Antiphospholipid Antibody Syndrome (APS)

(Anticardiolipin Antibody Syndrome; Lupus Anticoagulant Syndrome)

By Joel L. Moake, MD, Rice University;Baylor College of Medicine

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Thrombotic Disorders
Overview of Thrombotic Disorders
Antiphospholipid Antibody Syndrome (APS)
Antithrombin Deficiency
Hyperhomocysteinemia
Factor V Resistance to Activated Protein C (APC)
Protein C Deficiency
Protein S Deficiency
Protein Z Deficiency
Prothrombin (Factor II) 20210 Gene Mutation

Antiphospholipid antibody syndrome is an autoimmune disorder in which patients have autoantibodies to phospholipid-bound proteins. Venous or arterial thrombi may occur. The pathophysiology is not precisely known. Diagnosis is with blood testing. Anticoagulation is used for prevention and treatment.

The antiphospholipid antibody syndrome (APS) is an autoimmune disorder that consists of thrombosis and (in pregnancy) fetal demise caused by various antibodies directed against one or more phospholipid-bound proteins (eg, beta₂-glycoprotein I, prothrombin, annexin A5). Annexin A5 may bind to phospholipid membrane constituents to prevent the cell membrane from initiating the activation of coagulation. The autoantibodies displace annexin A5 and, thus, produce procoagulant endothelial cell surfaces that can cause arterial or venous thromboses. The mechanism of thrombosis in patients with autoantibodies to phospholipid-bound beta₂-glycoprotein I (apolipoprotein H, a type of cardiolipin) or prothrombin is unknown.

Results of in vitro clotting tests may paradoxically be prolonged because the autoantibodies to phospholipid-bound proteins interfere with coagulation factor assembly and activation on the phospholipid components added to plasma to initiate the tests. The lupus anticoagulant is an autoantibody that binds to phospholipid-bound protein complexes. It was initially recognized in patients with systemic lupus erythematosis (SLE), but these patients now account for only a minority of people with the autoantibody.

Other symptoms of venous or arterial thrombosis may also develop. Patients with autoantibodies to phospholipid-bound prothrombin may have levels of circulating prothrombin that are low enough to increase risk of bleeding.

Diagnosis

Laboratory testing, beginning with PTT

PTT testing is done in patients who are expected to undergo an invasive procedure or in those with unexplained bleeding or clotting. 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/beta₂-glycoprotein I complexes on microtiter plates.

Treatment

Anticoagulation

Heparin, warfarin (except in pregnant women), and aspirin have been used for prophylaxis and treatment.

It is not yet known if the newer oral anticoagulants that inhibit either thrombin (dabigatran) or factor Xa (eg, rivaroxaban, apixaban) can be used in place of heparin or warfarin for this disorder.

Last full review/revision September 2016 by Joel L. Moake, MD