Vascular damage correlates between heparin-induced thrombocytopenia and the antiphospholipid syndrome

Antibody-mediated disorders of heparin-induced thrombocytopenia and antipho spholipid antibody syndrome have remarkably similar clinical presentations, both of which can progressively result in severe vascular and thrombotic d isorders. We hypothesized that the mechanism of platelet activation as occu rs in heparin-induced thrombocytopenia may also occur in antiphospholipid a ntibody syndrome particularly at the vascular wall, that endothelial injury may be similar in heparin-induced thrombocytopenia and antiphospholipid an tibody syndrome, and that these alterations may be caused by related antibo dies. Antibody titers and vascular endothelial damage in patients with hepa rin-induced thrombocytopenia and antiphospholipid antibody syndrome were st udied in plasma samples collected from normals (n = 17), heparin-induced th rombocytopenia patients (n = 15), antiphospholipid antibody syndrome patien ts (n = 30), and patients clinically diagnosed with antiphospholipid antibo dy syndrome and heparin-induced thrombocytopenia (n = 8). Diagnosis of hrpa rin-induced thrombocytopenia was confirmed by C-14-serotonin release assay or positive antiheparin-platelet factor 4 antibody titer, and antiphospholi pid antibody syndrome was confirmed by positive anti-beta(2)-glycoprotein ( GP) 1/cardiolipin (IgG or IgM) antibody titer. The antiheparin-platelet fac tor 4 antibody was not detected in any patient with antiphospholipid antibo dy syndrome. Patients with heparin-induced thrombocytopenia did not have el evated IgG anti-beta(2)-GP1 titers, but three (20%) patients had low-positi ve IgM anti-beta(2)-GP1 titers. The endothelial damage markers of soluble t hrombomodulin, soluble P-selectin (p < 0.05 vs. normal), plasminogen activa tor inhibitor-1 and tissue factor were elevated in heparin-induced thromboc ytopenia and antiphospholipid antibody syndrome patients. The soluble E-sel ectin was elevated only in the patients with both heparin-induced thrombocy topenia and antiphospholipid antibody syndrome (p < 0.05 vs. normal). Level s of soluble L-selectin and von Willebrand factor were not different from n ormals. The pathogenesis of heparin-induced thrombocytopenia and antiphosph olipid antibody syndrome appears to be due to two distinct antibodies but a ssociated with similar damage to the vascular endothelium in both diseases.