October 2026 QQ: Anti-Phospholipid Antibody Summary

Our October 2026 quiz, with 32 respondents, asked, “Which is NOT an antiphospholipid antibody?” The answers reveal participants’ wisdom:

1. Anti beta-2 glycoprotein 1: 1 (3%)
2. Alpha-2 antiplasmin: 23 (72%)
3. Lupus anticoagulant: 1 (3%)
4. Antiprothrombin: 7 (22%)
5. Anticardiolipin: 0

The only mislead that attracted respondents was antiprothrombin, a relatively rare APL that is associated with bleeding. Here is an open-access review of APL that references the antiprothombin antibody: Koike T. Comprehensive review of antiphospholipid syndrome: over four decades of advances and challenges. Cells. 2026;15(4):356. doi: 10.3390/cells15040356. PMID: 41744799; PMCID: PMC12939018.

Abstract

Antiphospholipid syndrome (APS), first described in 1983, is a systemic autoimmune disorder characterized by recurrent arterial and venous thrombosis, pregnancy complications, and persistent antiphospholipid antibodies (aPL). Over four decades, significant advancements have been made in understanding APS pathogenesis, diagnostics, and treatment. Key discoveries include the development of standardized anticardiolipin antibody (aCL) assays, the identification of β2-glycoprotein I (β2GPI) as a critical cofactor, and the elucidation of the “two-hit” hypothesis, which explains thrombotic events through a combination of aPL-induced prothrombotic priming and secondary external triggers. Recent research has highlighted the roles of complement activation, neutrophil extracellular traps (NETs), and genetic predispositions shared with systemic lupus erythematosus (SLE). Innovations like the antiphospholipid score (aPL-S) and updated classification criteria, including the 2023 ACR/EULAR guidelines, have improved diagnostic precision and risk stratification. Despite these advances, challenges remain in assay standardization and addressing seronegative APS. Future directions emphasize the integration of multimodal biomarkers, precision diagnostics, and targeted therapies aimed at complement and NET pathways. These efforts aim to achieve individualized care, improving outcomes for APS patients through harmonized diagnostics, mechanistic therapeutics, and data-driven approaches. This review underscores the evolving understanding of APS and its potential for personalized management strategies.

From the Review: Antiprothrombin Antibodies and Coagulation Interference

Antiprothrombin antibodies, another important component of the aPL repertoire, bind to prothrombin when exposed on immobilized phosphatidylserine surfaces (phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT)), recognizing neo-epitopes generated by conformational changes in the protein [9].

Monoclonal aPS/PT antibody 231D exhibits robust LA activity and potently inhibits thrombin generation under defined experimental conditions [13]. These studies emphasize the importance of assay context, antigen conformation, and phospholipid presentation in detecting and interpreting LA phenomena, providing mechanistic insight into how aPS/PT disrupts normal coagulation cascades [10,11,12,13,14].

aPS/PT correlate strongly with LA activity [9,10] and, when combined with anti-β2GPI domain I antibodies (as described later), can significantly improve diagnostic accuracy and risk stratification, particularly in patients with ambiguous serologic profiles or apparent seronegative disease. These developments support a multimarker diagnostic approach that reflects the antigenic heterogeneity of APS.

Further, our informative PowerPoint module, Antiphospholipid Antibodies & Lupus Anticoagulant, includes a brief reference to antiprothrombin antibodies.