This descriptive study, in which we analysed aPL‐positive registry patients using the 2006 revised APS classification criteria, demonstrates that the revised criteria are more stringent than the original version. The study also supports the consensus statement's emphasis on the importance of the identification of the non‐criteria aPL features and non‐aPL thrombosis risk factors in patients with APS.
Of the 144 aPL‐positive patients who met the laboratory requirement of the 1999 original classification criteria, only 59% met the laboratory requirement of the 2006 revised classification criteria, resulting in a more selective aPL‐positive patient population. Thus, we believe that the revision of the original APS classification criteria is a step towards formulating a comprehensive, yet selective and risk‐stratified framework for APS research.
Five patients in the study did not meet the 1999 original classification criteria, but did meet the revised 2006 classification criteria, because of isolated aβ2
GPI positivity; four of these patients had APS and one was asymptomatic. The design of this study did not allow us to determine whether the inclusion of the aβ2
GPI in the revised criteria would increase the overall number of patients who fulfil the APS classification. However, in another retrospective study of 107 patients by Pourrat et al
there was a 6% increase in the number of patients who met the revised criteria, when compared with the 1999 version, where persistent aβ2
GPI antibody titres were taken into account.
Definitions for the non‐aPL features are new to the revised 2006 criteria, with the hope that their clinical and prognostic significance will be better defined in future APS research. In this cohort, non‐aPL features were more common in patients with APS with vascular events. The definitions for the non‐aPL features are based on expert consensus, and for the most part were consistent with usual clinical practice. However, we found the definition for aPL‐associated cardiac valve disease quite rigorous, as the interpretations of the echocardiograms are to be carried out by two expert echocardiographers. As this study was performed at an academic centre, echocardiogram reports that were evaluated by both a fellow and an attending physician were considered adequate.
Almost half of the patients with vascular events had at least one identifiable non‐aPL thrombosis risk factor at the time of their vascular events. This is comparable with the study by Giron‐Gonzalez et al
which found that half of the patients with APS had other non‐aPL thrombosis risk factors at the time of their events. Thus, this study further supports the “second hit”8
hypothesis and the important role of non‐aPL thrombosis risk factors in the development of thrombosis in aPL‐positive patients. We believe that the identification of the thrombosis risk profile, as strongly encouraged by the revised classification criteria, will help better risk stratify aPL‐positive patients in both research and clinical practice.
This study is limited by the usual constraints of a retrospective data analysis, but, as the patients were part of the aPL/APS registries at an academic institution, detailed information, including laboratory data, was available for analysis. The selection bias could not be excluded, as the study population was (1) composed of aPL‐positive patients who agreed to participate in aPL/APS registries in one academic centre and (2) under‐represented for certain ethnic groups. The inclusion criteria of aPL/APS registries were mostly based on aCL and/or LA positivity; thus, the contribution of the newly added “aβ2GPI positivity” in APS diagnosis could not be determined accurately. Finally, the inclusion of asymptomatic aPL‐positive patients who did not fulfil the APS classification criteria could be viewed as a limitation; however, we believe that inclusion of these asymptomatic patients provided useful information, as these patients are relatively common in clinical practice. Also, given that most changes in the criteria are regarding laboratory requirements, analysis of the laboratory data of asymptomatic aPL‐positive patients provided pertinent information.
In summary, we believe that the revised version of the classification criteria will have positive implications in APS research by limiting the inclusion of a heterogeneous group of patients and providing a risk‐stratified approach for evaluating them. Furthermore, although the APS classification criteria are not meant for clinical purposes, they are the best available tool to avoid overdiagnosis of APS in clinical practice.