Acquired
activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which
antiphospholipid antibodies (APLAs) cause thrombotic events (
TEs). However, available evidence for an association of acquired 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) APCR 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 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic
TEs, confirmed by objective radiographic tests. Laboratory 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 present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with
TEs. There was significant interaction between APCR and LAs in the association with
TEs. Presence of both APCR and LAs was associated with the highest risk of a TE.
Protein S and
protein C concentrations were not associated with the presence of APLAs, APCR, or
TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of
TEs. Acquired APCR may reflect interference of LAs with the
protein C pathway that may represent a mechanism of LA-associated
TEs. (Blood. 2001;97:844-849)