Can a patient with thrombosis due to Antiphospholipid Antibodies ever have seronegative APS?
Yes. Rarely, patients with large clots will presumably consume the aPL abs into the clot, leading to false-negative results. Consequently, repeating the tests for aPL abs at 12 weeks after the thrombotic event may show they are positive.
Another possibility is that the pathogenic aPL abs are directed against other targets not detected by the aPL ab assays. Such candidate antigens include prothrombin, phosphatidylserine, phosphatidylethanolamine, vimentin–cardiolipin complex, annexin A5, thrombomodulin, protein C, and protein S. Of these, anti-PS/PT antibodies are the most pathogenic. Furthermore, antibodies directed specifically against β2GPI and not picked up by the aCL ELISA assay have been reported to be associated with clots in some individuals particularly when the antibody is directed against domain I-β2GPI. In addition, IgA aPL abs (aCL, anti-β2GPI) should be tested for in patients who are negative for IgG and IgM aPL abs.
Other causes (inherited hypercoagulable states) for thrombosis should always be assessed in patients with negative aPL ab tests. The concept of “seronegative” APS is not recognized unless other causes of thrombosis and antibodies against other candidate antigens are rigorously excluded.