Clinical Pearls & Morning Reports
Published May 23, 2018
The antiphospholipid syndrome is a systemic autoimmune disease defined by thrombotic or obstetrical events that occur in patients with persistent antiphospholipid antibodies. It is often associated with other systemic autoimmune diseases such as systemic lupus erythematosus (SLE). Read the latest Review Article here.
Q: Are patients with antiphospholipid antibodies always symptomatic?
A: Patients who are positive for antiphospholipid antibodies may present with no related symptoms. Such patients are usually identified during an evaluation for systemic autoimmune diseases, early miscarriages, an elevated activated partial-thromboplastin time (aPTT), or a false positive result of a syphilis test.
Q: Is the diagnosis of the antiphospholipid syndrome established when antiphospholipid antibodies are identified?
A: The diagnosis of the antiphospholipid syndrome requires positive antiphospholipid-antibody tests; however, not every positive test has diagnostic importance. The diagnosis should be considered in patients with persistent, moderate-to-high-risk antiphospholipid-antibody profiles (tested with validated methods) and in patients with any antiphospholipid-antibody–related finding.
A: Stroke and transient ischemic attack are the most common arterial events in patients with the antiphospholipid syndrome. Patients with venous thromboembolism most commonly present with lower-extremity deep-vein thrombosis, pulmonary embolism, or both. Antiphospholipid-antibody–related complications of pregnancy generally develop after 10 weeks of gestation; losses before 10 weeks, especially if not recurrent, would more commonly be attributed to chromosomal defects. Antiphospholipid-antibody positivity should be included in the differential diagnosis if a patient presents with thrombosis at a young age, with an unusual site of or recurrent thrombosis, with late pregnancy loss, with early or severe preeclampsia, or with the HELLP syndrome (characterized by hemolysis, elevated liver-enzyme levels, and low platelet counts). When combined with thrombosis or obstetrical complications, the following clinical findings may be a clue that a patient has the antiphospholipid syndrome: livedo, signs or symptoms of another systemic autoimmune disease, unexplained prolongation of the aPTT, or mild thrombocytopenia. Severe thrombocytopenia (platelet count, <20,000 per cubic millimeter) is rare and should prompt the clinician to consider other causes of a low platelet count.
A: The use of low-dose aspirin for primary thrombosis prevention is controversial, given the low quality of evidence and lack of prospective data documenting that this strategy is effective. For patients with the antiphospholipid syndrome defined by venous thrombosis, initial therapy with unfractionated or low-molecular-weight heparin, followed by long-term anticoagulant therapy with a vitamin K antagonist such as warfarin (target international normalized ratio [INR], 2 to 3), is recommended. For most patients with persistent antiphospholipid antibodies and otherwise unprovoked venous thromboembolism, discontinuation of anticoagulant therapy would be associated with an unacceptably high risk of recurrent thrombosis. However, the benefit of prolonged anticoagulation is less certain in patients who are positive for antiphospholipid antibodies and in whom thrombosis was provoked — for example, by a surgical procedure — and in patients with laboratory tests for antiphospholipid antibodies that become negative over time. Recurrent venous thrombosis despite warfarin use is a well-recognized complication of the antiphospholipid syndrome. There is no high-quality evidence to support any particular management strategy when warfarin therapy fails despite a therapeutic INR, but options include higher-intensity warfarin therapy (target INR, 3 to 4); the addition of low-dose aspirin, hydroxychloroquine, or a statin; use of a different anticoagulant, such as low-molecular-weight heparin; and a combination of these approaches.