Authors’ reply

We thank doctor Tong¹ for the letter regarding our work. We read the comments and reflections on this topic with great interest. As outlined in the original article,² fibrin clot properties were assessed only once at baseline. Given that obstetric antiphospholipid syndrome (OAPS) is a dynamic autoimmune condition, fluctuations in immune activity, inflammatory burden, and prothrombotic / antifibrinolytic alterations are likely to occur over time. Therefore, single‑time‑point measurements may not fully capture the evolving thrombotic risk profile in these patients, which represents a study limitation. Longitudinal studies incorporating repeated assessments of key fibrin measures could demonstrate whether dynamic monitoring of plasma clot properties may improve risk stratification for thromboembolic events, as compared with baseline evaluation alone.

Our study did not aim to examine the influence of different antithrombotic treatment regimens on fibrin clot architecture and fibrinolysis in OAPS during pregnancy. Although standard management with low‑molecular‑weight heparin combined with low‑dose aspirin is widely used in pregnant women with OAPS, 20%–30% of the patients still experience pregnancy‑related complications. Whether treatment modifications, including dose adjustments, prolonged thromboprophylaxis in nonpregnant women with OAPS, or the use of alternative anticoagulants can favorably modify the fibrin clot phenotype is worth further investigation. In line with our data, a recent paper has shown that other coagulation markers, such as thrombin‑antithrombin complexes, can improve risk stratification in OAPS,³ which suggests that, if standardized, some fibrin variables might help optimize the management of OAPS in the future. Overall, further research is warranted to determine the clinical utility of serial fibrin clot assessment and explore whether targeted therapies can reverse the prothrombotic clot phenotype and improve patient outcomes.

Recruitment of women predominantly with a high‑risk antiphospholipid antibody (aPL) profile in a single center may represent selection bias and potentially overestimate the prevalence and prognostic impact of prothrombotic fibrin clot abnormalities. Based on our previous results⁴ for thrombotic APS, heterogeneity of the fibrin clot phenotype is driven in part by the type of aPL profiles. Therefore, multicenter, large‑scale prospective cohort studies are needed to clarify these challenging issues in OAPS. In addition, our study² identified a significant inverse association between antiphosphatidylserine / prothrombin (aPS/PT) antibodies and fibrin clot permeability in women with OAPS, which extends previous observations in thrombotic APS and suggests a potential impact of aPS/PT antibodies on modulating thrombotic risk in OAPS. While this correlation supports the concept that aPS/PT antibodies contribute to the prothrombotic fibrin clot phenotype,⁵ the underlying molecular mechanisms remain poorly understood. It is unclear whether these antibodies directly interact with fibrinogen or prothrombin, alter fibrin polymerization, enhance thrombin generation, or interfere with fibrinolysis. Future experimental studies are warranted to elucidate these pathways.

Together, these considerations underscore that while the current study provides important and clinically relevant insights into fibrin clot abnormalities and thrombotic risk in OAPS, larger studies on OAPS patients with low‑to‑high risk aPL profiles in ethnically diverse populations should be conducted to corroborate and expand our findings. We hope that their results supported by mechanistic studies might lead to optimized management of OAPS.