Controversies and unresolved issues in antiphospholipid syndrome pathogenesis and management

While much is understood concerning the clinical features of patients with antiphospholipid syndrome (APS), many issues remain. The proper designation of patients with "definite" APS and the correct categorization of patients by both laboratory and clinical features are matters of ongoing debate. Recent proposals have identified new subsets of patients who have many typical features of APS but either do not fit die criteria for a "definite" diagnosis or have initially negative laboratory tests for antiphospholipid antibodies. Meanwhile, decisions about laboratory tests are based on expert opinion, rather than the results of controlled trials. As for treatment, many guidelines are offered, but few are backed by data from strong clinical trials. This article summarizes the clinical questions remaining to be answered and debates concerning pathogenesis, diagnosis, and management.