Presented at the ISTH 2026 Congress in Paris and simultaneously published on Thrombosis Research, the results of the START2 observational study describe five hundred patients with persistently positive antiphospholipid antibodies (aPL) followed in major Italian Thrombosis Centers (1).

Of particular interest are the patients, approximately one‑third of the cohort, with confirmed persistent positivity for one or more aPL in the absence of clinical manifestations typical of antiphospholipid syndrome (APS) (2,3). These “carriers” represent a group whose clinical course and therapeutic management remain subject to several open questions.

Patients were included only if they had both a baseline measurement and a repeat assessment after at least 12 weeks of all three antiphospholipid antibody types: lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti‑β2‑glycoprotein I antibodies (aβ2GPI). A total of 341 individuals were classified as having APS, while 159 were categorized as carriers.

Antibody Profile Distribution

The distribution of antibody profiles did not differ between APS patients and carriers. Triple positivity was observed in the majority of cases in both groups (43% vs 44%), while double positivity was found in 13% vs 12%. In only a few cases did isolated aCL positivity, or even more rarely isolated aβ2GPI positivity, remain confirmed at follow‑up.

“Persistent isolated aCL or aβ2GPI positivity was rare, showing that isolated results, especially at low titers, often fail to persist over time and therefore may represent false positives,” explained Professor Vittorio Pengo, coordinator of the START2 antiphospholipid registry.

In contrast, isolated LA positivity was relatively common, present in 23% of APS patients and 30% of carriers. Within this cohort, APS patients with isolated LA positivity exhibited the highest prevalence of venous thromboembolism (67%), even exceeding those with triple positivity (50%).

“This observation is consistent with the notion that LA activity often reflects anti‑phosphatidylserine/prothrombin (aPS/PT) antibodies, which have been shown to induce acquired activated protein C resistance and promote venous thrombosis,” -the authors noted.

Nevertheless, accurately diagnosing LA, while avoiding false positives and false negatives, remains a challenge for laboratories, despite recent ISTH recommendations (4).

Arterial thromboses were more evenly distributed across the different serological profiles (single, double, or triple positivity), suggesting that traditional cardiovascular risk factors continue to play a determining role in arterial manifestations ofAPS.

Patient Treatment

Most patients (62%) who experienced a venous thromboembolism (VTE) episode were treated with warfarin. A minority received direct oral anticoagulants (DOACs), often due to uncertainties regarding optimal therapy or difficulties—or refusal—by patients to take warfarin. Surprisingly, 11% of VTE patients were treated with aspirin (ASA).

Treatment of patients with arterial thrombosis was also highly heterogeneous, reflecting current uncertainties, particularly in scenarios where the attribution of thrombosis to APS is unclear. Specifically, 51% of patients were treated with warfarin, 37% with ASA, and sporadic cases with DOACs or other agents.

Approximately half of the carriers, especially those with high‑risk sierological profiles such as triple positivity, received aspirin as primary prophylaxis.

Work in Progress…

Upcoming follow‑up data from the START2 registry will provide important insights into the clinical course of these patients, particularly carriers, and into the outcomes of different therapeutic strategies.

 

If you wish to contribute to the advancement of research carried out by Arianna Anticoagulation Foundation, we invite you to do so through the following link: Support the research initiatives of Arianna Anticoagulation Foundation

 

References

  1. Pengo V, Poli D, Sarti L, et al.  Descriptive analysis of the Nationwide START2 antiphospholipid registry: Clinical and laboratory characteristics of patients with persistently positive antiphospholipid antibodies. Thrombosis Research 2026. https://doi.org/10.1016/j.thromres.2026.109786.
  2. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of
    the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost.
    2006;4:295–306.
  3. Barbhaiya M, Zuily S, Naden R, et al. 2023 ACR/EULAR antiphospholipid syndrome
    classification criteria. Ann Rheum Dis. 2023;82:1258–1270.
  4. Devreese KMJ, de Groot PG, de Laat B, et al. Updated guidelines for lupus anticoagulant detection. J Thromb Haemost. 2020;18:2828–2839.

 

Warning: The information on anticoagulazione.it is for informational purposes only and does not replace the advice of your doctor. Always consult a doctor before making any decisions about your health.

AVVERTENZA: Le informazioni contenute nel sito anticoagulazione.it hanno scopo puramente informativo e non sostituiscono il parere del medico. Consulta sempre un medico prima di prendere decisioni sulla tua salute