Dilute Russell's viper venom time reagents in lupus anticoagulant testing: a well‐considered choice

Depreter, Barbara; Devreese, Katrien M.J.

doi:10.1515/cclm-2016-0245

Cited by 34Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsClinical Laboratory Practices and Quality Control

Dilute Russell's viper venom time reagents in lupus anticoagulant testing: a well‐considered choice

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Depreter, Barbara, Devreese, Katrien M.J.·2017·Clinical Chemistry and Laboratory Medicine (CCLM)

DOI 10.1515/cclm-2016-0245

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Abstract

BACKGROUND: Lupus anticoagulant (LAC) detection represents diagnostic challenges among which the multitude of available reagents and interference by anticoagulant treatment. One of the two advised tests is the dilute Russell's viper venom time (dRVVT). However, it is currently not clear whether all dRVVT reagents may be considered equivalent. The objective of the study was to evaluate the diagnostic performance of two dRVVT reagents, with special attention to the influence of anticoagulant therapy. METHODS: STA®-Staclot® dRVV Screen/Confirm (Stago, Asnières-sur-Seine, France) and dRVT-LS/dRVTL-LR (Haematex, Hornsby, Australia) were evaluated on 443 patient samples [358 consecutive patients with LAC request including six antiphospholipid syndrome (APS) patients, 18 non-consecutively selected APS patients and 37 vitamin K antagonists (VKA)-treated and 30 direct oral anticoagulants (DOAC)-treated non-APS patients]. Additionally, pooled normal plasma (PNP) was spiked with factor deficient plasma (n=33) and DOAC calibrators (n=21) to evaluate sensitivity for factor deficiencies and false-positivity rates, respectively. RESULTS: A higher number of samples were defined as LAC positive by Stago vs. Haematex [11.5% (41/358) vs. 3.63% (13/358)]. Most discordances were in the VKA and DOAC group. Haematex was less prone to VKA-related factor deficiencies, explaining the absence of false-positive LAC results in VKA-treated non-APS patients compared to 10.8% with Stago. We observed no false-positive LAC ratios with Haematex in DOAC-spiked PNP and a lower number in DOAC-treated non-APS patients. However, increased specificity seemed to be at cost of a reduced sensitivity as Haematex showed less positive APS patient samples (45.8% vs. 87.5%). CONCLUSIONS: dRVVT reagents differ in LAC sensitivity and for VKA and DOAC interference.

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Information from the confirmatory test can aid interpretation even when the mixing step is negative.
“However, information on the confirmatory test, even if the mixing step is negative, can help in the interpretation.34,35,58”
From Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis (2020) · cites this paper as [34]
Vitamin K antagonists may cause false-positive or false-negative LA results.
“Vitamin K antagonists (VKAs) may cause false-positive or false-negative results.34,35”
From Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis (2020) · cites this paper as [34]
The associations between antithrombotic treatment or thrombotic events and a negative LA test are consistent with the fact that LA testing is perturbed by anticoagulant treatment.
“The associations between antithrombotic treatment or thrombotic events and a negative LA test are consistent with the fact that LA testing is perturbed by anticoagulant treatment.23,24”
From Lupus anticoagulant test persistence over time and its associations with future thrombotic events (2022) · cites this paper as [24]

