What is the pathophysiology of antiphospholipid syndrome (APS)?

Updated: Sep 30, 2018
  • Author: Suneel Movva, MD; Chief Editor: Herbert S Diamond, MD  more...
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Answer

In APS, the homeostatic regulation of blood coagulation is altered; however, the mechanisms of thrombosis are not yet defined. One hypothesis postulates a defect in cellular apoptosis, which exposes membrane phospholipids to the binding of various plasma proteins, such as beta-2 glycoprotein I. Once bound, a phospholipid-protein complex is formed and a neoepitope is uncovered, which subsequently becomes the target of autoantibodies. Recent evidence suggests that oxidized beta-2 glycoprotein I is able to bind to and activate dendritic cells in a manner similar to activation triggered by Toll-like receptor 4 (TLR-4), which could amplify the production of autoantibodies. [1, 2]

Other proposed mechanisms for the hypercoagulable effect of aPL antibodies, which may or may not depend on beta-2 glycoprotein I, include the following:

  • Production of antibodies against coagulation factors, including prothrombin, protein C, protein S, and annexins

  • Activation of platelets to enhance endothelial adherence

  • Activation of vascular endothelium, which, in turn, facilitates the binding of platelets and monocytes

  • Reaction of antibodies to oxidized low-density lipoprotein, thus predisposing to atherosclerosis and myocardial infarction (MI)


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