Does seronegative antiphospholipid syndrome really exist?

The diagnosis of seronegative (SN-) antiphospholipid syndrome (APS) has been suggested for patients with clinical manifestations indicative of APS but with persistently negative results in the commonly used assays to detect anti-cardiolipin (aCL) antibodies, anti-beta 2 Glycoprotein I antibodies (a beta 2GPI), and lupus anticoagulant (LA). To date the best management of these patients is still unclear. New emerging anti-phospholipid (aPL) assays could improve our ability in diagnosing APS. However, the availability of aPL assays in routine laboratory practice is limited. In fact, even a beta 2GPI is routinely tested in only a small number of laboratories, and other aPL, such as anti-prothrombin or anti-annexin antibodies, in only a few research laboratories. On the other hand transient or false negative aPL assay and other genetic or acquired pro-thrombotic conditions can further complicate this issue. This paper is focused on the arguments for and against the diagnosis of SN-APS and is aimed to help the clinician when approaching a patient with clinical manifestations consistent with APS diagnosis but with negative aPL using the commonly available tests. (C) 2011 Elsevier B.V. All rights reserved.