A chromogenic assay for activated protein C resistance

Area of Science:

• Hematology
• Molecular Biology
• Clinical Diagnostics

Background:

• Activated protein C (APC) resistance is a significant cause of inherited thrombophilia.
• A common genetic factor is the Arg506Gln point mutation in factor V, impairing APC-mediated inactivation.
• Current diagnostic methods, like the activated partial thromboplastin time (aPTT) assay, have limitations.

Purpose of the Study:

• To develop and validate a novel chromogenic assay for diagnosing APC resistance.
• To overcome the limitations of existing aPTT-based diagnostic methods.

Main Methods:

• A chromogenic assay was developed measuring APC's capacity to limit factor Xa generation.
• The assay assesses the ratio of factor Xa activity with and without APC.
• Results were compared with aPTT assay findings and validated in patient cohorts.

Main Results:

• The chromogenic assay demonstrated a clear distinction between normal individuals and those with APC resistance.
• APC response ratios correlated well with aPTT assay results.
• The assay identified 23/24 individuals with the Arg506Gln mutation and factor V deficiency.

Conclusions:

• The developed chromogenic assay is a reliable diagnostic tool for APC resistance.
• This assay provides a valuable alternative to aPTT-based methods for identifying thrombophilia risk.
• Further studies can explore its clinical utility in diverse patient populations.