Resistance to activated protein C mimicking dysfunctional protein C: diagnostic approach

It has been reported that resistance to activated protein C interferes with functional plasma-based coagulation assays of protein C, mimicking a type II deficiency. In this study we confirm and extend these findings. In our laboratory approximately 25% of patients with resistance to activated protein C have an apparent type II protein C deficiency. It is important for rapid and accurate diagnosis to be able to confirm or exclude a dysfunction of protein C associated with resistance. We therefore propose a new coagulation assay that requires first adsorption of protein C from plasma, activation with a snake venom and measurement of its anticoagulant activity. This assay is quick, reproducible and can be automated. It is also insensitive to the presence of resistance to activated protein C and allows detection of all types of protein C deficiency. This is important when screening for inherited causes of thrombophilia since more than one defect might be present and interference from resistance to activated protein C is common.