Obstetric Antiphospholipid Syndrome: Has the Black Swan Swallowed a Red Herring?

Several years after the first description of the antiphospholipid syndrome (APS) in 19831, Nigel Harris warned that, although they do exist, patients with APS are as rare as black swans — and predicted that “the value of studying antiphospholipid antibodies (aPL) [might] easily be lost in a sea of overinterpreted and over-reported laboratory and clinical findings2.” Twenty-seven years later, the Obstetric Task Force of the 14th International Congress on Antiphospholipid Antibodies has confirmed the continuing lack of evidence supporting an association between aPL and recurrent early miscarriage (REM)3. They noted the absence of consistent, predictable clinical outcomes from therapeutic trials and suggested potential causes. Despite apparent adherence to the 1999 initial Sapporo4 and 2006 revised Sydney5 criteria, studies have used heterogeneous patient selection protocols, variable laboratory inclusion criteria, and small sample sizes. In addition, there has been a lack of pathological or genetic evaluation to determine the nature of pregnancy losses when they occurred. The Task Force expressed concern regarding what they termed the “considerable enthusiasm” for “diagnosing APS and treating as yet unrecognized obstetric morbidities in the setting of positive aPL results.” Given the absence of critical studies of association and therapeutic benefit, they felt that such diagnostic fervor would serve only to further obscure the search for genuine associations and proven treatments. After 30 years of APS investigations, it would be reasonable to expect increased understanding of the obstetric complications related to aPL, but unfortunately, despite or perhaps because of the “considerable enthusiasm” noted above, there is less clarity, particularly with regard to how or even whether REM fits into the puzzle3,6,7,8. At the Treatment and Evaluation of Recurrent Miscarriage (TERM) program in Toronto, we have been involved in therapeutic and observational … Address correspondence to Dr. C.A. Clark, Suite 1800, 655 Bay St., Toronto, Ontario, Canada M5G2K4; E-mail: cclarksolo{at}aol.com

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