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)
MIYAKIS, S., LOCKSHIN, M. D., ATSUMI, T., BRANCH, D. W., BREY, R. L., CERVERA, R., DERKSEN, R. H. W. M., DE GROOT, P. G., KOIKE, T., MERONI, P. L., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01753.x · Cited by 7,203 · see citing works
Update of the guidelines for lupus anticoagulant detection
PENGO, V., TRIPODI, A., REBER, G., RAND, J. H., ORTEL, T. L., GALLI, M., & DE GROOT, P. G. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03555.x · Cited by 1,197 · see citing works
Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH.
Brandt, J. T., Triplett, D. A., Alving, B. M., & Scharrer, I. (1995) · PubMed · Cited by 1,164 · see citing works
Criteria for the Diagnosis of Lupus Anticoagulants: An Update: On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH
Brandt, J. T., Triplett, D. A., Alving, B., & Scharrer, I. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649901 · Cited by 993 · see citing works
Guidelines on the investigation and management of antiphospholipid syndrome
Keeling, D., Mackie, I., Moore, G. W., Greer, I. A., Greaves, M., & British Committee for Standards in Haematology (2012) · British Journal of Haematology · doi:10.1111/j.1365-2141.2012.09037.x · Cited by 740 · see citing works
Assessment of the impact of rivaroxaban on coagulation assays: Laboratory recommendations for the monitoring of rivaroxaban and review of the literature
Douxfils, J., Mullier, F., Loosen, C., Chatelain, C., Châtelain, B., & Dogné, J. (2012) · Thrombosis Research · doi:10.1016/j.thromres.2012.09.004 · Cited by 247 · see citing works
Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban—an oral, direct and selective factor Xa inhibitor
Becker, R. C., Yang, H., Barrett, Y., et al. (2011) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-011-0591-8 · Cited by 151 · see citing works
Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants
Moore, G. (2014) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0033-1364185 · Cited by 148 · cited 1× · see citing works
“dRVVT is assumed to result in less false-positive results caused by factor deficiencies and is shown to be more specific and robust compared to aPTT or other tests [11, 12].”
Result
Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH
Barnes, G. D., Ageno, W., Ansell, J., & Kaatz, S. S. (2015) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12969 · Cited by 147 · see citing works
A Hexagonal (II) Phase Phospholipid Neutralization Assay for Lupus Anticoagulant Identification
Triplett, D. A., Barna, L. K., & Unger, G. A. (1993) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649671 · Cited by 132 · see citing works
Recent guidelines and recommendations for laboratory assessment of the direct oral anticoagulants (DOACs): is there consensus?
Lippi, G., & Favaloro, E. J. (2014) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2014-0767 · Cited by 113 · see citing works
Antiphospholipid antibody testing and standardization
Devreese, K. M. J. (2014) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12234 · Cited by 98 · see citing works
Self-citation
Frequent False‐positive results of lupus anticoagulant tests in plasmas of patients receiving the new oral anticoagulants and enoxaparin
Martinuzzo, M. E., Barrera, L. H., D 'Adamo, M. A., Otaso, J. C., Gimenez, M. I., & Oyhamburu, J. (2014) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12138 · Cited by 91 · see citing works
Detection of lupus anticoagulant in the presence of rivaroxaban using Taipan snake venom time
OS, G. M. A. V., de Laat, B., Kamphuisen, P. W., Meijers, J. C. M., & de Groot, P. G. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04395.x · Cited by 87 · see citing works
Challenges in the Diagnosis of the Antiphospholipid Syndrome
Devreese, K. M. J., & Hoylaerts, M. (2010) · Clinical Chemistry · doi:10.1373/clinchem.2009.133678 · Cited by 82 · see citing works
Self-citation
Influence of dabigatran and rivaroxaban on routine coagulation assays
Bailleul, E., Châtelain, B., Demulder, A., Devreese, K. M. J., Douxfils, J., Jochmans, K., Mullier, F., Wijns, W., Soumali, M. R., Coucke, W., et al. (2014) · Thrombosis and Haemostasis · doi:10.1160/th14-02-0161 · Cited by 80 · see citing works
Self-citation
Guidelines on testing for the lupus anticoagulant. Lupus Anticoagulant Working Party on behalf of the BCSH Haemostasis and Thrombosis Task Force.
Machin, S., Giddings, J. C., Greaves, M., Hutton, R. A., Mackie, J. D., Malía, R. G., Taberner, D. A., Davidson, J. F., Barrowcliffe, T. W., Kernoff, B., et al. (1991) · Journal of Clinical Pathology · doi:10.1136/jcp.44.11.885 · Cited by 80 · see citing works
Laboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome
Devreese, K., & Hoylaerts, M. F. (2009) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2009.01243.x · Cited by 78 · see citing works
Self-citation
The Sensitivity and Specificity of Commercial Reagents for the Detection of Lupus Anticoagulant Show Marked Differences in Performance between Photo-optical and Mechanical Coagulometers
Mackie, I. J., Purdy, G., Machin, S. J., & Lawrie, A. S. (1999) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614567 · Cited by 75 · see citing works
Rivaroxaban and false positive lupus anticoagulant testing
Kaplan, Z., Butler, J., Malan, E., Gan, E., Tran, H., & Merriman, E. (2010) · Thrombosis and Haemostasis · doi:10.1160/th10-08-0511 · Cited by 71 · see citing works
Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests
Halbmayer, W., Weigel, G., Quehenberger, P., et al. (2012) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2011-0888 · Cited by 63 · see citing works
Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic antiphospholipid syndrome
Arachchillage, D. J., Mackie, I. J., Efthymiou, M., Isenberg, D. A., Machin, S. J., & Cohen, H. (2015) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12917 · Cited by 60 · see citing works
Laboratory investigation of lupus anticoagulants: mixing studies are sometimes required
FAVALORO, E. J., BONAR, R., ZEBELJAN, D., KERSHAW, G., & MARSDEN, K. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.04090.x · Cited by 48 · see citing works
Phospholipid composition controls thromboplastin sensitivity to individual clotting factors
Smith, S. A., Comp, P., & Morrissey, J. H. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01848.x · Cited by 46 · see citing works
No more mixing tests required for integrated assay systems in the laboratory diagnosis of lupus anticoagulants?
DEVREESE, K. M. J. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.03807.x · Cited by 42 · see citing works
Self-citation
Mixing test specific cut‐off is more sensitive at detecting lupus anticoagulants than index of circulating anticoagulant
Moore, G. W., Culhane, A. P., Daw, C. R., Noronha, C. P., & Kumano, O. (2016) · Thrombosis Research · doi:10.1016/j.thromres.2016.01.019 · Cited by 42 · see citing works
Commonalities and contrasts in recent guidelines for lupus anticoagulant detection
Moore, G. W. (2014) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12227 · Cited by 41 · see citing works
Assays for Detection of Antiphospholipid Antibodies
Triplett, D. A. (1994) · Lupus · doi:10.1177/096120339400300415 · Cited by 37 · see citing works
Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome
Isert, M., Miesbach, W., Schüttfort, G., Weil, Y., Tirneci, V., Kasper, A., Weber, A., Lindhoff‐Last, E., Herrmann, E. M., & Linnemann, B. (2015) · Annals of Hematology · doi:10.1007/s00277-015-2374-3 · Cited by 35 · see citing works
Differences in lupus anticoagulant final conclusion through clotting time or Rosner index for mixing test interpretation
Depreter, B., & Devreese, K. M. J. (2016) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2015-0978 · Cited by 34 · see citing works
Self-citation
Comparison of six dilute Russell viper venom time lupus anticoagulant screen/confirm assay kits
Fritsma, G., & McGlasson, D. (2013) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0033-1334865 · Cited by 33 · see citing works
Testing for new oral anticoagulants with LA-resistant Russells viper venom reagents. An in vitro study
Ellwood, L., Rubie, J., Barancewicz, A., & Exner, T. (2013) · Thrombosis and Haemostasis · doi:10.1160/th12-11-0842 · Cited by 30 · see citing works
False-positive lupus anticoagulant in patients receiving rivaroxaban
Góralczyk, T., Iwaniec, T., Wypasek, E., & Undas, A. (2014) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0000000000000235 · Cited by 29 · see citing works
The introduction of anti-phosphatidylserine/prothrombin autoantibodies in the laboratory diagnostic process of anti-phospholipid antibody syndrome: 6 months of observation
Fabris, M., Giacomello, R., Poz, A., Pantarotto, L., Tanzi, N., Curcio, F., & Tonutti, E. (2014) · Autoimmunity Highlights · doi:10.1007/s13317-014-0061-3 · Cited by 29 · see citing works
Laboratory diagnostic outcome applying detection criteria recommended by the Scientific and Standardization Committee of the ISTH on Lupus Anticoagulant
Biguzzi, E., Asti, D., Palmucci, C., Tripodi, A., & Chantarangkul, V. (2013) · Thrombosis and Haemostasis · doi:10.1160/th12-11-0850 · Cited by 21 · see citing works
Lupus anticoagulant testing and anticoagulation do not mix: quantitation of discrepant results and potential approaches to reduce false positives
Chandler, J. B., Torres, R., Rinder, H. M., & Tormey, C. A. (2014) · British Journal of Haematology · doi:10.1111/bjh.13030 · Cited by 20 · see citing works
Investigation of sensitivity for coagulation factor deficiency in APTT and PT: how to perform it?
Dumoulin, E. N., Fiers, L., & Devreese, K. M. J. (2015) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2015-0670 · Cited by 16 · see citing works
Self-citation
Lupus anticoagulants: pathogenesis and laboratory diagnosis.
Court, E. L. (1997) · PubMed · Cited by 12 · see citing works
FRI0593 Effects of New (Direct) Oral Anticoagulants on Lupus Anticoagulant Assays
Antović, J. P., Antovič, A., Norberg, E.-M., et al. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2015-eular.5847 · Cited by 1 · see citing works

