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Antiphospholipid Syndrome (APS)

(Anticardiolipin Antibody Syndrome; Lupus Anticoagulant Syndrome)


Michael B. Streiff

, MD, Johns Hopkins University School of Medicine

Reviewed/Revised Aug 2023

Antiphospholipid syndrome is an autoimmune disorder characterized by venous and arterial thrombosis or pregnancy complications (eg, recurrent miscarriage) and persistent autoantibodies to phospholipid-bound proteins. The pathophysiology is not precisely known. Diagnosis is by blood tests. Anticoagulation is often used for prevention and treatment.

The antiphospholipid syndrome (APS) is an autoimmune disorder Autoimmune Disorders In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following types of hypersensitivity reactions may be involved: Type II: Antibody-coated... read more that is characterized by arterial, venous, or microvascular thrombosis or recurrent pregnancy loss caused by antibodies directed against one or more phospholipid-bound proteins (eg, beta-2 glycoprotein 1, prothrombin, annexin A5). In the clinical laboratory, antiphospholipid syndrome is associated with anticardiolipin antibodies, beta-2 glycoprotein 1 antibodies, and the lupus anticoagulant (or lupus inhibitor) which causes prolongation of phospholipid-dependent coagulation assays such as the PTT or dilute Russell viper venom time (dRVVT). The antibodies that cause prolongation of coagulation tests were originally called lupus anticoagulants because they were initially identified in patients with systemic lupus erythematosus (SLE). However, this terminology is no longer used because these antibodies can also occur in patients without SLE (as occurs in primary APS).

The pathogenesis of thrombosis in APS is unclear. Beta-2 glycoprotein 1 in plasma binds to phospholipid-rich surfaces. Antibodies to beta-2 glycoprotein 1 upregulate cellular adhesion proteins, such as E selectin, and procoagulant proteins, such as tissue factor. Tissue factor is a receptor and cofactor for factor VII and is expressed on epithelial cells to help form a hemostatic barrier. In addition, antibodies to beta-2 glycoprotein 1 downregulate expression of tissue factor pathway inhibitor, an endogenous anticoagulant protein. Antiphospholipid antibodies also activate neutrophils and monocytes, which activate tissue factor, as well as platelets and complement. Each of these derangements may contribute to the hypercoagulable state associated with antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome

The diagnosis of CAPS should be considered in patients with multiorgan failure (dysfunction of three or more organs) who have positive laboratory test results for APS. Acute kidney injury, encephalopathy, adrenal hemorrhage (due to thrombosis), skin necrosis, and diffuse alveolar hemorrhage Diffuse Alveolar Hemorrhage Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage that originates from the lung parenchyma (ie, the alveoli) as opposed to the airways. There are numerous causes, but... read more Diffuse Alveolar Hemorrhage are known manifestations.

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 Syndrome

  • Laboratory testing, beginning with partial thromboplastin time (PTT) and the dilute Russell viper venom time (DRVVT)

In patients with clinical events (thrombosis or pregnancy loss) that suggest APS, laboratory testing should be done to confirm the diagnosis.

In the presence of antiphospholipid antibodies, the PTT is prolonged and does not correct with 1:1 or 4:1 mixing with normal plasma. Correction of the PTT after adding excess purified phospholipids is consistent with the presence of an antiphospholipid antibody.

The dilute Russell viper venom time (DRVVT) is another assay to detect the lupus inhibitor. It is more sensitive than the PTT to the presence of antiphospholipid antibodies. The venom causes coagulation by activating factor X. The presence of lupus anticoagulant prolongs the clotting process. Normal plasma has no effect on the clotting time, but addition of excess phospholipid reverses the prolongation.

Immunoassays for IgG and IgM antibodies against cardiolipin and beta-2 glycoprotein 1 are also done. It is important to do both immunoassays and coagulation assays when diagnosing APS because some patients will only have positive results for one test.

To confirm the diagnosis, the positive tests should be repeated 12 weeks after initial testing to confirm abnormal results.

Treatment of Antiphospholipid Syndrome

  • Anticoagulation

In patients with thrombotic APS, indefinite treatment with warfarin is the standard approach (1 Treatment reference Antiphospholipid syndrome is an autoimmune disorder characterized by venous and arterial thrombosis or pregnancy complications (eg, recurrent miscarriage) and persistent autoantibodies to phospholipid-bound... read more ). Higher rates of recurrent thromboembolism with DOACs have been noted, so these medications should not be used for treatment of thrombotic APS.

Unfractionated heparin or low molecular weight heparin plus low-dose aspirin is used during pregnancy to prevent recurrent pregnancy losses in women with APS. After delivery, unfractionated heparin or low molecular weight heparin is continued for 6 weeks for thromboprophylaxis.

Treatment reference

  • 1. Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018;378(21):2010-2021. doi:10.1056/NEJMra1705454

Drugs Mentioned In This Article

Drug Name Select Trade
Hepflush-10 , Hep-Lock, Hep-Lock U/P, Monoject Prefill Advanced Heparin Lock Flush, SASH Normal Saline and Heparin
RIABNI, Rituxan, RUXIENCE, truxima
Coumadin, Jantoven
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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