What does a negative Lupus Anticoagulant (LA) with a mildly prolonged Activated Partial Thromboplastin Time (APTT) indicate?

From the Guidelines

A mildly prolonged APTT lupus sensitive test with a negative lupus anticoagulant result warrants further investigation to rule out antiphospholipid syndrome or other coagulation abnormalities. This pattern could indicate an early or low-titer antiphospholipid antibody that isn't yet detectable by the LA test, or it might represent a different coagulation abnormality altogether, as suggested by the guidelines for lupus anticoagulant detection 1. Common causes include mild factor deficiencies (particularly factors VIII, IX, XI, or XII), early vitamin K deficiency, mild liver dysfunction, or the presence of unfractionated heparin in the sample. It's also possible this represents a laboratory variation or pre-analytical error. Some key points to consider in the interpretation of these results include:

• Patient selection for LA testing should be based on clinical characteristics, with testing limited to those with a significant probability of having antiphospholipid syndrome (APS) or unexplained prolonged aPTT, as outlined in the guidelines 1.
• The guidelines discourage generalized searches for LA in asymptomatic individuals or categories of patients other than those described, to avoid false-positive results 1.
• For patients with this finding, clinical correlation with any bleeding or clotting symptoms, review of medication history (especially anticoagulants), and consideration of repeat testing in 12 weeks if there's clinical suspicion of antiphospholipid syndrome are recommended.
• If the patient has unexplained thrombosis or pregnancy complications, additional antiphospholipid antibody testing (anticardiolipin and anti-beta2 glycoprotein I antibodies) would be appropriate, as these conditions are associated with a high probability of having APS, according to the guidelines 1. Clinical judgment and correlation with patient symptoms and history are essential in determining the next steps in management, and the mild prolongation alone, without clinical symptoms or other laboratory abnormalities, typically doesn't require treatment but should be documented for future reference.

From the Research

Interpretation of Lupus Anticoagulant Test Results

• When Lupus Anticoagulant (LA) is not detected on testing, but the APTT (activated partial thromboplastin time) lupus sensitive is mildly prolonged, it may indicate the presence of antiphospholipid antibodies (aPL) that are not detected by the LA test 2.
• The APTT test is sensitive to the presence of LA, but it may not detect all types of aPL, which can lead to false-negative results 2.
• A mildly prolonged APTT result may suggest the presence of aPL that are not strong enough to cause a significant prolongation of the APTT, or it may indicate the presence of other coagulation disorders 3, 4.

Clinical Implications

• The presence of aPL is associated with an increased risk of thrombosis, and patients with aPL may require anticoagulation therapy to prevent thrombotic events 3, 4, 5.
• The diagnosis of antiphospholipid syndrome (APS) requires the presence of aPL, as well as clinical manifestations such as thrombosis or pregnancy morbidity 4, 5, 6.
• Patients with aPL may require regular monitoring of their coagulation status, as well as their clinical condition, to prevent thrombotic events and other complications 3, 4.

Laboratory Diagnosis

• The laboratory diagnosis of LA involves the use of multiple tests, including the APTT and the dilute Russell's viper venom test (dRVVT) 2.
• The results of these tests should be interpreted in conjunction with clinical information and other laboratory results to determine the presence of aPL and the risk of thrombosis 2, 6.
• The use of algorithms for LA detection and the expression of results in ratio to reduce inter- and intravariability can help to improve the accuracy of LA testing 2.