Functional lupus anticoagulant testing in a large retrospective cohort of thrombosis patients with direct oral anticoagulants

Abstract

functional tests for lupus anticoagulants (LA) as part of a thrombophilia workup are commonly performed in patients under anticoagulant therapy that may interfere with assay results. there is no consensus on how these tests should be assessed in patients on direct oral anticoagulants (DoAcs). in this retrospective cohort study, we analysed data from patients with a history of thrombosis in whom dilute Russell viper venom time (dRVVt), LA-sensitive aptt, and solid phase assays for antiphospholipid antibodies (aPL) were performed (n = 3,147, thereof 588 on rivaroxaban, 144 on apixaban, 1,179 on other anticoagulant drugs). The dRVVT ratio was correlated with rivaroxaban (r = 0.30, P < 10-4) but not with apixaban plasma levels. The LA-sensitive aPTT/aPTT ratio showed no correlation with DoAc levels. correspondingly, the rate of patients with abnormal dRVVt test was significantly higher (P < 10-4) under rivaroxaban (88%) than in thrombosis patients without anticoagulant medication (6%), independent from their aPL plasma levels. No isolated positive results of functional LA testing in patients on anticoagulants could be confirmed in repeated testing after discontinuation of the medication (n = 40). These data indicate that rivaroxaban should be discontinued before functional LA testing is performed. However, viable interpretation of these tests appears to be less affected in patients on apixaban.

A Diagnostic Solution for Lupus Anticoagulant Testing in Patients Taking Direct Oral FXa Inhibitors Using DOAC Filter

“…Hence, accurate aPL testing is mandatory to avoid inappropriate use of these anticoagulant compounds in this population (4,5). While detection of solid-phase antibodies aCL and aβ 2 -GPI is not affected by FXa inhibitor compounds present in tested samples (13,14), it is well-established that rivaroxaban and apixaban have the potential to compromise LA testing leading to unreliable results (false-positive/negative results) even at very low concentrations (15)(16)(17)(18)(19)(20)(21)(22). Due to their heterogeneity, LA testing should be performed using, at least, two coagulation assays of differing analytical principles, the first based on dilute Russell Viper Venom Time (dRVVT) and the second derived from activated partial thromboplastin time (aPTT) (6,18,23).…”

Testing for Lupus Anticoagulants

“…[127][128][129] To reduce likelihood of interference, samples for LA testing should be taken at a distance from LMWH administration (at least 12 hours). 126 A TT can help identify suspected undisclosed UFH, but it is less affected by LMWHs and may be normal. Local studies of anticoagulant effects on reagents in local use may be useful in guiding interpretation strategies.…”

“…Generally, dRVVT and dPT are more sensitive to DFXaIs than aPTTs. 126,130 Rivaroxaban commonly elevates dRVVT screen more than confirm, leading to false-positive interpretations, although some reagents exhibit similarly elevated screen and confirm results in normal plasma with DFXaIs and interpretation is unaffected. 126,128,[130][131][132][133] The false positivity has been observed even at trough rivaroxaban levels.…”

“…126,130 Rivaroxaban commonly elevates dRVVT screen more than confirm, leading to false-positive interpretations, although some reagents exhibit similarly elevated screen and confirm results in normal plasma with DFXaIs and interpretation is unaffected. 126,128,[130][131][132][133] The false positivity has been observed even at trough rivaroxaban levels. 134,135 Apixaban has a far less pronounced effect than rivaroxaban, 134,136,137 and the effects of edoxaban are intermediate between the two, 137 which can vary between reagents.…”

Pulmonary embolus associated with a rare provoking factor: recreational nitrous oxide use

“…The only finding of note was his lupus anticoagulant was weakly positive via dilute APTT only. This test result was likely due to the patient being on a factor Xa inhibitor which can cause false positives 9 10…”