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Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis
Devreese, K. M. J., de Groot, P. G., de Laat, B., Erkan, D., Favaloro, E. J., Mackie, I., Martinuzzo, M., Ortel, T. L., Pengo, V., Rand, J. H., et al. (2020) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15047 · Cited by 439 · see citing works
Self-citation
Lupus anticoagulant detection in anticoagulated patients. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis
Tripodi, A., Cohen, H., & Devreese, K. M. J. (2020) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14846 · Cited by 143 · see citing works
Self-citation
An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies
Devreese, K. M. J., Bertolaccini, M. L., Branch, D. W., de Laat, B., Erkan, D., Favaloro, E. J., Pengo, V., Ortel, T. L., Wahl, D., & Cohen, H. (2025) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2024.10.022 · Cited by 92 · see citing works
Self-citation
International Multicenter, Multiplatform Study to Validate Taipan Snake Venom Time as a Lupus Anticoagulant Screening Test with Ecarin Time as the Confirmatory Test: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies
Moore, G. W., Jones, P. O., Platton, S., Hussain, N., White, D., Thomas, W., Rigano, J., Pouplard, C., Gray, E., & Devreese, K. M. J. (2021) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15438 · Cited by 47 · see citing works
Self-citation
Current Controversies in Lupus Anticoagulant Detection
Moore, G. (2016) · Antibodies · doi:10.3390/antib5040022 · Cited by 36 · see citing works
Lupus anticoagulant test persistence over time and its associations with future thrombotic events
Colling, M. E., Ay, C., Kraemmer, D., Koder, S., Quehenberger, P., Pabinger, I., Posch, F., & Gebhart, J. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021006011 · Cited by 5 · see citing works
“This corresponded to 10-year prospective ATE, VTE, and overall thrombosis incidences of 14% (95%CI: 9-21), 20% (13-28), and 34% (26-43), respectively, and a 10-year mortality of 14% (9-22) (supplemental Figure 2).”
Background
Analytical dilemmas in lupus anticoagulant detection
Moore, G. W. (2023) · Exploration of Immunology · doi:10.37349/ei.2023.00104 · Cited by 5 · see citing works
Lupus Anticoagulant Testing in Challenging Situations: Navigating Complexities
Devreese, K. M. J. (2026) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.14490 · Cited by 2 · see citing works
Self-citation

