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Better Recognition of Antiphospholipid Syndrome Needed

Antiphospholipid syndrome (APS), a systemic autoimmune disease, can be underrecognized, according to a recently published review in the New England Journal of Medicine (2018;378(21):2010-2021). Experts say more patient and physician education is needed for this disease that can cause blood clots and pregnancy complications, and other problems such as low platelet counts, anemia, kidney disease, and heart valve disease; these problems can occur in patients with or without other systemic autoimmune diseases such as lupus.

"We need to increase the recognition of APS among general physicians," said Doruk Erkan, MD, MPH, a rheumatologist at the Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, in New York City, an APS expert, and a coauthor of the article. "We need physicians to think about the disease in their differential diagnosis, first, and second, make the correct diagnosis as the interpretation of the blood tests can be tricky."

Patients who are positive for antiphospholipid antibodies (aPL) may present with no related symptoms and are usually identified during an evaluation for systemic autoimmune diseases, low platelet counts, recurrent miscarriages, an elevated activated partial-thromboplastin time (a test commonly ordered before surgeries to determine the bleeding risk), or a false-positive screening result of a syphilis test. Symptomatic patients seek medical attention for blood clots pregnancy complications, or other clinical problems as a consequence of aPL. Stroke and transient ischemic attack are the most common arterial events in patients with APS. Patients with venous events most commonly present with lower-extremity deep vein thrombosis (DVT), pulmonary embolism, or both. Antiphospholipid-antibody-related complications of pregnancy generally develop after 10 weeks of gestation, which include miscarriages or intrauterine growth restriction.

The NEJM article was coauthored by David Garcia, MD, Associate Medical Director of Anti-Thrombotic Therapy at the University of Washington School of Medicine, Seattle. "Antiphospholipid antibodies are not only a diagnostic marker for APS, but also a risk factor for blood clots and pregnancy complications, which are commonly multifactorial,” said Dr. Garcia. “For instance, the risk of blood clots is magnified when there are multiple risk factors, such as the combination of birth control pill use and the presence of antiphospholipid antibodies."

"A common complaint heard from patients with APS is that doctors did not diagnose their disease in a timely fashion or their doctors do not understand their disease. A typical example is a young woman with platelet counts that are slightly low and miscarriages; however, aPL tests are not ordered until they present with stroke," said Dr. Erkan. "Another example is a young patient that comes in with DVT with no other blood clot risk factors, and aPL is not considered as part of the diagnostic work-up."

In addition to the underrecognition of APS, overdiagnosis is another concern, as not every positive aPL test is clinically significant," said Dr. Erkan. Although aPL are detected in 10 percent to 15 percent of the general population with blood clots or pregnancy problems, clinicians should consider both the aPL test profile and additional blood clotting risk factors in evaluating aPL-positive patients.

Tests to detect aPLs include the lupus anticoagulant (LA) test, anticardiolipin antibody (aCL) enzyme-linked immunosorbent assay (ELISA), and anti-β2-glycoprotein-I (aβ2GPI ) ELISA. The NEJM article provides guidance for clinicians about the interpretation of these aPL tests, including how to assess the individual aPL tests and aPL profile. For instance, transient low-level aPL-positivity is common during infections, which is not clinically important, whereas persistent moderate-to-high titers of aCL and aβ2GPI correlate better with aPL-related clinical events.  

"We hope that our APS review article published in a high-impact journal will help increase the recognition of APS worldwide," said Dr. Erkan, who is also the co-chair of the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION). APS Action is a collaborative effort to prevent, treat, and cure aPL-associated clinical manifestations through high-quality, multicenter, and multidisciplinary clinical research.

Hospital for Special Surgery in the United States is one of the major referral centers for APS, and also the lead coordinating center for APS ACTION (www.apsaction.org).

The article can be found at https://www.nejm.org/doi/full/10.1056/NEJMra1705454.