Diagnosing Antiphospholipid Antibody Syndrome

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-β₂-glycoprotein-I (aβ2GP1) 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 β2GP1-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 (aβ2GP1, anti-annexin V, antiprothrombin) had significantly higher risks for thromboses and miscarriages than did participants with only one positive value.