A Protein C Pathway (PCP) Screening Test for the Detection of APC Resistance and Protein C or S Deficiencies

Abstract

A new automated method for screening defects in the Protein C Pathway (PCP) was evaluated. The “PCP test” is based on a phospholipid-rich Russells viper venom reagent, insensitive to heparin and lupus anticoagulants. To minimize interference from other clotting variables, ratios of the clotting time with and without the addition of a protein C activator were usually determined. Plasma samples from healthy volunteers, patients untreated or on oral anticoagulants, patients with factor V Leiden with and without treatment, and patients with protein C and/or S deficiencies were tested. Mixing patient plasmas 1:1 with individual plasmas deficient in factor V, protein C or S was evaluated for identifying the nature of defects by shortening the screening test. The PCP test was found to be sensitive to APC resistance due to factor V Leiden and by mixing with factor V deficient plasma was also useful despite the effects of oral anticoagulants. Results in the group of patients with previous low protein C or S levels suggest that the method has a better sensitivity to protein C than to protein S deficiency. The automated test was simple to use and gave a between-run coefficient of variation below 3% on normal plasmas.

Keywords:

Thrombophilia - protein C pathway - factor V Leiden - protein C - protein S - APC resistance - Russells viper venom test