Appropriate Laboratory Testing for Lupus Anticoagulants: An Observational Study at an Academic, Tertiary Care Hospital

Introduction: Lupus anticoagulants (LA) are a heterogeneous group of immunoglobulins that develop spontaneously, with autoimmune disorders or transiently in association with acute infectious or inflammatory conditions. Transient LA are generally presumed to be harmless, while LA that persist over time may be a risk factor for venous and arterial thrombosis. Accordingly, persistence of LA after a first thrombotic episode may signal a recommendation for long term thromboprophylaxis with an anticoagulant, thus, to guide therapy, correct interpretation of LA test results is paramount. LA test interpretation is complicated, however, and clinicians must understand the LA test characteristics, the importance of timing of testing and the implications of positive, negative and equivocal test results to use the information effectively for clinical decision making. We undertook this study to ascertain how clinicians at our institution approach LA testing and to identify knowledge gaps that may amenable to educational interventions aimed at improving patient care in this area.

Methods: Our laboratory uses a combination of the dilute Russell viper venom time (dRVVT) and silica clotting time (SCT) for LA screening (Instrumentation Laboratories, Bedford MA, USA). A positive test for either dRVVT or SCT is considered positive for LA. Negative tests for both are required to exclude the presence of LA in a given patient. We provide cutoff values for negative, positive and indeterminate test results and recommend repeat testing after 12 weeks for any indeterminate or positive test to establish persistence in accordance with current guidelines. We recommend NOT testing patients who are currently anticoagulated with a direct oral anticoagulant (DOAC) due to the potential for a false positive test result. We retrospectively analyzed 715 completed LA tests between April 1, 2018 and April 30, 2019 to determine the proportion of positive, negative and indeterminate test results. We then reviewed individual patient records to identify patient and provider characteristics and document additional diagnostic actions taken based on the initial test results. We report our findings descriptively.

Results: The average age of patients undergoing laboratory testing for LA was 46.9 years, (median, 47.0 years), with a preponderance of females (73%). The majority of tests were ordered by rheumatology or hematology providers (53%). Anticoagulation with a DOAC was present in 74 (10%). A negative initial test (dRVVT and SCT both negative) was documented in 413 patients (58%), and was repeated in nine individuals (2%) at a second time point. A positive test (dRVVT and/or SCT positive) was documented in 170 (24%), of which 53 (31%) were repeated subsequently and 18 (11%) were themselves repeat tests to follow up on a previous positive test, leaving 99 (58%) initial positive tests that were not repeated. The majority of repeat tests were conducted at a time point <12 weeks after the initial test (n = 37; 70%). Equivocal test results (dRVVT and/or SCT indeterminate) were obtained in 132 patients (18%) and repeated in 25 (19%).

Conclusion: We discovered a surprisingly high rate of inappropriate LA test usage at our institution. The results of this investigation will guide our efforts to develop interventions aimed at informing our clinicians about best practices for laboratory testing for LA, and provide opportunities to leverage the features of the electronic health record to improve test ordering procedures.