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

Abstract

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.

The effect of DOACs on laboratory tests and their removal by activated carbon to limit interference in functional assays

“…A particular version in mini‐tablet form was developed for more convenient application to 1ml volumes of test plasmas (DOAC Stop™, Haematex). Several studies have now been published which confirm that it and similar products (DOAC Remove) may be useful in blood coagulation testing labs to eliminate the in vitro effect of DOACs 6‐16 ; especially in testing for lupus anticoagulant.…”

Guidelines on the laboratory aspects of assays used in haemostasis and thrombosis

“…If indicated, the presence of a normal thrombin time (TT) effectively excludes the presence of a thrombin inhibitor or significant contamination with unfractionated (but not low molecular weight) heparin. Commercial products such as DOAC‐Stop (Haematex, Hornsby, NSW, Australia), 15–17 DOAC‐Remove (5‐Diagnostics, Basel, Switzerland), 18 20 mg/ml of activated charcoal 19 or Adexanet alfa 20 have been shown to remove the effect of DOAC. However, if used, results should be interpreted with caution as there may be differing limits to the concentration of the DOAC they can remove 15,17 …”

Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012; 157: 47–58): use of direct acting oral anticoagulants

“…No alternatives exist for LA detection in samples containing direct thrombin inhibitors. Some studies have suggested that absorption methods to remove the DOACs are effective (Exner et al ., ; Cox‐Morton et al ., ; Platton & Hunt, ; Zabczyk et al ., ) but none of these methods are validated in a large number of samples from true positive and negative patients with APS.…”