Unveiling the complex effects of direct oral anticoagulants on dilute Russell's viper venom time assays

In 2018, the International Council for Standardization in Hematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alpha. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author’s personal experience/expert opinion and (3) good laboratory practice.

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“…51 Lastly, new products are currently under evaluation that demonstrates low to no DOAC interference for LA detection. 53,54…”

Section: Interference Of Doac On Coagulation Assaysmentioning

confidence: 99%

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

Adcock²,

et al. 2021

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“…Moreover, we in- Among the LAC assays we investigated, the presence of DOACs had the most pronounced effects on the aPTT-SP and dRVVT ratio, the former being more sensitive to dabigatran 33 and the latter to rivaroxaban, which has been shown to be dependent on the composition and concentration phospholipids present, particularly in the screen reagent. [49][50][51] Indeed, the effect of DOACs are highly impacted by the reagents used. 51 As we have used two aPTT-based reagents and one dRVVT reagent, our results may not generalize to reagents from different manufacturers.…”

Section: Discussionmentioning

confidence: 99%

“…[49][50][51] Indeed, the effect of DOACs are highly impacted by the reagents used. 51 As we have used two aPTT-based reagents and one dRVVT reagent, our results may not generalize to reagents from different manufacturers. Among patients receiving apixaban or rivaroxaban, 13 samples remained elevated when tested with the aPTT-SP after treatment with DOAC-Stop (see Figure 5A).…”

Section: Discussionmentioning

confidence: 99%

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

Baker

Jin

Pfaffroth

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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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.

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“…166 The bypassing of FX by direct activation of FII has led to studies showing that TSVT/ET testing can detect LA in the presence of the direct FXa inhibitor (DFXaI) rivaroxaban, [167][168][169] which is potentially clinically valuable because most other reagents used for LA detection are, to varying degrees, affected by DFXaIs. [170][171][172] A recent multi-centre study has validated TSVT/ET testing in non-anticoagulated patients and those anticoagulated with VKAs and all DFXaIs. 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.…”

Section: Lupus Anticoagulantsmentioning

confidence: 99%

Snake Venoms in Diagnostic Hemostasis and Thrombosis

Moore

2021

Semin Thromb Hemost

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Snake venoms have evolved primarily to immobilize and kill prey, and consequently, they contain some of the most potent natural toxins. Part of that armory is a range of hemotoxic components that affect every area of hemostasis, which we have harnessed to great effect in the study and diagnosis of hemostatic disorders. The most widely used are those that affect coagulation, such as thrombin-like enzymes unaffected by heparin and direct thrombin inhibitors, which can help confirm or dispute their presence in plasma. The liquid gold of coagulation activators is Russell's viper venom, since it contains activators of factor X and factor V. It is used in a range of clotting-based assays, such as assessment of factor X and factor V deficiencies, protein C and protein S deficiencies, activated protein C resistance, and probably the most important test for lupus anticoagulants, the dilute Russell's viper venom time. Activators of prothrombin, such as oscutarin C from Coastal Taipan venom and ecarin from saw-scaled viper venom, are employed in prothrombin activity assays and lupus anticoagulant detection, and ecarin has a valuable role in quantitative assays of direct thrombin inhibitors. Snake venoms affecting primary hemostasis include botrocetin from the jararaca, which can be used to assay von Willebrand factor activity, and convulxin from the cascavel, which can be used to detect deficiency of the platelet collagen receptor, glycoprotein VI. This article takes the reader to every area of the diagnostic hemostasis laboratory to appreciate the myriad applications of snake venoms available in diagnostic practice.

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Unveiling the complex effects of direct oral anticoagulants on dilute Russell's viper venom time assays

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 18 publications

References 42 publications

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

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

Snake Venoms in Diagnostic Hemostasis and Thrombosis

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