Antiphospholipid Antibody Syndrome

Central retinal vein occlusion in patient with primary antiphospholipid antibody syndrome.

Signs and Symptoms: Patients with antiphospholipid antibody syndrome (APAS) tend to be under age 50 and female. Up to 2% of women may have antiphospholipid antibodies. Many will also have lupus or other autoimmune diseases.

The most common ocular pathology is thrombosis with resultant ischemia. This manifests as central retinal vein or artery occlusion (CRVO or CRAO), anterior ischemic optic neuropathy (AION), transient ischemic attack (TIA), amaurosis fugax, isolated retinal hemorrhages and cotton wool spots, and retinal neovascularization. While these conditions typically occur in the elderly, APAS patients may experience them earlier in life.

Besides the ocular manifestations, thrombi often affect other systems. Venous thromboses of the arm and leg, sagital, pelvic, mesenteric, portal and axillary vessels, and pulmonary embolism have all been encountered in APAS. With thrombosis in the arterial system, cerebrovascular accidents have also occurred. Thrombocytopenia (reduced platelet count) may also occur in these patients.

An indication of APAS is spontaneous abortion. Preeclampsia and intrauterine growth retardation are associated with APAS.

Pathophysiology: APAS is an autoimmune disorder with two forms. A primary form exists in the absence of clinically or serologically proven autoimmune disease. A secondary form is present in patients with SLE.

In this condition, the body erroneously identifies phospholipids, which are present in cell membranes, as foreign and, consequently, produces antibodies against them. Antiphosphilipid antibodies are a group of circulating antibodies that include anticardiolipin antibody, lupus anticoagulant, and the biologic false-positive test for syphilis.

It's unclear how the antiphospholipid antibodies promote thrombosis. They may inhibit prostacyclin formation with subsequent increased aggregation of platelets, or the antibodies may interfere with the coagulation cascade.

Management: Suspect antiphospholipid antibody syndrome in patients under age 50 with retinal vein occlusion and other thrombotic conditions. Also consider it in unusual thrombotic events such as recurrent or bilateral CRVO. Also suspect patients with a history of thrombotic conditions (retinal vein or artery occlusions, TIA, amaurosis fugax), thrombocytopenia or autoimmune disorders.

Testing includes a complete blood count with differential, PT, PTT, anti-nuclear antibody (ANA), anticardiolipin antibody assay, and dilute Russel viper venom time (DRVVT). The diagnosis of this condition requires positive serology for either the lupus anticoagulant or anticardiolipin antibody (positive anticardiolipin antibody ELISA) on two separate occasions at least eight weeks apart. Beyond the positive serology, there must also be thrombocytopenia, thrombotic disease or recurrent pregnancy loss.

Once APAS is diagnosed, direct your management at the ocular manifestations of APAS. Address APAS to improve outcomes as well as reduce recurrences. Oral anticoagulants such as heparin or low-dose aspirin therapy (81mg) are prescribed. When anti-platelet therapy is insufficient and thrombotic events recur, clinicians add high doses of oral corticosteroids and other immunosuppressants (such as cyclophosphamide).

Clinical Pearls:

• APAS is a relatively newly recognized disorder. Make it part of your differential diagnosis for thrombotic conditions.
• Conditions in which to consider APAS include amaurosis fugax, TIA, retinal hemorrhages and cotton wool spots, central retinal vein and artery occlusion, anterior ischemic optic neuropathy, ophthalmic and cilioretinal artery occlusions.
• Consider APAS in patients under age 50 with central retinal vein and artery occlusion, or any patient with bilateral or recurrent CRVO.
• When suspecting APAS in female patients, inquire about a history of recurrent pregnancy loss.
• Primary APAS exists independently of known autoimmune disease. Through serologic testing and appropriate consultation, you may be the one who diagnoses this autoimmune condition.