title: Optimisation of lupus anticoagulant tests: should test samples always be mixed with normal plasma?
abstract: 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.
authors.forename: Maarten T T
authors.initials: MT
authors.lastname: Pennings
authors.forename: Philip G
authors.initials: PG
authors.lastname: De Groot
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Albert
authors.initials: A
authors.lastname: Huisman
authors.forename: Ronald H W M
authors.initials: RH
authors.lastname: Derksen
authors.affiliation: Rolf T. Urbanus, PhD, Dept. Clinical Chemistry and Haematology, University Medical Centre Utrecht, Heidelberglaan 100, room G03.550, 3584 CX Utrecht, the Netherlands.
authors.forename: Rolf T
authors.initials: RT
authors.lastname: Urbanus
mesh_terms: D016736:Antiphospholipid Syndrome / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001779:Blood Coagulation Factors / Q000276:immunology*; D001780:Blood Coagulation Tests / Q000295:instrumentation / Q000379:methods*; D019411:Clinical Laboratory Techniques; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D016682:Lupus Coagulation Inhibitor / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D001779:Blood Coagulation Factors; D016682:Lupus Coagulation Inhibitor; D014812:Vitamin K
keywords: Lupus anticoagulant; coagulation factor deficiency; mixing test; vitamin K antagonists