Thromb Haemost 2014; 112(04): 736-742
DOI: 10.1160/TH14-02-0122
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Optimisation of lupus anticoagulant tests: should test samples always be mixed with normal plasma?

Maarten T. T. Pennings
1   Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands
,
Philip G. de Groot
1   Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands
,
Joost C. M. Meijers
2   Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
3   Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands
,
Albert Huisman
1   Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands
,
Ronald H. W. M. Derksen
4   Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
,
Rolf T. Urbanus
3   Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands
› Author Affiliations
Financial support: MTT Pennings is funded by the Dutch Arthritis Foundation (Grant number 10–1–307) and RT Urbanus is funded by the Dutch Heart Foundation (2010T068).
Further Information

Publication History

Received: 11 February 2014

Accepted after major revision: 08 May 2014

Publication Date:
20 November 2017 (online)

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Summary

Coagulation factor deficiencies are thought to interfere with the detection of the phospholipid-dependent coagulation inhibitor known as lupus anticoagulant (LA). Treatment with vitamin K antagonists (VKA) in particular, is thought to preclude accurate LA assessment. For this reason, the procedure to detect LA includes a mixing test, in which coagulation factor deficiencies are corrected by mixing samples with an equal volume of normal plasma. Despite these mixing tests, interpretation of LA test results is considered difficult in patients receiving high intensity VKA treatment. As a result, VKA treatment is often temporarily discontinued to allow LA assessment. However, whether coagulation factor deficiencies influence LA test results is unclear. We found that neither deficiency of a single coagulation factor, nor a functional coagulation factor deficiency due to high intensity VKA treatment, resulted in false positive dRVVT- or APTT-based (silica clotting time; SCT) LA test results. LA was readily detected in unmixed samples from VKA-treated LA-positive patients with both dRVVT and SCT reagents. VKA treatment caused an underestimation of the strength of the LA with SCT reagents, but did not lead to misclassification of LA status. Although mixing with normal plasma during both screen and confirm tests allowed more accurate assessment of the strength of the LA with SCT reagents in samples with an international normalised >2.5, the mixing procedure itself lead to misclassification of LA in weakly positive samples from patients not treated with VKA. Based on these findings, we conclude that mixing studies are not necessary during LA-assessment.