Recent insights into antiphospholipid antibody-mediated thrombosis.
The clinically relevant antiphospholipid antibodies (APA) include anticardiolipin antibodies and lupus anticoagulant. Most autoimmune APA require the presence of a cofactor for phospholipid binding, and the growing list of candidate cofactors has prompted redefinition of APA to 'antiphospholipid protein antibodies'. Current evidence favours beta2-glycoprotein I (beta2GPI) and prothrombin as the primary antigens for anticardiolipin antibodies and lupus anticoagulant respectively. Patients with APA show a predisposition for venous and arterial thromboembolism, recurrent fetal loss, thrombocytopenia and a number of neurological syndromes and miscellaneous conditions. The association between APA and thrombosis has been well documented, but a definite mechanism remains to be clarified. Proposed mechanisms have included disruption of endothelial regulatory processes, impairment of fibrinolysis, augmented platelet activation and/or adhesion, inhibition of antithrombin activity and negation of the anticoagulant effects of beta2GPI and annexin V. In this review we describe recent insights into the role of beta2GPI as a natural anticoagulant, the procoagulant effects of APA on the Protein C system, the interactions between APA and prothrombin resulting in augmentation of thrombin generation, and cellular expression of Tissue Factor in patients with APA. Cellular immunity to beta2GPI is also discussed. Elucidation of these pathophysiological mechanisms may shed further light on the association between APA and thrombosis.
Field
S L
SL
UNSW Centre for Thrombosis and Vascular Research, School of Pathology, University of NSW, Sydney, Australia.
Brighton
T A
TA
McNeil
H P
HP
Chesterman
C N
CN
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000009:adverse effects / Q000097:blood* / Q000502:physiology; D000925:Anticoagulants / Q000097:blood / Q000494:pharmacology; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000494:pharmacology; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D008297:Male; D011247:Pregnancy; D011516:Prothrombin / Q000378:metabolism / Q000494:pharmacology; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000276:immunology*; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D053482:beta 2-Glycoprotein I; D011516:Prothrombin