Identification of thrombin antibodies in patients with antiphospholipid syndrome

Venous or arterial thrombosis, abortion, and the presence of antiphospholipid antibodies (aPL) define the criteria for the antiphospholipid syndrome (APS). A heterogeneous group of antibodies against phospholipids and plasma proteins may influence several coagulation pathways and lead to thrombophilia. We investigated the presence of antibodies to thrombin (Thr) in patients with aPL and reviewed their clinical manifestations. IgG and IgM titers of aPL were measured by ELISA (Aesku.Diagnostics, Wendelsheim, Germany). Lupus anticoagulants (LA) were measured according to the criteria of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. One hundred twenty patients were identified with LA or anticardiolipin (aCL). Of the 120 patients, 98 (82%) had primary APS and 22 (18%) had secondary APS. Further, 76/120 (63%) were suffering from thromboembolic manifestations, mostly venous thrombosis. Anti-thrombin-IgG was detected in 20%, and anti-thrombin-IgM was detected in 23% of the patients. The presence of anti-thrombin antibodies was closely related to the presence of anti-beta(2)-glycoprotein-I (beta(2)-GP-I) (96%), aCL (97%), and LA (87%), and less well to the presence of anti-phosphatidylserine/prothrombin (Ser/Pro) antibodies (71%) or anti-prothrombin antibodies (Pro) (50%). Sixty-seven percent of the patients with anti-Thr-IgG suffered from thromboembolic complications, mostly arterial thrombosis. The rate of thrombosis was higher for these patients than for patients with anti-beta(2)-GP-I antibodies (37/60, 62%), LA (50/79, 63%), or anti-Ser/Pro antibodies (18/28, 64%). Anti-thrombin antibodies were found in 20% of patients with aPL; 67% of these patients were admitted with thrombotic manifestations of APS. The presence of anti-thrombin antibodies was closely associated with the presence of aCL and anti-beta(2)-GP-I antibodies. The sensitivity of the test for anti-thrombin antibodies for the diagnosis of APS was higher than the sensitivity of the anti-prothrombin assay and similar to the sensitivity of the anti-Ser/Pro assay.