Reviews
Vol. 5 No. 3 (2026): In memory of Armando D’Angelo
Lupus anticoagulant: a never-ending story. New insights from anti-prothrombin antibodies
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 28 August 2026
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Until recently, the lupus anticoagulant (LA) phenomenon was largely attributed to antibodies directed against β2-glycoprotein I (β2GPI). However, this explanation does not account for LA activity in patients with isolated LA, in whom anti-β2GPI antibodies are absent. Increasing evidence indicates that anti-prothrombin (aPT) antibodies play a key role in these cases. In most patients with isolated LA, aPT antibodies detected with the anti-phosphatidyl-serine/prothrombin (aPS/PT) test appear to explain the observed coagulation inhibition. They also represent a major determinant of LA activity in triple-positive patients (LA, aCL, and aβ2GPI). Because false-positive LA results frequently occur in patients receiving oral anticoagulants, detection of aPT antibodies may represent a useful surrogate marker of LA. In vitro, some aPT antibodies can induce activated protein C resistance, contributing to the hypercoagulable state promoted by aβ2GPI antibodies. However, aPT antibodies are also involved in LA/hypoprothrombinemia syndrome, which is a bleeding disorder. In this case, aPT antibodies contribute to causing severe hypoprothrombinemia by promoting rapid prothrombin clearance. These observations suggest three biological patterns of LA: i) procoagulant LA in triple-positive patients at high thrombotic risk, typically associated with high-titer IgG aPT antibodies detected by aPS/PT test. ii) Mildly procoagulant LA in patients with isolated LA, generally associated with moderate-to-high-titer IgM aPT antibodies detected by aPS/PT test. iii) Anticoagulant LA, characterized by very high titers of aPT antibodies detected by aPS/PT test associated with hypoprothrombinemia and bleeding. Recognition of these mechanisms is refining the interpretation of LA and offering novel insights into the pathophysiology of antiphospholipid syndrome.
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How to Cite
1.
Pengo V. Lupus anticoagulant: a never-ending story. New insights from anti-prothrombin antibodies. Bleeding Thromb Vasc Biol [Internet]. 2026 Aug. 28 [cited 2026 Oct. 15];5(3). Available from: https://www.btvb.org/btvb/article/view/469
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