Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low antiphospholipid antibody levels

Abstract

Our objective was to determine whether there is a relationship between low antiphospholipid (aPL) antibody levels and the obstetrical complications of antiphospholipid syndrome (APS) and to analyze the impact of conventional APS treatment in patients with low aPL levels. To this end, we retrospectively reviewed the files of all patients referred to our unit (2003–2010) for unexplained pregnancy morbidity, with an aPL test result. We compared patients with APS confirmed by Sapporo criteria (Group 1) with patients with APS-like obstetrical complications with an aPL titer below the intermediate titer (Group 2). Overall, 57 patients were included (25 in Group 1; 32 in Group 2). Obstetrical events were recurrent spontaneous abortion <10th week of gestation (n = 9 patients in Group 1; n = 13 patients in Group 2), fetal death (n = 11 and 16, respectively), preeclampsia (n = 5 in Group 1; n = 6 in Group 2). The total number of obstetrical events per patient was very similar before APS treatment (3 [1–8] in Group 1; 3 [1–6] in Group 2) and decreased significantly after APS treatment to 0 [0–2] and 0 [0–2], respectively (p < 0.05). The incidence of premature births and the characteristics of neonates were similar in the two groups. In this study, treatment of patients with low aPL levels and APS-like obstetrical events was associated with outcomes similar to those found in otherwise normal women with recurrent miscarriage or other adverse events. However, properly designed treatment trials would be required to prove the benefit of such treatments.

Introduction

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic and/or obstetrical complications caused by antiphospholipid antibodies (aPL) (Wilson et al., 1999, Miyakis et al., 2006). Patients tend to present either thrombotic or obstetrical complications, but rarely both (Kist et al., 2008). During the course of the disease aPL levels may vary and even become undetectable (Roubey, 1994). Current revised Sapporo classification criteria consider a diagnosis of APS only when aPL levels are moderate or high, but low antibody levels have been reported in patients with thrombotic complications (Amaral et al., 2010, Dunn et al., 2005). Cases of recurrent early miscarriage and fetal death with intermediate or low aPL levels not meeting the revised Sapporo criteria are increasingly considered as APS in the USA (Branch et al., 2010a, Branch et al., 2010b). Triple positivity (the presence of tree different aPLs) is associated with a significantly higher rate of pregnancy loss in obstetrical APS (Ruffatti et al., 2009). However, a single positive aPL test is more common in purely obstetrical APS than in thrombotic or mixed APS (Boffa et al., 2009).

It is important not to overlook a diagnosis of APS in patients with obstetrical complications as rapid intervention with conventional treatments can much improve pregnancy outcomes (Tuthil and Khamashta, 2009). However, moderate-to-high aPL levels remain the recommended criterion for APS diagnosis even though the APS diagnostic threshold may well prove to be lower during pregnancy (Branch et al., 2010a, Branch et al., 2010b). The aim of this retrospective study was therefore to assess whether the presence of low-titer aPL might be associated with APS-like obstetrical events and to analyze the impact of conventional treatment with aspirin and/or low molecular-weight heparin (LMWH) in patients with low-titer aPL levels. Patients with low antibody levels were compared with a group of patients with confirmed obstetrical APS.