The immunobiology and obstetrical consequences of antiphospholipid antibodies.
Two classes of antiphospholipid antibodies (APA) are associated with adverse pregnancy outcomes. Those APA identified by immunoassays using phospholipid-coated surfaces (e.g., anticardiolipin antibodies) seem to bind to the 57 kD anticoagulant protein, beta 2-glycoprotein-I, when complexed with anionic phospholipid bilayers. Such APA may or may not prolong phospholipid-dependent clotting assays. A second class of APA are identified by their interference with phospholipid-dependent clotting assays (i.e., lupus anticoagulants). The latter bind to phospholipids present in a unique hexagonal phase either alone or complexed with prothrombin or beta 2-glycoprotein-I. There is evidence that both classes of APA are directly responsible for adverse pregnancy outcomes including spontaneous abortions, stillbirths, fetal growth retardation, thrombosis, thrombocytopenia, and preeclampsia. Putative APA-mediated pathogenic mechanisms include intervillous thrombosis, intravillous infarctions and decidual vasculopathy. The thrombogenicity of APA may result from their interference with endothelial phospholipids required for antithrombin III and protein C and S anticoagulant activity and prostacyclin synthesis and/or increased endothelial expression of the procoagulants: tissue factor, von Willebrand factor, platelet-activating factor, and plasminogen activator inhibitor type-1. Other prothrombotic properties seem to include: increased platelet aggregation, and reduced beta 2-glycoprotein-1 and annexin V anticoagulant activity. Rigorous diagnostic criteria must be applied to the detection of both classes of APA because the prevention of adverse pregnancy outcomes requires potentially hazardous anticoagulant therapy.
Lockwood
C J
CJ
Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, New York 10029.
Rand
J H
JH
D000818:Animals; D017304:Annexin A5 / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood* / Q000737:chemistry; D001053:Apolipoproteins / Q000378:metabolism*; D001779:Blood Coagulation Factors / Q000032:analysis; D004359:Drug Therapy, Combination; D000939:Epitopes / Q000032:analysis; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007118:Immunoassay / Q000379:methods; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008954:Models, Biological; D008958:Models, Molecular; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D011256:Pregnancy Outcome; D011485:Protein Binding; D011516:Prothrombin / Q000378:metabolism; D053482:beta 2-Glycoprotein I
D017304:Annexin A5; D017152:Antibodies, Antiphospholipid; D001053:Apolipoproteins; D001779:Blood Coagulation Factors; D000939:Epitopes; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D053482:beta 2-Glycoprotein I; D011516:Prothrombin