Rapid loss of factor XII and XI activity in ellagic acid-activated normal plasma: role of plasma inhibitors and implications for automated activated partial thromboplastin time recording.

Rapid prolongation of the aPTT of normal plasma upon incubation with ellagic acid containing aPTT reagents was observed. The aPTT prolongation was not due to time-dependent changes in pH in the incubation mixture or loss of activity of the labile coagulation factors VIII and V but occurred as a result of rapid progressive inactivation of ellagic acid-activated factors XII and XI. Prolongation of the aPTT and loss of contact factor activities was not observed in plasma incubated with particulate activator reagents. This finding seemed to indicate that adsorption of factors XII and XI to larger particles during the activation process might protect these factors from inactivation by naturally occurring plasma inhibitors. Evidence is presented which supports previous findings that C1-INH, alpha1-AT, and antithrombin (in the presence of heparin) contribute to factor XIIa and XI a inactivation in ellagic acid-activated plasma and that plasma albumin may compete with factor XII for ellagic acid binding. The data indicate that ellagic acid-containing aPTT reagents have unfavorable properties which seriously limit their usefulness in the clinical laboratory, particularly in respect to recording of the aPTT with certain fully automated clot timers.