Antiphospholipid and Thrombosis Syndromes
Bick, R. L., & Baker, W. (1994) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-2007-1001885 · Cited by 57 · see citing works
Thrombotic Risk in the Antiphospholipid Syndrome
Lim, W. (2014) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0034-1390003 · Cited by 36 · see citing works
Recurrent antiphospholipid-related deep vein thrombosis as presenting manifestation of systemic lupus erythematosus
Gattorno, M., Molinari, A. C., Buoncompagni, A., et al. (2000) · European Journal of Pediatrics · doi:10.1007/s004310050052 · Cited by 9 · see citing works
Antiphospholipide antibody profile of a patient suffering from vascular thrombosis associated with antiphospholipide syndrome-value of anticardiolipin antibodies and lupus anticoagulant in diagnostic
Glasnović, M., Bošnjak, I., Včev, A., et al. (2009)
Phlegmasia cerulea dolens as a complication of deep vein thrombosis in a man with primary antiphospholipid syndrome
Padjas, A., Brzezińska-Kolarz, B., Undas, A., et al. (2005) · Blood Coagulation & Fibrinolysis · doi:10.1097/01.mbc.0000191910.24780.81 · Cited by 10 · see citing works

Authors: Depreter, B., & Devreese, K. M. J.
Affiliations: Ghent University Hospital (BE)
Corresponding author: Devreese, Katrien M.J.
ORCID: Depreter, Barbara
Devreese, Katrien M.J.
Venue: Clinical Chemistry and Laboratory Medicine (CCLM)
Publisher: Walter de Gruyter GmbH
Published: 2016-06-22
Volume: 55
Issue: 1
Pages: 91-101
ISSN: 1434-6621 (ISSN-L)
1437-4331
DOI: 10.1515/cclm-2016-0245
OpenAlex: W2467570418
Cited by: 34
References: 39
Citations by year: 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 1
FWCI: 3.55
Type: journal article
Language: en
Open access: green
biblio.ugent.be
Licence: other-oa
Locations: Clinical Chemistry and Laboratory Medicine (CCLM) (publishedVersion)
PubMed (publishedVersion)
Ghent University Academic Bibliography (Ghent University) (publishedVersion, other-oa)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Topics: Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords: lupus anticoagulant, dilute Russell's viper venom time, antiphospholipid syndrome, vitamin K antagonists, direct oral anticoagulants, false positives, sensitivity and specificity
MeSH terms: Blood Coagulation Tests, Humans, Indicators and Reagents, Prothrombin Time, Lupus Coagulation Inhibitor

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Dilute Russell's viper venom time reagents in lupus anticoagulant testing: a well‐considered choice

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