Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study

The pathogenesis of antiphospholipid antibody (aPL) related thrombosis is m ultifactorial and includes, amongst others, enhanced coagulation activation measured as prothrombin fragment 1 + 2 (F1 + 2), elevated plasma levels of von Willebrand factor (vWF), plasminogen activator inhibitor (PAI) and end othelin-1 (ET-1) as well as heightened thromboxane generation and lipid per oxidation. To evaluate the antioxidant susceptibility of some of the above pathways, probucol (500 mg/d orally, a cholesterol lowering agent bearing a ntioxidant properties) was administered for a three week period to 14 subje cts with aPL and to seven healthy controls. At baseline aPL participants sh owed higher plasma levels of vWF (P = 0.006), ET-1 (P = 0.0002) and enhance d urinary excretion of 11-dehydro-thromboxane-B-2 (TXB2) (P = 0.0004), F2-i soprostanes (marker of lipid peroxidation) (P = 0.02) and albumin (P = 0.04 ) than controls. In the aPL group baseline IgG anticardiolipin (aCL) titre positively related with urinary TXB2 (r(2) = 0.43, P = 0.01) and inversely with urinary NOx (r(2) = -0.6, P = 0.005) whereas urinary NOx and TXB2 were negatively correlated (r(2) = -0.42, P = 0.01). After the treatment period significant decreases from baseline values were noted for PAI (P = 0.01), ET-1 (P = 0.006), TXB2 (P = 0.02), F2-isoprostanes (P = 0.01) and albuminur ia (P = 0.01) in aPL participants but not in controls. These pilot data sup port oxidative sensitive mechanisms and a potential role for antioxidant tr eatment in the pathogenesis of aPL induced vasculopathy.