Defective Esterase and Kinin-Forming Activity in Human Fletcher Trait Plasma

Abstract

Fletcher trait plasma failed to generate kinin and developed only a small amount of arginine esterase activity at an abnormally slow rate following surface activation. Neither defect was due to a deficiency of Hageman factor (HF, factor XII) or kininogen or to an excessively rapid inactivation of evolving kinin. Pyrex pretreated with Fletcher trait plasma did not generate kinin normally in fresh normal plasma. Fractions rich in prekallikrein prepared from normal, HF-deficient, or plasma thromboplastin antecedent (PTA)-deficient plasma developed kallikrein activity by direct activation during incubation with trypsin or HF fragments formed by digesting partially purified HF with trypsin. In contrast, identical fractions of Fletcher trait plasma did not develop this activity. Although this finding suggested that Fletcher trait plasma was deficient in prekallikrein, materials eluted from Celite that had been incubated in Fletcher trait plasma contained both esterase and kinin-generating activities. Celite eluates prepared from normal and Fletcher trait plasma released kinin from partially purified kininogen equally well. This release was blocked by soybean trypsin inhibitor but not by lima-bean trypsin inhibitor. Therefore, although unfractionated Fletcher trait plasma appears to be functionally and antigenically deficient in normal prekallikrein, it may actually contain a different prekallikrein which is activated by exposure to Celite but not by exposure to activated HF or trypsin.