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Cited by 23Blood Coagulation and Thrombosis MechanismsClinical Laboratory Practices and Quality ControlAtrial Fibrillation Management and Outcomes

Unveiling the Complex Effects of Direct Oral Anticoagulants on Dilute Russell’s Viper Venom Time Assays

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Hillarp, Andreas, Strandberg, Karin, Gustafsson, Kerstin M., Lindahl, Tomas L.·2020·Journal of Thrombosis and Haemostasis
DOI 10.1111/jth.14829
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Abstract

INTRODUCTION: Dilute Russell viper venom time (dRVVT) assays can be affected by direct oral anticoagulants (DOACs), which may cause false-positive results. However, there are conflicting results indicating significant differences between different reagents and DOACs. OBJECTIVES: To evaluate the effect of DOACs on dRVVT assays. MATERIAL AND METHODS: Samples were prepared by adding DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) to pooled normal plasma in the concentration range 0 to 800 µg/L. Six integrated dRVVT reagents were used, all composed of a screen assay (low phospholipid content) and a confirm assay (high phospholipid content). The screen/confirm dRVVT results were expressed as normalized ratios. To further evaluate the observed differences between tests and DOACs, addition of synthetic phospholipids was used. RESULTS: The dRVVT ratios increased dose dependently for all DOACs, with four of the six tests and the DOAC rivaroxaban having the greatest effect. With one test, the ratios were almost unaffected with increasing DOAC concentration, whereas another test revealed a negative dose dependency for all DOACs. Variable DOAC effects can be explained by different effects on dRVVT screen and confirm clotting time. Adding synthetic phospholipids to samples containing rivaroxaban resulted in greatly reduced screen clotting times and thereby lower calculated dRVVT ratios. CONCLUSIONS: There is a great variability in the dRVVT test result with different DOACs. The dRVVT ratios are unaffected for some reagents and this can be explained by an equal dose-dependent effect on both screen and confirm assays. The phospholipid type and content of the different reagents may contribute to the observed differences.

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  • All DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives).

    “all DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives) [73,74,75,76,77,78].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [75]

    The Results and Discussion report that rivaroxaban affected screening more than confirmation in four of six assays and produced false-positive ratios in three. The Introduction notes that apixaban may cause false-negative results, but the Discussion says apixaban showed a similar, less pronounced pattern to rivaroxaban in some assays; opposite effects depended on the reagent. The paper does not establish that every DOAC prolongs both procedures in every assay. (LLM, conf=0.88)

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Authors
Hillarp, A., Strandberg, K., Gustafsson, K. M., & Lindahl, T. L.
Affiliations
  • Hallands sjukhus Halmstad (SE)
  • Region Skåne (SE)
  • Linköping University (SE)
Corresponding author
Lindahl, Tomas L.
ORCID
Venue
Journal of Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2020-08
Volume
18
Issue
8
Pages
1866-1873
ISSN
1538-7836 (ISSN-L)
DOI
10.1111/jth.14829
OpenAlex
W3015356890
Cited by
23
References
0
Citations by year
2026: 2 · 2025: 1 · 2024: 7 · 2023: 3 · 2022: 3 · 2021: 7
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thrombosis and Haemostasis (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
Keywords
direct oral anticoagulants, dilute Russell's viper venom time, coagulation tests, false positives, dabigatran, rivaroxaban, apixaban, edoxaban, synthetic phospholipids, clotting time
MeSH terms
Administration, Oral, Anticoagulants, Blood Coagulation, Blood Coagulation Tests, Humans, Partial Thromboplastin Time, Prothrombin Time, Lupus Coagulation Inhibitor

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