FURTHER EVIDENCE THAT ACTIVATED PROTEIN-C RESISTANCE CAN BE MISDIAGNOSED AS INHERITED FUNCTIONAL PROTEIN-S DEFICIENCY

A recent report that activated protein C (APC) resistance interferes w ith functional protein S (PS) assays prompted us to re-investigate two pedigrees previously diagnosed as having functional PS deficiency. AP C resistance was demonstrated in all individuals with apparent functio nal PS deficiency. The latter diagnosis was shown to be due to the ass ay being non-linear. functional protein S becoming normal at higher di lutions. This observation, taken in conjunction with results of in vit ro recovery studies with purified PS, leads us to conclude that APC re sistance was the primary disorder in both pedigrees. The misdiagnosis of APC resistance as functional PS deficiency can be prevented by perf orming the PS assay at several dilutions, including concentrations low er than those recommended by PS assay manufacturers. Subjects previous ly diagnosed as having functional PS deficiency should be re-investiga ted for APC resistance.