Lupus anticoagulants (LA) are a heterogeneous group of immunoglobulins that may develop spontaneously or as a consequence of autoimmune disease. They have the ability to bind to proteins such as prothrombin, β2 glycoprotein-1 or others in complexes with negatively changed phospholipids. LA positive tests have been associated with vascular thrombosis, pregnancy morbidity and antiphospholipid syndrome. The presence of a LA prolongs phospholipid dependent coagulation tests.
The laboratory diagnosis of LA is used for decision making, support and monitoring of patients affected. Pre analytical variables associated with collection, plasma preparation, storage and handling present potential issues with the accurate diagnosis of LA.
To date there is no reliable standard for LA testing and there is heterogeneity in testing protocols, standardisation of testing and subsequent interpretation of results.
Three key societies (BCSH[1], ISTH[2], CLSI[3]) currently have guidelines for LA testing with some variation in approach. There is general agreement on sample preparation, use of the dilute Russell viper venom time (dRVVT), use of normalised ratios, demonstration of phospholipid dependence, approach to demonstrate inhibition and reporting. The ISTH recommends employing only dRVVT and APTT which is in contrast the BCSH and CLSI. It is acknowledged that 1:1 mixing tests have the potential to give false negatives. Further there remains differing opinions on setting of cutoffs for testing, making a reliable approach to LA testing difficult.
Both the ISTH and CLSI suggest exercising caution when interpreting results on patients receiving unfractionated heparin (UFH), whilst the BCSH recommends that testing should not be done on patients whilst receiving UFH as it may lead to misleading results. CLSI does discuss the role of heparin neutralisation suggesting that this may be used to assist in diagnosis of LA whilst patients are receiving anticoagulation.
The introduction of direct oral anticoagulants (DOAC) testing of patient for LA and other haemostatic tests may be affected by these new agents. The dRVVT is highly sensitive to DOACs and testing of patients for LA whilst receiving these drugs makes interpretation and testing problematic.
Whilst all guidelines cover testing of patients receiving vitamin K antagonist treatment there is poor guidance on dealing with patients receiving UFH and DOACs.
Testing for LA is challenging and laboratory staff must have due regard for pre-analytical variables, test selection and interpretation of results in order to provide meaningful results to the clinician. The current guidelines provide approaches to standardising practice; however the complexity of testing and interpretation of results continues to provide challenges.
[1] Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol 2012;157(1):47–58
[2] Pengo V, Tripodi A, Reber G, et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009;7(10):1737–1740
[3] CLSI. Laboratory Testing for the Lupus Anticoagulant; Approved Guideline. CLSI document H60-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2014