Testing for Lupus Anticoagulants

Abstract

Lupus anticoagulant (LA) is one of the three criteria antiphospholipid antibodies (aPLs) employed in classification, and by default diagnosis, of antiphospholipid syndrome (APS). Detection of LA is not via calibrated assays but is based on functional behavior of the antibodies in a medley of coagulation assays. A prolonged clotting time in a screening test is followed by demonstration of phospholipid dependence and inhibitory properties in confirmatory and mixing tests, respectively, which are modifications of the parent screening test. Complications arise because no single screening test is sensitive to every LA, and no test is specific for LA, because they are prone to interference by other causes of elevated clotting times. Several screening tests are available but the pairing of dilute Russell's viper venom time (dRVVT) with LA-sensitive activated partial thromboplastin time (aPTT) is widely used and recommended because it is proven to have good detection rates. Nonetheless, judicious use of other assays can improve diagnostic performance, such as dilute prothrombin time to find LA unreactive with dRVVT and aPTT, and the recently validated Taipan snake venom time with ecarin time confirmatory test that are unaffected by vitamin K antagonist and direct factor Xa inhibitor anticoagulation. Expert body guidelines and their updates have improved harmonization of laboratory practices, although some issues continue to attract debate, such as the place of mixing tests in the medley hierarchy, and areas of data manipulation such as assay cut-offs and ratio generation. This article reviews current practices and challenges in the laboratory detection of LA.

Autoimmune Diseases Affecting Hemostasis: A Narrative Review

“…As already briefly mentioned, antibodies can develop against various phospholipids and give rise to APS, an auto-immune condition associated both with thrombosis and pregnancy/fetal morbidity/mortality [ 12 , 13 , 14 , 15 , 57 ]. These autoantibodies can be detected in the laboratory using either ‘solid phase’ assays (by ELISA or chemiluminescence), as well as liquid phase (or clot-based) assays for the so-called lupus anticoagulant (LA) [ 58 , 59 , 60 ]. The ‘solid phase’ antiphospholipid antibody (aPL) assays include ‘anti-cardiolipin’ (aCL), ‘anti-beta-2-glycoprotein I’ (aβ2GPI), ‘anti-prothrombin’ (aPT), ‘anti-phosphatidylserine’ (aPS), or complexes (such as ‘anti-phosphatidylserine/prothrombin’ [aPS/PT] complex).…”

“…Within the diagnosis of APS, the titre (or strength) of the antibodies detected, as well as the number of different activities (e.g., double positive or triple positive) align to the thrombotic risk profile. The clot-based assay approach for LA requires the performance of various clotting assays based on different principles and using different levels (low and high) of phospholipids to increase or reduce sensitivity to LA [ 58 , 60 ]. Unfortunately, although LA tends to be more highly associated with adverse events in APS than solid phase assays, LA tests are also very sensitive to many clinical anticoagulants, which may be given to patients to treat or prevent thrombosis, but when present can lead to false positive LA findings [ 61 ].…”

Laboratory Diagnostics for Thrombosis and Hemostasis Testing—Part I

“…Close attention must be paid to the preanalytical (specimen collection and handling), 1 analytical (the testing process), 2 and postanalytical (test interpretation contribution to diagnosis and treatment) 3 variables associated with coagulation testing to assure accurate reporting of assay result(s) and corresponding result interpretation(s). The manuscripts in this edition of the journal represent state of the art summaries of testing aspects for antiphospholipid antibodies (including lupus anticoagulant [LA] 4 and solid phase testing 5 ), D-dimer, 6 activated protein C (APC) resistance, 7 and von Willebrand factor (VWF), 8 9 10 11 12 13 highlighting information essential for accurate diagnosis and monitoring of common disorders that significantly impact health care systems and patient lives.…”

“…13 The contributions to this issue begin with a thorough discussion of pertinent aspects of LA testing by Moore, with a focus on new assays that are not based on activated partial thromboplastin time or dilute Russell viper venom time, diagnostic algorithms including placement of when to perform mixing studies, approach to result interpretation, and the effects of anticoagulants on testing. 4 A highlight of this manuscript is a table, which shows results patterns in 26 examples of LA testing.…”

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“…Close attention must be paid to the preanalytical (specimen collection and handling), 1 analytical (the testing process), 2 and postanalytical (test interpretation contribution to diagnosis and treatment) 3 variables associated with coagulation testing to assure accurate reporting of assay result(s) and corresponding result interpretation(s). The manuscripts in this edition of the journal represent state of the art summaries of testing aspects for antiphospholipid antibodies (including lupus anticoagulant [LA] 4 and solid phase testing 5 ), D-dimer, 6 activated protein C (APC) resistance, 7 and von Willebrand factor (VWF), [8][9][10][11][12][13] highlighting information essential for accurate diagnosis and monitoring of common disorders that significantly impact health care systems and patient lives.…”