The intramuscular or
intravenous administration of ISG prepared from human plasma by
ethanol fractionation can elicit such reactions as
pain at the injection site,
flushing, and even
hypotension. Similar adverse reactions to
plasma protein fraction, a volume expander also made by
ethanol fractionation, have been associated with PKA (
Hageman factor fragments) in the product. Twenty-five lots of commercial ISG were therefore analyzed for PKA and
kallikrein, components of the contact activation system which could mediate such reactions through the generation of
kinins in recipients.
Kallikrein activity ranged from undetectable levels to > 60% of the total potential
kallikrein activity in normal plasma. PKA, which was measured by its ability to catalyze the conversion of
prekallikrein to
kallikrein, ranged from 5% to 3950% of the activity in a reference
plasma protein fraction that had caused
hypotension. All but five lots increased vascular permeability in the guinea pig. The five lots which caused no increased were also the lowest in PKA and
kallikrein activity. When ISG ws subjected to gel chromatography to separate the enzymic contaminants from
immunoglobulin G, only the fractions containing PKA and/or
kallikrein increased vascular permeability. Several lots of ISG shortened the nonactivated partial thromboplastin time of normal plasma fro 236 sec to 38 to 55 sec. During gel chromatography, coagulation activity was eluted in a position corresponding to a molecular weight of 150,000; it was inhibited by antibody to human
factor XI. These data indicate that
factor XIa is responsible for the
coagulant activity observed and that PKA and/or
kallikrein are potential mediators of vasoactive reactions to ISG.