DOAC‐Stop in lupus anticoagulant testing: Direct oral anticoagulant interference removed in most samples

Abstract

Background The use of direct oral anticoagulants (DOACs) is a convenient therapeutic option for patients at risk of thrombosis. DOACs interfere with clot‐based testing for the identification of lupus anticoagulant antibodies (LACs) in patients with antiphospholipid syndrome (APS), a common cause of acquired thrombotic disease. Objectives To evaluate a commercially available reagent DOAC‐Stop for the removal of DOAC interference encountered in LAC testing. Patients/Methods We collected a cohort of 73 test samples from patients on DOAC therapy identified at a large institutional coagulation laboratory from March to December 2019, along with samples from 40 LAC positive and negative control patients not on therapy. Samples were treated with DOAC‐Stop and tested for anti‐Xa activity and thrombin time for the removal of apixaban, rivaroxaban, argatroban, and dabigatran activity from patient samples. Treated and untreated samples were tested using the activated partial thromboplastin time, silica clotting time, and dilute Russell’s viper venom time to evaluate the reliability and utility of DOAC‐Stop. Results DOAC‐Stop markedly reduced DOAC interference from test samples (P < .05). DOAC‐Stop had no effect on LAC testing in the absence of DOAC therapy, permitting the identification of all LAC positive and negative controls. DOAC‐Stop removed false positives and false negatives resulting from DOAC interference and allows the identification of patients meeting criteria for the diagnosis of APS by LAC testing, as well as the detection of patients on rivaroxaban who are triple positive for APS. Conclusions DOAC‐Stop is an effective adjunct for the clinical laboratory faced with DOAC interference in LAC testing.

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

“…It is noteworthy that the residual DOAC levels measured here were below the highest concentration not causing false‐positive LAC results (even for the LAC screening steps) in spiked plasma, except for dabigatran (27 ng/mL). Residual DOAC levels after the use of DOAC‐removing agents are reported in several studies, some with even higher leftover concentrations 24‐26,28‐30,44 . With this observation and following the recommendation of the ISTH guidelines, 14,15 a residual DOAC concentration measurement should be performed after DF treatment to ensure complete DOAC removal, before interpretation of the obtained LAC results.…”

Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants

“…As a historical link to LA guidelines, readers may be interested to know that Exner was lead author of the 1991 ISTH LA guidelines, 21 as well as authoring dozens of other papers on LA. The product and its use have now been reported in several studies 26‐43 (Table 3; Table ). The product represents a form of activated charcoal, and one pellet of the commercial product can remove a therapeutic level of all the DOACs (dabigatran, rivaroxaban, and apixaban being those most well studied) from 1 ml of citrate anticoagulated plasma.…”

Snake Venoms in Diagnostic Hemostasis and Thrombosis

“…173 Although adsorbents for direct oral anticoagulant (DOAC) removal from plasma are available, they have their own limitations, and cannot mitigate for the effects of VKA anticoagulation. 158,174,175 Of potential clinical import is that T/E ratio and TSVT/ET testing have been reported to detect small numbers of LA unreactive in dRVVT and aPTT. 162,164,176,177…”

“…173 Although adsorbents for direct oral anticoagulant (DOAC) removal from plasma are available, they have their own limitations, and cannot mitigate for the effects of VKA anticoagulation. 158 174 175…”