Reclassification of obstetric antiphospholipid syndrome under the 2023 ACR/EULAR criteria: risk of under-recognition in patients with non-criteria antibodies and clinical implications

Abstract

Objective To characterize the clinical, serologic, and treatment features of patients with obstetric antiphospholipid syndrome (OAPS), determine the proportion meeting the laboratory domain of the 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria, and examine patients identified through non-criteria antibodies. Methods We retrospectively reviewed consecutive women with a prior clinical diagnosis of OAPS at our center and assigned de-identified codes P1-P45. Of the 45 patients, 41 had sufficiently complete historical serologic documentation for laboratory-domain reclassification; P10, P17, P34 and P42 were retained in the descriptive cohort but treated as not assessable in the evaluable-case analysis. Two investigators independently scored each evaluable patient across the six clinical domains and two laboratory domains; classification required a cumulative score of ≥3 in both the clinical and laboratory domains. For patients with concomitant systemic lupus erythematosus (SLE), obstetric or hematologic manifestations attributable to SLE were excluded from APS scoring. Results A total of 45 patients were included, all female, with a mean age of 33.7 years (43 primary APS, 2 SLE-associated). Thirty-two patients (71.1%) had a history of pregnancy loss, and 20 had recurrent miscarriage. Anticardiolipin (aCL) IgG and IgM were positive in 9 and 14 patients, respectively; anti-β2-glycoprotein I (anti-β2GPI) IgG and IgM were positive in 2 and 16 patients, respectively; lupus anticoagulant (LAC) was positive in 2 patients. Fourteen patients (31.1%) carried non-criteria antibodies, including 7 with non-criteria antibodies only. Among the 41 patients with evaluable serologic data, 7/41 (17.1%) definitively met the ≥3-point laboratory threshold and 11/41 (26.8%) met it under the upper-bound assumptions. In the conservative sensitivity analysis, which counted P10, P17, P34 and P42 as below threshold, the corresponding estimates were 7/45 (15.6%) and 11/45 (24.4%). Patients with isolated IgM positivity, IgA-only antibodies, single-positive LAC, or non-criteria antibodies alone did not meet the threshold. An exploratory comparison found no statistically significant difference in documented standardized intervention between live-birth and further-loss cases [28/36 [77.8%] vs 6/9 [66.7%]; two-sided Fisher's exact p = 0.666]. Conclusion In this single-center retrospective series of 45 patients, many patients were identified through non-criteria antibodies or low-weight serologic profiles and therefore did not meet the 2023 laboratory-domain threshold. Because of the small sample, these findings are descriptive and hypothesis-generating and should not be generalized. Nevertheless, they support using the 2023 criteria primarily to define homogeneous research cohorts rather than as a stand-alone basis for diagnosis or treatment decisions. Whether the obstetric phenotype requires a separate classification approach remains to be determined.