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

Farkh, Carine; Ellouze, Syrine; Gounelle, Louis; Houari, Mama Sad; Duchemin, Jérôme; Proulle, Valérie; Fontenay, Michaëla; Delavenne, Xavier; Jourdi, Georges

doi:10.3389/fmed.2021.683357

Cited by 14 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In practice, the 15‐minute one‐step DF procedure may be preferred to a 20‐minute two‐step (incubation and centrifugation) procedure of DS. However, a 22.6% volume loss after filtration with a mean recovered volume of 465 µL, in line with observations of Sevenet et al 34 and Farkh et al, 46 could be a limiting factor in clinical practice. In this regard, a full three‐step LAC testing in two systems may need the use of 2 DFs, which is economically less interesting and may lead to insufficient sample volume (2 × 600 µL PPP).…”

Section: Discussionsupporting

confidence: 85%

“…Discordances within the nonanticoagulated patient group, with final LAC results becoming negative after filtration, mostly originated from a shorting in dRVVT screen CT. Shorter postfiltration CTs of the LAC assays, however clinically nonsignificant, were also observed by Sevenet et al 34 In addition, the recently published work of Farkh et al 46 on the effect of DF on LAC testing reported no statistically significant differences for dRVVT and silica clotting time (SCT) screen or screen/confirm ratios in a control group of 68 nonanticoagulated patient samples. However, 4 of 37 dRVVT and 5 of 15 SCT (weakly) positive screen ratios changed to negative after filtration.…”

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

Linskens

Kesel

Devreese

2022

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background DOAC Filter (DF) is a new device to overcome interference in lupus anticoagulant (LAC) testing by direct oral anticoagulants (DOACs). Objectives We evaluated DOAC removal from plasma and elimination of DOAC interference in LAC testing by DF, and impact of DF on LAC assays in a representative patient cohort, including a comparison with DOAC‐Stop (DS). Methods Normal pooled plasma (NPP) was spiked with increasing concentrations of apixaban, rivaroxaban, edoxaban, and dabigatran. DOAC and LAC was measured on untreated, DF‐treated, and DS‐treated spiked samples. Coagulation parameters and thrombin generation were measured on patient samples (n = 20) before and after DF. Patients treated with DOAC, vitamin K antagonist, or heparin and nonanticoagulated patient samples (n = 139) were tested for LAC before and after DF. Results In spiked NPP, levels were below the lower limit of quantification (LLoQ) after DF/DS treatment for all DOAC concentrations. Following DF, levels were below LLoQ for 53 of 56 DOAC‐containing patient samples. Twenty‐eight of 33 LAC‐positive DOAC‐containing samples became negative after filtration, whereas 5 remained LAC‐positive (1/5 from a patient with antiphospholipid syndrome [APS]). Four LAC‐positive DOAC‐containing samples (from patients without APS), became negative after filtration, whereas they remained LAC positive after DS. In the non‐DOAC patient groups following DF, LAC changed from positive to negative in 8 (due to a procoagulant effect) and vice versa in 2 cases. Conclusion DF reduces DOAC interference in LAC testing. As incomplete DOAC removal may occur, DOAC measurements should be performed after filtration. A procoagulant effect after filtration may lead to erroneous LAC results in non–DOAC‐containing samples. Therefore, using DF should be restricted to DOAC‐containing samples.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 68%

Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

Linskens

Kesel

Devreese

2022

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…Since the beginning of the use of DOAC, their presence has been described to affect coagulation tests [11,12]. Several publications have established their influence on individual tests ranging from determination of factor levels to thrombophilia [13][14][15].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Determination of Dabigatran, Rivaroxaban, and Apixaban in Lupus Anticoagulant-Positive Patients

