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Table 3 Effect of different DOACs in commonly used LA assays. Adapted from references [45, 46, 48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64]

From: Antiphospholipid Syndrome Committee of the Brazilian Society of Rheumatology position statement on the use of direct oral anticoagulants (DOACs) in antiphospholipid syndrome (APS)

Reference

DOAC

Tests analyzed

Results

Merriman (2010)

Rivaroxaban

aPTT (Triniclot), aPTT (STAClot), dRVVT (screen, confirm and ratio), Kaolin, DTT

False positive dRVVT ratio (88.9%) - all other tests negative / normalization of LA after discontinuation in all but one patient

van Os (2011)

Rivaroxaban

aPTT (screen PTT-LA and confirm Actin FS), dRVVT (screen LA-1 and confirm LA-2), and snake venom assays (screen TSVT and confirm ECT)

False positive dRVVT ratio (40% of SLE w/o aPL became LA positive after rivaroxaban mixing)

Halbmayer (2012)

Dabigatran

dRVVT (screen, confirm, standard ratio, and normalized ratio)

Higher frequency of false positive dRVVT ratio with increasing dabigatran concentrations

Martinuzzo (2014)

Rivaroxaban, dabigatran

aPTT, dRVVT (screen, confirm, ratio), SCT (screen, confirm, ratio)

False positive dRVVT ratio (76.5–100%)

Hillarp (2014)

Apixaban

aPTT, dRVVT (screen, confirm and ratio)

Apixaban did not cause false-positive results

Kim (2014)

Dabigatran

aPTT (PTT-LA, STAClot-LA)

False positive aPTT ratio (50% borderline and 40% positive)

Arachchillage (2015)

Rivaroxaban

Textarin time, dPT, dRVVT (3 methods: Siemens LA-1/LA-2, HemosIL dRVVT screen and confirm, and in-house dRVVT), TSVT/ECT

In vitro: false positive dRVVT ratio by conventional assays, but not in-house assay (90% normal controls and 92% LA-negative APS patients)

Ex vivo: false-positive dRVVT ratio (100%) - remained false-positive at 18 h after the last dose of rivaroxaban

Bonar (2015)

Dabigatran

dRVVT (screen, STAClot confirm and ratio)

False positive dRVVT ratio (in vivo and ex vivo)

Góralczyk (2015)

Rivaroxaban

aPTT (PTT-LA screen and STAClot confirm), dRVVT (2 methods: HemosIL screen and confirm, and LA-1/LA-2)

False positive dRVVT ratio (patients were retested and became LA negative after 24 h of rivaroxaban discontinuation)

Bonar (2016)

Rivaroxaban, apixaban

dRVVT (screen, STAClot confirm and ratio)

False positive dRVVT ratio (rivaroxaban, but not apixaban, caused increased dRVVT ratio ≥ 1.2)

Gosselin (2016)

Rivaroxaban, apixaban, and edoxaban

dRVVT (3 methods: Siemens LA-1/LA-2, CRYOCheck LA-1/LA-2, dRV-LS/dRV-LR), hexagonal phase (STAClot-LA)

False positive dRVVT ratio (for all DOACs)

Pouplard (2016)

Rivaroxaban

dRVVT (STAClot DRVVT), TSVT/ECT

False positive dRVVT ratio; TSVT/ECT was not influenced by rivaroxaban

Ratzinger (2016)

Rivaroxaban, apixaban, and dabigatran

aPTT, dRVVT

False positive dRVVT ratio:

- Dabigatran: 43.3%;

- Rivaroxaban: 30%;

- Apixaban: 20.7% (w/o dose dependent increase).

Antovic (2017)

Rivaroxaban, apixaban, and dabigatran

aPTT, dRVVT

False positive dRVVT ratio (≥1.2):

- Dabigatran: 73%;

- Rivaroxaban: 75%;

- Apixaban: 76%.

Seheult (2017)

Rivaroxaban, apixaban, and dabigatran

aPTT, dRVVT, TII + PT

False positive dRVVT ratio and TTI + PT (aPTT was less affected);

Apixaban was less affected than rivaroxaban;

After rivaroxaban discontinuation, LA positivity dropped from 83 to 26%.

Flieder (2018)

Rivaroxaban, apixaban, and dabigatran

aPTT, dRVVT (HemosIL and STAClot)

False positive dRVVT ratio:

- Dabigatran: 20% (HemosIL) and 71% (STAClot);

- Rivaroxaban: 70% (IL) and 100% (STAClot):

- Apixaban: no influence.

Less important change in aPTT in all DOACs.

Hillarp (2018)

Edoxaban

dRVVT (Technoclot and STAClot)

False positive dRVVT ratio on Technoclot, but not with STAClot

Martinuzzo (2018)

Rivaroxaban

dRVVT (HemosIL and STAClot)

False positive dRVVT ratio (89.2% with HemosIL and 86.2% with STAClot)

Platton (2018)

Rivaroxaban and apixaban

dRVVT (Siemens LA1 and LA2)

dRVVT screen and confirm were falsely increased for both rivaroxaban and apixaban groups. After treatment with DOAC Stop, both dRVVT screen and confirm decreased to normal values.

  1. aPTT activated partial thromboplastin time, DOAC direct oral anticoagulant, dRVVT dilute Russell’s viper venom time, LA lupus anticoagulant, TII + PT thromboplastin inhibition index with prothrombin time, TSVT Taipan snake venom time, ECT Ecarin clotting time