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Diagnosing Antiphospholipid Antibody Syndrome

Results of this study confirmed that aß2GP1 antibodies predicted APS, but the usefulness of aCL as a predictor was not verified.

Antiphospholipid antibody syndrome (APS) is characterized by venous and arterial thromboses and, in women, recurrent miscarriages. Laboratory criteria for diagnosis, recently established at an international workshop, include (in addition to the presence of lupus anticoagulant [LAC] activity) anticardiolipin antibody (aCL) at high titer (>40 IgG or IgM units) on two occasions at least 12 weeks apart, or anti-ß₂-glycoprotein-I (aß2GP1) antibodies at high titer (>99th percentile) on two occasions at least 12 weeks apart (J Thromb Haemost 2006; 4:295). But how well do these tests function in clinical practice?

Investigators from 26 institutions in five countries enrolled 112 patients (median age, 42; 88% women) with persistent LAC levels, high-titer aCL levels, or both, and determined the association of these and other antibodies with objectively documented venous and arterial thromboses and obstetric events. At the time of enrollment, 87 patients had experienced adverse clinical events; during a median follow-up of 3.7 years, 15 patients had new thromboses or miscarriages. Antibodies against ß2GP1-IgG were associated with a 3- to 4-fold higher probability of thrombosis, a 10-fold higher risk for miscarriage, and a 16-fold higher risk for APS. Conversely, no significant associations were observed for high levels of aCL or any IgM antibodies. The researchers noted that anti-annexin V antibodies were associated with a 9-fold increased risk for miscarriage, and antiprothrombin antibodies were associated with a 3- to 4-fold higher risk for thrombosis and a 4-fold higher risk for full APS. Those patients with positive tests for both LAC activity and one or more of the antibodies (aß2GP1, anti-annexin V, antiprothrombin) had significantly higher risks for thromboses and miscarriages than did participants with only one positive value.

Comment: This large study of patients with APS confirms that testing for LAC activity and aß2GP1-IgG antibodies is useful for predicting venous and arterial thromboses and recurrent miscarriages. In addition, implementation of tests for anti-annexin V and antiprothrombin antibodies should be a high priority. Conversely, testing for aCL and any IgM antibodies could be omitted. Furthermore, the current practice of prescribing anticoagulants for patients with high aCL levels but no thromboses or miscarriages should be abandoned. Almost all patients in whom APS is suspected now are tested for aCL, so confirming the results of this study will be very important.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology September 11, 2007

Citation(s):

Galli M et al. Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood 2007 Aug 15; 110:1178-83.

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