A new screening assay for abnormalities in the Protein C anticoagulant pathway

Abstract number: P0015

Safa O., Smirnow M., Thomas E., Lawson D.

Instrumentation Laboratory, USA

The majority of diagnostic hereditary defects in thrombophilic patients can be linked to Protein C (PC) anticoagulant pathway. Until now, at least three single test (Protein C. Protein S and APC resistance) were used to look for defects in this system. It has long been the goal of coagulation and thrombosis laboratories to have an assay that is specific for screening defects in the PC pathway. Assays developed earlier lacked sensitivity to PS. We introduce a new automatic chromogenic assay for screening and evaluation of the PC pathway. The assay is based on the ability to generate endogenous activated PC (APC) and measure it's effect on thrombin generation by tissue factor pathway, which directly related to the activity of PC/PS system. Thirty-six sample including 8 with PS deficiency, 8 with PC deficiency. 8 APC resistance, and 4 with normal controls were tested with the new assay. Thrombin generation w/wo Protac was quantified by chromogenic activity and expressed as Normalized Ratio; NR = –ptc/+ptc. Four Normal Plasmas had NR = 2.2–2.4, four PS immunodepleted plasmas had NR = 1.1–1.3, four PC immunodepleted plasmas had NR = 1.0–1.2, eight APC resistant plasmas (APC ratio 1.0–1.9) had NR = 1.3–2.0, eight PC deficient plasmas (PC < 60%) had NR 1.3–2.0, eight PS deficient plasmas (PS < 60%) had NR = 1.3–2.0. The result of present evaluation indicated very good sensitivity to PS, PC deficiencies and APC Resistance/FV Leiden. Further clinical studies are required on the patients with thrombosis risk. In conclusion, this assay is very useful for routine screening of patients with thrombosis to identified abnormality in PC anticoagulant pathway.