Inhibitors of plasma thromboplastin antecedent (factor XI): studies on mechanism of inhibition.

Acquired inhibitors of plasma thromboplastin antecedent (PTA) have been described in several recent studies, which collectively emphasize the heterogeneity of PTA functions that are impaired by this class of circulating anticoagulants. To clarify whether acquired inhibitors of PTA exhibit inhibitory properties that vary widely from one patient to the next, IgG inhibitors from four patients were isolated. The effect of these inhibitors on the binding of PTA to glass, the activation of kaolin-bound PTA, the coagulant activity of both kaolin-bound and fluid phase activated PTA (aPTA), and the enzymatic activity of aPTA against a low molecular weight substrate was quantified. The relative inhibition of these individual components of PTA activation and function by the four anticoagulants was quite similar. The results indicate that the principal binding sites for acquired inhibitors of PTA are PTA domains involved with surface binding and conversion of PTA to aPTA, with less effective steric impairment of aPTA enzymatic activity.