An automated chromogenic peptide substrate assay for coagulation factor XII

Area of Science:

• Hematology
• Clinical Chemistry
• Coagulation Diagnostics

Background:

• Factor XII (FXII) plays a role in the intrinsic coagulation pathway.
• Accurate measurement of FXII levels is crucial for diagnosing bleeding and thrombotic disorders.
• Existing FXII assays may be affected by lupus anticoagulants, complicating interpretation.

Purpose of the Study:

• To develop and validate an automated chromogenic peptide substrate assay for factor XII (FXIIcs).
• To compare FXIIcs assay results with conventional clotting (FXIIct) and immunochemical (FXIIag) assays.
• To assess the performance of the FXIIcs assay in blood donors, patients with venous thrombosis, and lupus anticoagulant-positive (LA+) patients.

Main Methods:

• Development of an automated FXIIcs assay on a Cobas Mira S Plus analyzer using a commercial kit.
• Analysis of plasma samples from 320 blood donors, 206 venous thrombosis patients, and 74 LA+ patients.
• Comparative analysis of FXIIcs results against FXIIct and FXIIag assays.

Main Results:

• High correlation (r=0.92) observed between FXIIcs and FXIIct assays in blood donors.
• Low FXII levels detected in a small percentage of blood donors and venous thrombosis patients, all lupus anticoagulant-negative.
• Significant discrepancies between FXIIcs and FXIIct in LA+ patients, with FXIIag results aligning with FXIIcs.

Conclusions:

• The automated FXIIcs assay provides accurate and reliable measurement of factor XII levels.
• The FXIIcs assay is insensitive to lupus anticoagulants, overcoming limitations of FXIIct assays.
• This automated method facilitates routine and accurate FXII level determination in large patient populations.