title: Thromboagglutination by anticardiolipin antibody complex in the antiphospholipid syndrome: a possible mechanism of immune-mediated thrombosis.
abstract: The tendency for patients with antiphospholipid syndrome (APLS) to thromboembolism and the criteria for its detection are well established, whereas the mechanism of this thrombophilic syndrome is still obscure. Using immunofluorescent techniques and a microscopic spontaneous platelet aggregation test (mSPAT), we have previously demonstrated platelet binding by antibody followed by aggregation in patients with lupus anticoagulant. In the present study, we investigated 18 anticardiolipin antibody-positive (ACLA pos.) patients, comprised of 12 primary APLS and 6 secondary APLS lupus patients. We demonstrated direct platelet microaggregate formation in 16/18 cases, whereas this finding was not present in 20 ACLA-negative (ACLA neg.) subjects (P<.001). Indirect testing revealed 10/12 cases of platelet microaggregation and none in the ACLA neg. subjects. In addition, immunofluorescent studies showed that platelet antibody complex binding occurred in 8/12 cases tested directly and in 11/12 cases in indirect testing, as compared to 1 out of 20 binding in ACLA neg. subjects (P<.001). Antibody complex binding was inhibited in two cases by prior extraction of phospholipids. Platelet aggregation could be demonstrated in two ACLA neg. individuals by the addition of exogenous ACLA to platelets in EDTA-plasma. We therefore propose a mechanism for immune-mediated thrombosis in APLS in which calcium-independent platelet aggregation, or thromboagglutination, is initiated by an ACLA-phospholipid complex present in the patients' plasma. Following the antibody complex-induced platelet agglutination, thrombosis proceeds by release, recruitment, and fibrin formation. The mechanism should have important implications in the diagnosis, management, and monitoring of APLS.
authors.affiliation: Clinical Immunology Unit and Department of Medicine A, Tel Aviv Sourasky Medical Center, University of Tel Aviv, 6 Weizmann Street, Tel Aviv 64239, Israel.
authors.forename: M H
authors.initials: MH
authors.lastname: Wiener
authors.forename: M
authors.initials: M
authors.lastname: Burke
authors.forename: M
authors.initials: M
authors.lastname: Fried
authors.forename: I
authors.initials: I
authors.lastname: Yust
mesh_terms: D000293:Adolescent; D000328:Adult; D000371:Agglutination / Q000276:immunology; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000150:complications / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010974:Platelet Aggregation / Q000276:immunology*; D010979:Platelet Function Tests; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000276:immunology*
chemical_list: D017153:Antibodies, Anticardiolipin