Lupus Anticoagulant (LA) Evaluation with Reflex

When the test is ordered, 2 different coagulation pathways are screened: PTT-LA and dRVVT. If the screening test is prolonged, it reflexes to a confirmatory test; if that test is positive, it reflexes to a mixing study.

LAs are heterogenous antibodies that differ in titer, avidity, and isotype. This is why the International Society of Thrombosis and Haemostasis (ISTH) recommends using 2 different reagents that evaluate different coagulation pathways (PTT-LA–intrinsic pathway, dRVVT–common pathway) to increase the sensitivity of detection.¹ If LAs are detected using either reagent, the test is positive.

For warfarin, the screening tests (PTT-LA, dRVVT) may be prolonged, but the confirmatory tests are fairly good at distinguishing LA from the warfarin effect. However, to be absolutely sure that warfarin is not interfering in the testing, it is recommended to hold warfarin for 2 weeks, if possible, prior to testing.²

For unfractionated heparin, the Hexagonal Phase and dRVVT tests have heparin neutralizers. At very high levels, it is possible to overwhelm the neutralizing capacity, resulting in false-positive confirmatory studies. Expect the PTT-LA to be markedly prolonged.

However, many experts, including the Scientific Subcommittee (SSC) of ISTH on lupus anticoagulant, recommend not testing patients for LA while anticoagulated.¹ However, if needed, heparins/low-molecular-weight heparins may be held for at least 24 hours before testing to minimize heparin interference.² Note that testing is not recommended during emergent situations, which includes acute thrombosis. Also, testing should be performed after completion of initial therapy and if it might change management strategies. This is true for thrombophilia testing in general beyond LA testing.

The designation of "weak" LA is based on the observation that the Hexagonal Phase Confirm result is just above the cut-off for positivity. This is a laboratory finding only and does not indicate a lower potential to cause a thromboembolic event.

Yes, false-positive LA results may occur when patients are taking either factor Xa inhibitors or direct thrombin inhibitors. If a patient is known to be taking one of these medications at the time of specimen collection, the LA test result should be considered indeterminate.

If possible, for patients who are on direct oral anticoagulants (eg, rivaroxaban, apixaban), Anticoagulation Forum recommends holding these medications for 48 hours and then testing for LA to minimize the effect of these medications.²

See the Quest Diagnostics Nichols Institute publication, “Bleeding and Thrombosis: Better answers from high-quality testing.”