Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus

Acquired activated protein C resistance (APCR) has been hypothesized as a p ossible mechanism by which antiphospholipid antibodies (APLAs) cause thromb otic events (TEs). However, available evidence for an association of acquir ed APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APC R is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecu tive, nonselected children with SLE was conducted. Primary clinical outcome s were symptomatic TEs, confirmed by objective radiographic tests. Laborato ry testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was pr esent in 18 (31%) of 58 patients. Acquired APCR was significantly associate d with the presence of LAs but not ACLAs. Acquired APCR was also significan tly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associa ted with the highest risk of a TE. Protein S and protein C concentrations w ere not associated with the presence of APLAs, APCR, or TEs. Presence of ac quired APCR is a marker identifying LA-positive patients at high risk of TE s. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (C) 2001 by The Ameri can Society of Hematology.