The adsorption of dabigatran is as efficient as addition of idarucizumab to neutralize the drug in routine coagulation assays

Jacquemin, Marc; Toelen, Jaan; Feyen, Luc; Schoeters, Joke; Horenbeeck, Isa Van; Vanlinthout, Ingrid; Debasse, Mirjam; Vanassche, Thomas; Peerlinck, Katheliijne; Verhamme, Peter

doi:10.1111/ijlh.12807

Cited by 30 publications

(50 citation statements)

References 14 publications

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“…Although not explicitly mentioned by the authors, a similar pattern was seen in the study by Exner et al for NPP spiked with enoxaparin and treated with DOAC‐Stop. Prolongation of APTT results after applying DOAC‐Stop was previously reported as well . Differences between APTT results for danaparoid and between dRVVT results for all 3 anticoagulants were limited and statistically insignificant.…”

Section: Resultssupporting

confidence: 64%

The effect of unfractionated heparin, enoxaparin, and danaparoid on lupus anticoagulant testing: Can activated carbon eliminate false‐positive results?

Kesel

Devreese

2020

Research and Practice in Thrombosis and Haemostasis

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: Heparins and heparinoids interfere with functional clotting assays used for lupus anticoagulant (LAC) detection. However, current guidelines for LAC testing do not provide clear guidance on this matter. Objectives:We aimed to assess to effect of unfractionated heparin (UFH), enoxaparin, and danaparoid on LAC assays over broad anti-Xa activity ranges and to evaluate whether activated carbon (AC) is able to neutralize these effects.Methods: UFH (0.1-3.0 IU/mL), enoxaparin (0.2-2.9 IU/mL), and danaparoid (0.6-2.2 IU/mL) were spiked to normal pooled plasma. AC was added at multiple activity levels. Anti-Xa assays and LAC tests were performed on all samples using Stago analyzers and reagents.Results: Abnormal activated partial thromboplastin time (APTT) screening and mixing tests were obtained at the lowest levels for all compounds. Abnormal APTT confirmation tests were seen from 2.5 and 1.9 anti-Xa IU/mL for enoxaparin and danaparoid, respectively. Abnormal dilute Russell's viper venom test (dRVVT) screening tests were obtained from 1.6, 1.4, and 1.1 anti-Xa IU/mL for UFH, enoxaparin, and danaparoid, respectively. Mixing tests were abnormal from 2.5 and 1.3 anti-Xa IU/mL for enoxaparin and danaparoid, respectively. Abnormal dRVVT confirmation results were seen for danaparoid only from 1.9 anti-Xa IU/mL. AC was unable to neutralize anti-Xa activity in plasma and overcome the effect of the tested anticoagulants on LAC assays but may cause prolongation of APTT clotting times.Conclusions: UFH, enoxaparin, and danaparoid clearly affected LA tests; however, false-positive LAC conclusions were obtained at supratherapeutic enoxaparin and danaparoid levels only. AC may prolong APTT screen clotting times, requiring 3-step testing to avoid potential misdiagnosis of LAC. K E Y W O R D Scarbon, danaparoid, enoxaparin, heparin, lupus coagulation inhibitor

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Section: Resultssupporting

confidence: 64%

The effect of unfractionated heparin, enoxaparin, and danaparoid on lupus anticoagulant testing: Can activated carbon eliminate false‐positive results?

Kesel

Devreese

2020

Research and Practice in Thrombosis and Haemostasis

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“…adsorbs DOAC, has been investigated and found to be effective in several small laboratory studies at removing DOAC from plasma samples and allowing accurate coagulation assay testing, including LA, with the dRVVT assay (Jacquemin et al, 2015;Exner et al, 2018;Jacquemin et al, 2018;Kopatz et al, 2018;Exner et al, 2019;Platton & Hunt, 2019). In our study, APC sensitivity ratios were also significantly increased by DOAC interference (Table II), which could result in APC resistance, usually due to F5 R506Q (factor V Leiden), being missed in patients being tested on DOAC.…”

Section: Discussionmentioning

confidence: 72%

“…Several studies have investigated the use of charcoal substrate to remove DOAC from patient samples undergoing coagulation tests. DOAC Stop TM , a charcoal substrate that adsorbs DOAC, has been investigated and found to be effective in several small laboratory studies at removing DOAC from plasma samples and allowing accurate coagulation assay testing, including LA, with the dRVVT assay (Jacquemin et al , ; Exner et al , ; Jacquemin et al , ; Kopatz et al , ; Exner et al , ; Platton & Hunt, ).…”

