban 265 ng/mL | 8.92 (0.47) | 3.91 (0) | 643.0 (0) | 1855.5 (23.3) | 27.57 (2.54) | 262.72 (3.20) | 14.43 (1.65) | 7.58 (0) |
| Edoxaban 220 ng/mL | 11.59 (0) | 3.74 (0.24) | 643.0 (5.7) | 1945.5 (132.2) | 31.25 (0.64) | 282.46 (11.67) | 24.78 (0.24) | 7.42 (0.23) |
| Rivaroxaban 339 ng/mL | 12.09 (0.23) | 3.91 (0) | 467.5 (20.5) | 1956.0 (123.0) | 15.66 (0.33) | 259.95 (11.79) | 28.28 (0.47) | 7.91 (0) |
| Dabigatran 318 ng/mL | 18.50 (0.71) | 3.84 (0.23) | 748.0 (2.8) | 1652.5 (23.3) | 148.06 (3.37) | 224.60 (2.05) | 20.83 (0.71) | 7.84 (0.23) |
| Enoxaparin 1.68 U/mL | Flat CAT traces | |||||||
| Fondaparinux 1.62 µg/mL | 14.00 (0) | 11.50 (0.24) | 242.5 (0.71) | 274.5 (3.54) | 12.90 (0.20) | 16.56 (0.11) | 24.84 (0.23) | 20.33 (0) |
[Table 1. CAT results before and after DOAC Stop® treatment]
| R time (ref. 9.23-15.01 min) | K time (ref. 1.56-4.12 min) | Angle (ref. 40.27-63.44 deg) | MA (ref. 28.83-36.57 mm) | |||||
| Sample | Before | After | Before | After | Before | After | Before | After |
| Normal PPP | 10.05 (0.64) | 12.55 (0.49) | 3.05 (0.21) | 3.15 (1.06) | 51.45 (2.05) | 47.30 (9.48) | 30.80 (0.42) | 32.15 (2.19) |
| Warfarinised PPP INR 4.2 | 18.15 (0.21) | 23.80 (1.41) | 6.60 (0.57) | 5.90 (0.28) | 26.80 (3.25) | 35.50 (2.69) | 32.35 (0.49) | 33.65 (0.35) |
| Apixaban 265 ng/mL | 17.70 (0.14) | 16.55 (1.91) | 8.55 (0.21) | 4.50 (1.84) | 28.25 (2.47) | 37.90 (14.42) | 23.45 (0.64) | 29.05 (1.77) |
| Edoxaban 220 ng/mL | 25.35 (3.18) | 16.50 (0.42) | 8.90 (0.14) | 3.65 (0.49) | 25.05 (3.89) | 40.15 (5.59) | 25.95 (1.63) | 30.55 (2.05) |
| Rivaroxaban 339 ng/mL | 29.80 (2.40) | 16.30 (0.14) | 13.25 (0.49) | 3.70 (0.42) | 17.40 (0.71) | 43.75 (0.21) | 23.30 (1.84) | 31.0 (1.27) |
| Dabigatran 318 ng/mL | 47.75 (1.34) | 17.80 (1.27) | 10.20 (7.35) | 4.15 (0.92) | 25.60 (15.27) | 41.05 (6.01) | 33.55 (2.62) | 35.35 (0.49) |
| Enoxaparin 1.68 U/mL | Flat TEG traces | |||||||
| Fondaparinux 1.62 µg/mL | Flat TEG traces | |||||||
[Table 2. TEG results before and after DOAC Stop® treatment]
To cite this abstract in AMA style:
Riva N, Vella K, Hickey K, Gatt P, Grima C, Zammit D, Kitchen S, Makris M, Ageno W, Gatt A. The Effect of DOAC-Stop® on Several Oral and Parenteral Anticoagulants [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-effect-of-doac-stop-on-several-oral-and-parenteral-anticoagulants/. Accessed September 29, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-effect-of-doac-stop-on-several-oral-and-parenteral-anticoagulants/