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Antiphospholipid Antibody Syndrome (APS)

(Anticardiolipin Antibody Syndrome; Lupus Anticoagulant Syndrome)

By

Joel L. Moake

, MD, Baylor College of Medicine

Last full review/revision Jan 2021| Content last modified Jan 2021
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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 by blood tests. Anticoagulation is often used for prevention and treatment.

The antiphospholipid antibody syndrome (APS) is an autoimmune disorder Autoimmune Disorders In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following hypersensitivity reactions may be involved: Type II: Antibody-coated cells... read more that consists of thrombosis and (in pregnancy) fetal demise caused by various antibodies directed against one or more phospholipid-bound proteins (eg, beta-2 glycoprotein 1, prothrombin, annexin A5).

Annexin A5 may bind to phospholipid membrane constituents to prevent the cell membrane from participation in the activation of coagulation. If autoantibodies displace annexin A5, procoagulant endothelial cell surfaces may be exposed and provoke arterial or venous thromboses Overview of Thrombotic Disorders In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more .

The precise mechanism of thrombosis in patients with autoantibodies to phospholipid-bound beta-2 glycoprotein 1 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 erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more Systemic Lupus Erythematosus (SLE) (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. Some patients have thrombocytopenia Overview of Platelet Disorders Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes,... read more Overview of Platelet Disorders .

Catastrophic antiphospholipid antibody syndrome

In a small proportion of patients with APS, widespread thromboses occur in small vessels supplying multiple organs, often including the brain (causing neurologic defects). This syndrome is called catastrophic APS (CAPS) and can be confused with disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more (DIC), heparin-induced thrombocytopenia Heparin-induced thrombocytopenia Platelet destruction can develop because of immunologic causes (viral infection, drugs, connective tissue or lymphoproliferative disorders, blood transfusions) or nonimmunologic causes (sepsis... read more (HIT), and thrombotic microangiopathy (TMA). Its treatment includes high-dose corticosteroids, anticoagulation, plasmapheresis, and sometimes rituximab (an anti-CD20 monoclonal antibody) or eculizumab (an anti-complement component C5 monoclonal antibody).

Diagnosis of Antiphospholipid Antibody Syndrome

  • Laboratory testing, beginning with partial thromboplastin time (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.

Antiphospholipid antibodies in patient plasma are then directly measured by immunoassays of IgG and IgM antibodies that bind to phospholipid/beta-2 glycoprotein 1 complexes.

Treatment of Antiphospholipid Antibody Syndrome

  • Anticoagulation

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

It is possible, but not yet certain, that the direct oral anticoagulant (DOAC) inhibitors Treatment In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more of either thrombin (dabigatran) or factor Xa (eg, rivaroxaban, apixaban) can be used in place of heparin or warfarin for this disorder.

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