Quality Analysis of Lupus Anticoagulant Testing: Indeterminate and Interference

Abstract

Abstract Lupus anticoagulant (LA) testing is a commonly performed test within hemostasis laboratories. Criteria for diagnosing a LA based on the International Society on Thrombosis and Hemostasis are: prolonged phospholipid-dependent (PD) clotting test, evidence of an inhibitor, evidence the inhibitor is PD, and exclusion of specific inhibitors. At our academic institution, we analyzed Lupus anticoagulant results to establish common sources of drug interference (DI), identify causes of indeterminate results, and evaluate if repeat testing was performed on patients with an initial indeterminate test. At this institution, Lupus anticoagulant evaluation includes activated partial thromboplastin time (aPTT), Anti-Xa activity, Thrombin Time (TT), diluted Russell Viper Venom Time, hexagonal phase phospholipid assay, and Platelet Neutralization Procedure. Samples with Anti-Xa activity >0.1 IU/mL and/or elevated TT are treated with hepzyme; if the Anti-Xa activity or TT does not correct, testing is not completed. Samples with elevated aPTT undergo an immediate and incubated mixing study (MS). Samples are considered positive (POS) for LA if there is a positive screening test (+ST), +MS, and evidence of PD in at least one assay. Tests are resulted as indeterminate (IND) with a +ST and either +MS or +PD. LA results are reported as unlikely (UNL) if only a single phospholipid panel is positive without +ST or +MS, and negative (NEG) if the ST, MS, and PD assays are all negative. Patients with indeterminate LA testing are recommended to have repeat LA testing after 12 weeks. A total of 3025 cases were identified over the 18-month period (July 2020 – December 2021). The majority of cases were interpreted as NEG (2310; 76%) followed by 8% POS (229), 6% IND (174), and 1% UNL (34). While the majority of IND met the ST (99%) and PD (71%) criteria, only 32% were +MS, indicating failure of an inhibitor detection in the mixing study is the major factor preventing an IND from becoming positive. Within the IND group, only 25% (43) underwent the recommended repeat LA testing. The results of repeated 43 IND tests are as follows: 16 NEG, 4 POS, 19 IND, 3UNL, 1 DI. While a significant proportion of IND repeated testing became negative, a majority remained IND, arguing for more comprehensive LA testing. This quality study demonstrates the majority of patients at this institution who receive an interpretation of IND LA do not undergo the recommended repeat testing, underscoring the importance of follow-up and education to standardize care. Prospective studies maybe needed to elucidate the clinical significance of IND LAs. Additionally, 278 (9%) cases were canceled due to drug interference, the majority (192; 69%) due to direct oral anticoagulants (DOAC). Testing for LA in patients actively receiving DOACs should be discouraged. Alternatively, methods to remove DOAC interference should be standardized.