Certain membrane phospholipids are normally prevented from activating the coagulation cascade by binding to circulating phospholipid-binding proteins; antibodies to these phospholipid-binding proteins block this protective attachment and thus predispose to thrombosis.
The antiphospholipid antibody syndrome is an autoimmune disorder that consists of thrombosis and (in pregnancy) fetal demise caused by various antibodies directed against one or more phospholipid-binding proteins (eg, β2-glycoprotein I, prothrombin, annexin). These proteins normally bind to phospholipid membrane constituents and protect them from excessive coagulation activation. The autoantibodies displace the protective proteins and, thus, produce procoagulant endothelial cell surfaces and cause arterial or venous thromboses (see Overview of Thrombotic Disorders). In vitro clotting tests may paradoxically be prolonged because the antiprotein/phospholipid antibodies interfere with coagulation factor assembly and activation on the phospholipid components added to plasma to initiate the tests. The lupus anticoagulant is an antiphospholipid autoantibody that binds to protein/phospholipid complexes. It was initially recognized in patients with SLE, but these patients now account for a minority of people with the autoantibody.
Other symptoms of venous or arterial thrombosis may also develop.
PTT testing is done in patients who are expected to undergo an invasive procedure, in those with unexplained bleeding or clotting, or in those taking certain blood thinners. The lupus anticoagulant is suspected if the PTT is prolonged and does not correct immediately upon 1:1 mixing with normal plasma but does return to normal upon the addition of an excessive quantity of phospholipids (done in the clinical pathology laboratory). Antiphospholipid antibodies in patient plasma are then directly measured by immunoassays of IgG and IgM antibodies that bind to phospholipid/β2-glycoprotein I complexes on microtiter plates.
Heparin, warfarin, and aspirin have been used for prophylaxis and treatment. It is not known whether the newer oral anticoagulants that inhibit either thrombin (dabigatran) or factor Xa (eg, rivaroxaban, apixaban) can be used in place of warfarin for this disorder.
Last full review/revision October 2014 by Joel L. Moake, MD
updates.last-modified October 2014