Acquired activated protein C resistance is associated with the co‐existence of anti‐prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus

Summary. Venous thromboembolism (VTE) is one of the common manifestations in the anti‐phospholipid (aPL) syndrome. We examined the levels of IgG antibodies (Abs) to β2‐glycoprotein I (β2‐GP I) and prothrombin, lupus anticoagulant (LA) activity, activated protein C resistance (APC‐R), and factor V Leiden in 96 patients with systemic lupus erythematosus (SLE); 19 with VTE and 77 without VTE. Acquired APC‐R, which was not found in any patient with the factor V Leiden mutation, was present in 33 (34·4%) out of the 96 patients with SLE. The presence of acquired APC‐R was a strong risk factor for VTE. The SLE patients were divided into four groups according to the results of enzyme‐linked immunosorbent assay (ELISA) and LA activity for each aPL Abs: ELISA+, LA+; ELISA+, LA–; ELISA–, LA+; and ELISA–, LA–. A significant association was observed between APC‐R and the co‐existence of anti‐β2‐GP I Abs and LA activity or of anti‐prothrombin Abs and LA activity. There was no association between APC‐R and the presence of anti‐β2‐GP I Abs, anti‐prothrombin Abs, or LA activity alone. However, when multivariate logistical regression analysis was performed, it was clear that only the co‐existence of anti‐prothrombin and LA activity was a significant risk factor for APC‐R. These findings indicate that the co‐existence of anti‐prothrombin Abs and LA activity may be an important factor in the pathogenesis of acquired APC‐R in patients with SLE.