Lupus anticoagulant (LA) is an autoantibody mistakenly produced by the immune system. It belongs to the group known as antiphospholipid antibodies (aPLs) and its presence is associated with a significantly increased risk of developing blood clots. Although named an “anticoagulant,” LA actually promotes clotting inside the body. LA is a key laboratory finding that often indicates an underlying condition requiring further investigation.
Understanding the Name and Mechanism
The name “lupus anticoagulant” is based on historical misnomers. The “lupus” designation originated because the antibody was first discovered in patients with Systemic Lupus Erythematosus (SLE). However, most people who test positive for LA do not have SLE, and the antibody can appear temporarily following an infection or in other autoimmune conditions.
The “anticoagulant” label is paradoxical because LA promotes clotting (thrombosis) inside the body. This confusing designation stems from how the antibody behaves in vitro (in laboratory clotting tests). In these tests, the LA autoantibody interferes with the chemical reagents, which contain low amounts of phospholipids, resulting in a prolonged clotting time.
The true biological activity (in vivo) involves LA binding to proteins, primarily Beta-2-glycoprotein I, that are attached to phospholipids on cell surfaces. The binding of LA to these complexes disrupts the normal regulation of clotting. This interference makes platelets more prone to activation and aggregation, driving the body toward a pro-thrombotic state and increasing the likelihood of forming dangerous blood clots in both veins and arteries.
Clinical Significance and Related Conditions
The presence of persistent lupus anticoagulant is a primary laboratory criterion for diagnosing Antiphospholipid Syndrome (APS). APS is an acquired autoimmune disorder characterized by recurrent blood clots (thrombosis) and complications during pregnancy. Diagnosing APS requires at least one clinical event, such as a thrombotic episode or recurrent miscarriage, alongside the persistent presence of LA or other antiphospholipid antibodies.
The presence of LA is associated with a high risk of serious health consequences. Clots can occur in deep veins, leading to deep vein thrombosis (DVT), or travel to the lungs, causing a pulmonary embolism. Arterial clots can also form, potentially causing a stroke or a heart attack.
For pregnant individuals, LA significantly increases the risk of complications, known as obstetric morbidity. These complications include recurrent miscarriage, stillbirth, and severe preeclampsia. This is thought to involve clotting in the placenta’s blood vessels. LA can occur as a primary condition or secondarily in patients who also have Systemic Lupus Erythematosus (SLE).
Laboratory Testing for Detection
Detecting lupus anticoagulant is a complex, multi-step process involving three distinct phases. The testing protocol follows established international guidelines.
Screening Test
The first phase uses a coagulation assay sensitive to phospholipids, such as the dilute Russell viper venom time (dRVVT) or activated partial thromboplastin time (aPTT). A prolonged clotting time in this initial screening suggests the possible presence of an inhibitory substance like LA.
Mixing Study
The second phase is a mixing study performed to rule out a deficiency in a specific clotting factor. The patient’s plasma is mixed with normal plasma. If the clotting time remains prolonged, it confirms the presence of an inhibitor like LA; if the time corrects to normal, the issue is likely a factor deficiency.
Confirmatory Test
The third phase proves the inhibitory effect is dependent on phospholipids. This test repeats the original screening but adds a high concentration of excess phospholipids to the plasma. If the prolonged clotting time significantly shortens or “corrects” with the added phospholipids, it confirms the LA antibody was binding to the original low-concentration phospholipids. For a definitive diagnosis, the abnormal result must be confirmed on a separate occasion, typically 12 weeks after the initial positive result.
Managing Lupus Anticoagulant
Management of lupus anticoagulant focuses on preventing the serious thrombotic events associated with its presence. For patients diagnosed with APS who have experienced a blood clot, the standard approach involves therapeutic anticoagulation. Vitamin K antagonists, such as warfarin, are the established treatment, aiming to maintain the International Normalized Ratio (INR) within a therapeutic range, usually 2.0 to 3.0 for venous clots.
A higher INR target or the addition of low-dose aspirin may be considered for patients with recurrent clots or arterial thrombosis. Direct oral anticoagulants (DOACs) are used in certain circumstances, though their effectiveness in high-risk APS patients is still under evaluation. Anticoagulation is often continued indefinitely to prevent future episodes.
In pregnant individuals with a history of APS-related thrombosis, the protocol involves a combination of low-dose aspirin and prophylactic or therapeutic doses of heparin. Heparin is preferred over warfarin during pregnancy because it does not cross the placenta. For individuals who have LA but have never experienced a blood clot, low-dose aspirin may be recommended as a preventative measure, especially if they have other risk factors.