Background Overexpression of tissue factor (TF) and activation of the coagulation system are characteristic pathophysiology of antiphospholipid syndrome (APS). Heparanase (HPSE) is an endo-b-D-glucuronidase that cleaves heparan sulfate chains on cell surfaces and in the extracellular matrix and is released primarily from activated platelets. It has been reported that non-enzymatic activity of HPSE participates in the regulation of TF gene expression in endothelial cells and its related coagulation pathway.
Objectives To evaluate plasma HPSE concentration and to determine its association with platelet activation in patients with APS
Methods Plasma samples were collected from 19 clinical APS patients with history of thromboembolic events and/or fetal loss, 16 patients only seropositive for antiphospholipid antibodies (aPL), and 10 normal healthy controls. Plasma levels of HPSE, soluble P- and E-selectin were measured by enzyme linked immunosorbent assay. IgG fractions were purified from the sera of 7 APS patients and healthy subjects. Induction of HPSE release from platelets by APS IgG was confirmed by western blot.
Results Plasma HPSE levels were significantly elevated in APS patients compared to controls (1046.8±240.7 vs. 203.6±87.1 mU/ml, P =0.002) and its levels of clinical APS patients were much higher than those of the patients only seropositive for aPL (1326.0±413.1 vs. 695.7±232.2 mU/ml, P =0.02). Plasma HPSE levels were positively correlated with soluble P-selectin levels (r =0.826, P <0.001) but not with soluble E-selectin levels (r =0.186, P =0.307). Moreover, plasma HPSE levels showed a positive correlation with concentration of anti-b2 glycoprotein I antibody in clinical APS patients (r =0.524, P =0.031). Platelets treated with APS IgG in vitro produced significantly larger amount of HPSE in a dose-dependent manner compared with control IgG.
Conclusions Plasma HPSE levels were elevated in patients with APS and correlate with platelet activation, suggesting a potential role of HPSE in prothrombotic state of APS.
Disclosure of Interest None Declared