Section: Discussionmentioning

confidence: 99%

A diagnostic solution for haemostasis laboratories for patients taking direct oral anticoagulants using DOAC‐Remove

2019

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Summary This study describes the use of a simple charcoal product (DOAC‐RemoveTM) to allow haemostasis assays on patients taking direct oral anticoagulants (DOAC). In the proposed algorithm, patients taking DOAC are screened using the dilute thrombin time (dTT) and anti‐Xa assay. If either are positive then DOAC‐Remove is utilised. In a validation, DOAC‐Remove did not interfere with coagulation testing in normal plasma or in patients on DOAC with a known lupus anticoagulant (LA). Of 1566 routine patient samples tested, 125 (8%) had evidence of anti‐Xa activity (>0·1 iu/ml) or prolonged dTT suggestive of either a direct/indirect Xa inhibitor or direct thrombin inhibitor. All of these 125 patients had a prolonged dilute Russell viper venom time (dRVVT) screening test and 106 had a LA detected by dRVVT after phospholipid correction. After DOAC‐Remove, 91 patients (73%) had a negative dRVVT screen. After further investigation only 9 (7%) had a positive LA. DOAC‐Remove prevented 5% of patients having a LA inappropriately detected. DOAC did not significantly affect the LA activated partial thromboplastin time (aPTT) ratio, protein S antigen or protein C activity. DOAC cause low intrinsic factor assays, high prothrombin time/aPTT and high activated protein C sensitivity ratio, which DOAC‐Remove reversed (P < 0·05). Despite recommendations, haemostasis testing for patients on DOAC continues; this algorithm aids diagnostic accuracy. Further validation and research are warranted.

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“…DOAC Stop has been assessed for DOAC neutralization in several studies, but mostly related to assessment of thrombophilia, 18,19,[26][27][28][29][30][31] and included in only a few studies related to factor assays. 30,32 To our knowledge, no study has previously assessed the effect of andexanet alfa on factor levels and DOAC interference. Another obvious issue to use of andexanet for in vitro reversal is cost and availability.…”

Section: Discussionmentioning

confidence: 99%

Reducing the effect of DOAC interference in laboratory testing for factor VIII and factor IX: A comparative study using DOAC Stop and andexanet alfa to neutralize rivaroxaban effects

et al. 2020

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Introduction Investigation of factors (F) VIII and IX is common, with testing important for diagnosis or exclusion of haemophilia A or B, associated acquired conditions and factor inhibitors. Rivaroxaban, a common direct anti‐Xa agent, causes significant interference in clotting assays, including substantial false reduction of factor levels. Aim To assess whether rivaroxaban‐induced interference of FVIII and FIX testing could be neutralized. Materials and methods An international, cross‐laboratory exercise for FVIII (n = 84) and FIX (n = 74), using four samples: (A) pool of normal plasma; (B) pool spiked with rivaroxaban (200 ng/mL); (C) rivaroxaban sample subsequently treated with ‘DOAC Stop’ and; (D) rivaroxaban sample treated with andexanet alfa (200 μg/mL). Testing performed blind to sample type. Results All laboratories reported normal FIX and 94% reported normal FVIII in the pool sample. Instead, 55% and 95%, respectively, reported abnormal FIX and FVIII levels for the rivaroxaban sample. DOAC Stop treatment evidenced a correction in most laboratories (100% reported normal FIX and 86% normal FVIII). Andexanet alfa provided intermediate results, with many laboratories still reporting abnormal results (59% for FVIII, 18% for FIX). We also identified reagent‐specific issues. Conclusions As expected, rivaroxaban caused false low values of FVIII and FIX. This might lead to increased testing to identify the cause of low factor levels and potentially lead to false identification of (mild) haemophilia A or B if unrecognized by clinicians/laboratories. DOAC Stop effectively neutralized the rivaroxaban effect, but andexanet alfa less so, with reagent‐related effects evident, and thus, false low values sometimes persisted.

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The adsorption of dabigatran is as efficient as addition of idarucizumab to neutralize the drug in routine coagulation assays

Cited by 30 publications

References 14 publications

The effect of unfractionated heparin, enoxaparin, and danaparoid on lupus anticoagulant testing: Can activated carbon eliminate false‐positive results?

The effect of unfractionated heparin, enoxaparin, and danaparoid on lupus anticoagulant testing: Can activated carbon eliminate false‐positive results?

A diagnostic solution for haemostasis laboratories for patients taking direct oral anticoagulants using DOAC‐Remove

Reducing the effect of DOAC interference in laboratory testing for factor VIII and factor IX: A comparative study using DOAC Stop and andexanet alfa to neutralize rivaroxaban effects

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