et al. 2021

View full text Add to dashboard Cite

Background: The effect of direct oral anticoagulants (DOAC) on laboratory tests dependent on the production of their targets, factor IIa and factor Xa, is a well-known problem and can cause both false positive and negative results. In particular, the situation in patients who develop lupus anticoagulant (LA) antibodies is highly complex. To evaluate the effectiveness of DOAC therapy in lupus-positive patients, 31 samples were enrolled in this retrospective study. All patient samples were spiked with three types of DOAC (dabigatran, DABI; rivaroxaban, RIVA; and apixaban, API) in a concentration that significantly influenced the screening test for LA and thus can mask the presence of LA. Subsequently, the DOAC was always unbound by the DOAC-Stop procedure. DOAC levels before and after binding were determined by functional assays, followed by liquid chromatography coupled with mass spectrometry (LC-MS) analysis. Methods: The determination of DOAC levels was performed by direct thrombin assay and determination of anti-Xa activity with specific calibration as functional tests for DABI and xabans (API and RIVA). To determine concentration levels of API, DABI, and RIVA, our in-house LC-MS method was used. Results: The results of LA-positive samples show significant differences between functional tests and the LC-MS method both before and after DOAC binding. Conclusions: The acute findings of the presence of LA-type antibodies fundamentally affects the determination of DOAC by functional tests, and in this case, it is necessary to use LC-MS analysis to determine the true value. If patients treated with DOAC develop LA of medium and higher titers, we do not recommend checking DOAC levels with functional tests.

show abstract

“…Another activated charcoal‐based product called DOAC‐Remove has subsequently been produced by another commercial manufacturer (5‐Diagnostics, Switzerland), and seems to have similar features to DOAC‐Stop 38 , 39 , 44 , 45 , 46 , 47 , 48 , 49 , 50 (Table 3 ; Table S2 ). A third product is available from a third manufacturer (Stago Diagnostics) and is called DOAC‐filter 51 , 52 (Table 3 ; Table S2 ). A different type of filter has recently been released for sale by 5‐Diagnostics, called DP‐filter; studies on the device appear to only have been published in abstract form.…”

Section: Anticoagulant Neutralizersmentioning

confidence: 99%

Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants

Favaloro

Pasalic

2022

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background Lupus anticoagulants (LA) are one laboratory criterion for classification of antiphospholipid syndrome, with presence of vascular thrombosis and/or pregnancy/fetal morbidity being clinical criteria. The presence of LA is detected (or excluded) by laboratory testing, with the activated partial thromboplastin time and dilute Russell's viper venom time the most commonly used tests. Given the association of thrombosis with LA, it is no surprise that anticoagulants are used to treat or manage such patients. Objectives To review and discuss interferences from anticoagulants on LA testing, and strategies to mitigate these. Methods This narrative review assessed interference from commonly used anticoagulants, focusing on LA testing while on direct oral anticoagulants (DOACs), including use of DOAC neutralizers. Results The classical anticoagulants comprise vitamin K antagonists such as warfarin, and heparins, predominantly unfractionated heparin and low molecular weight heparin (LMWH). DOACs have emerged with favorable efficacy and safety. These comprise two classes: direct anti‐thrombin (anti‐IIa; dabigatran) or direct anti‐Xa (rivaroxaban, apixaban, edoxaban) agents. All anticoagulants affect clotting assays, although there are differences in effects according to anticoagulant and assay. Nevertheless, because of such interferences, anticoagulants can lead to false‐negative or false‐positive LA findings. Several strategies can mitigate such interferences, including avoidance of testing while patients are on such anticoagulants, temporarily switching to an anticoagulant (i.e., LMWH) with less assay interference, testing for LA at nadir levels of anticoagulants, and/or use of anticoagulant neutralizers. Conclusion Whilst the best approach is to avoid LA testing on patients taking anticoagulants; if unavoidable, testing may be facilitated by various mitigating strategies.

show abstract

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

Cited by 14 publications

References 35 publications

Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

Evaluation of the Determination of Dabigatran, Rivaroxaban, and Apixaban in Lupus Anticoagulant-Positive Patients

Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants

Contact Info

Product

Resources

About