Antiphospholipid syndrome (APS) is a unique disorder at the crossroads of autoimmunity and thrombosis.¹ Traditionally, it has been divided into 2 main phenotypes: thrombotic APS, characterized by recurrent venous or arterial events, and obstetric APS (OAPS), defined by recurrent pregnancy morbidity.² Although this distinction remains clinically useful, it is increasingly clear that both forms share pathophysiological mechanisms that extend beyond pregnancy. Understanding how OAPS may evolve into a prothrombotic state remains one of the key unanswered questions in the field.

In this issue of Polish Archives of Internal Medicine, Piróg et al³ published a study involving 62 women with OAPS and 62 matched controls who had comparable obstetric complications but were negative for AP antibodies. Using established assays, the authors analyzed fibrin clot permeability (K_s) and clot lysis time (CLT), which reflect clot architecture and fibrinolytic resistance, respectively. In the OAPS group, K_s was lower by 16%, and CLT longer by 17% than in the controls, suggesting a more compact and less lysable fibrin network. Thus, this “prothrombotic clot phenotype,” previously described in thrombotic APS,⁴ also characterizes women with purely obstetric manifestations. Importantly, the risk was not homogeneous. The individuals with lupus anticoagulant positivity or a high‑risk AP antibody profile (triple or double positivity) displayed the most impaired fibrin structure and fibrinolysis. During follow‑up, 16% of the OAPS patients developed the first venous or arterial thromboembolic event, a rate (3.6/100 patient‑years) consistent with previous cohort studies. Those who later developed thrombosis had lower baseline K_s (–17%) and prolonged CLT (+12%), suggesting that fibrin architecture may serve as a biomarker of a future thrombotic risk in that setting. In a multivariable analysis, a reduced K_s (≤6.1 × 10^–9cm²) independently predicted thromboembolism.

Over the past 2 decades, the research group led by Professor Anetta Undas has been at the forefront of research on fibrin clot structure and its clinical implications.⁵ Their earlier studies demonstrated that compact, poorly lysable fibrin networks are present in patients with venous thromboembolism,⁶ myocardial infarction,⁷ and other prothrombotic conditions.⁸ In thrombotic APS, this phenotype may be associated with recurrent thrombosis despite adequate anticoagulation.⁹ The current work extends these findings to OAPS, suggesting that fibrin‑related mechanisms contribute to the continuum of APS phenotypes. From a clinical point of view, these results suggest that OAPS may represent a subclinical prothrombotic state. While the current management focuses on preventing pregnancy morbidity with low‑dose aspirin and low‑molecular‑weight heparin, 20%–30% of women still experience adverse outcomes despite therapy,¹⁰ and some later develop thrombosis.¹¹ The identification of laboratory markers, such as reduced K_s or prolonged CLT, could eventually refine risk stratification and guide more personalized long‑term management. Yet, translating these findings into clinical practice requires caution. Fibrin clot permeability and lysis assays are technically demanding and time‑consuming, not widely available, and currently lacking standardization.^12,13 Before they can serve as biomarkers, multicenter validation and technical harmonization are essential. From a mechanistic perspective, this study supports the concept that the thrombotic risk is driven by qualitative abnormalities in fibrin structure, rather than fibrinogen concentration alone. This paradigm aligns with accumulating evidence in cardiovascular medicine, showing that altered fibrin architecture and impaired fibrinolysis are common denominators in diverse prothrombotic conditions, from diabetes to venous thromboembolism.⁵ It could also open the door to fibrin‑modulating therapies, such as with statins, and might represent adjunctive options for patients with a persistently prothrombotic clot phenotype.¹⁴

Beyond its technical results, this study invites us to reconsider the division into obstetric and thrombotic APS. Instead of being 2 separate entities, they may represent different stages of a single disease spectrum, where prothrombotic alterations in fibrin architecture act as an early marker of systemic involvement. In this sense, the work by Piróg et al³ elegantly bridges clinical observations and pathophysiology.