Clinical audit of antiphospholipid antibody testing in tertiary practice: towards improved relevance in thrombophilia investigations

Abstract

Background: The antiphospholipid syndrome (APS) is an autoimmune condition characterised by vascular thromboses and/or pregnancy morbidity. Diagnosis of APS typically requires laboratory evidence of antiphospholipid antibodies (aPL). Depending on their clinical presentation, affected individuals might be seen by a variety of clinical specialities. Aim: To evaluate clinical ordering patterns for aPL/APS at a tertiary level public facility. Methods: We performed an audit of internal clinical requests for aPL tests at our institution for a 6‐month period. Results: We identified a wide variety of clinical ordering background for aPL, of predominantly obstetric (72/268; 26.9%) or thrombophilic (78/268; 29.1%) patients. Only 11/268 samples (4.1%) were positive for lupus anticoagulant (LA) and 14/268 (5.2%) were positive for anticardiolipin antibody (aCL). The percentage of aCL positivity in the LA‐positive group was 46% (5/11). None of the 72 obstetric patients tested was identified to have aPL. Of the 11 LA‐positive patients, the reasons identified for testing comprised: prolonged Activated Partial Thromboplastin Time (assay) (n= 3), thrombosis (n= 3), APS (n= 2), systemic lupus erythematosus (n= 2), vasculitis (n= 1). Conclusion: We determined a wide variety of clinical ordering background for aPL at a tertiary level institution, with an overall low rate (<10%) of aPL positivity among a hospital population of predominantly obstetric or thrombophilic patients. That no positive obstetric aPL cases were identified suggests local clinical ordering guidelines may need review, as also potentially practised at other institutions. We also observed a moderate rate (46%) of coincidence of aCL and LA, in agreement with guidelines indicating that multiple tests are required to identify APS.

Laboratory Identification of Lupus Anticoagulants

“…In recent audits of practice, some one-third of patients being investigated for thrombophilia-based tests have been determined to be likely on anticoagulant therapy at the time of testing. 17,18 This has significant implications for laboratory testing of LA, as laboratories are likely to be unknowingly testing samples for LA while patients are on VKAs, thereby compromising LA diagnosis, and potentially reporting both false-positive and falsenegative LA test findings.…”

“…Again, laboratories may unknowingly be testing for LA while patients are on heparin anticoagulant therapy, 17,18 thereby compromising LA diagnosis, and potentially reporting both false-positive and false-negative LA test findings.…”

Variability and diagnostic utility of antiphospholipid antibodies including lupus anticoagulants

“…Nevertheless, much remains to be done. For example, we need to train clinicians better in terms of test requests – to avoid inappropriate testing that is both costly and which may lead to false‐positive diagnosis of APS and adverse patient treatments . We also need to develop better assays for APS diagnosis , and additionally, but certainly not finally, to continue to improve harmonization and standardization in laboratory testing for all APS‐associated tests including LA .…”

Trials and tribulations in lupus anticoagulant testing

“…Nevertheless, much remains to be done. For example, we need to train clinicians better in terms of test requests; to avoid inappropriate testing that is both costly and which may lead to false-positive diagnosis of APS and adverse patient treatments [15,16] . We also need to develop better assays for APS diagnosis [12] .…”