Does seronegative obstetric APS exist? “pro” and “cons”

Antiphospholipid Syndrome (APS) is the commonest treatable cause of recurrent miscarriage and pharmacological treatment of pregnant patients with antiphospholipid antibodies (aPL) should aim at preventing obstetric complications and maternal thrombotic events. Conventional treatment for patients with an established diagnosis of obstetric APS (OAPS), generally resulting in over 70–80% successful pregnancies. Since seropositive (SP)-APS and seronegative (SN)-APS patients had shown similar clinical profiles, patients with SN- OAPS, as well as SP-OAPS, should receive combined treatment in order to improve the pregnancy prognosis; indeed, current standard of care increased good pregnancy outcome in SN-APS, with similar effect to confirmed APS. The above data suggest that there are patients with the clinical manifestations of OAPS but persistently negative to conventional aPL that need to be identified to ensure adequate therapy and therefore a better prognosis. The clinical utility of non-criteria aPL in the diagnosis of SN-APS is still a matter of debate. In the last decade more and more studies have reported the presence of patients suffering from SN-APS in which non-conventional (“non-criteria”) aPL might be present or antibodies may be detected using methodological approaches different from the traditional assays. To improve test standardization large prospective, multicenter, and multinational studies are needed. Therefore, when assessing a patient with clinical manifestations consistent with OAPS but aPL negative using the conventional available assays, the clinician should consider the possibility that the patient is affected with SN-APS.