Hypotension Associated with Prekallikrein Activator (Hageman-Factor Fragments) in Plasma Protein Fraction

Abstract

Thirteen lots of plasma protein fraction made by one manufacturer were implicated in 23 recent reports of hypotension in surgical patients. Four of these patients required resuscitation after rapid administration of the product in the postoperative period. All implicated lots had prekallikrein-activator activity but low levels of bradykinin and kallikrein. The prekallikrein activator was identified as Hageman-factor fragments by molecular weight (35,000 as estimated by gel chromatography), isoelectric point (4.2 to 4.4), and inhibition by antibody to Hageman factor. These data suggest that Hageman-factor fragments are potent hypotensive agents, presumably because they trigger the generation of bradykinin in recipients. Prekallikrein-activator activity, usually at levels lower than those in the initial 13 implicated lots, was frequently detected in plasma protein fraction made by other manufactures. Several of these lots were associated with additional reports of hypotension. Prekallikrein-activator activity rarely occurred in albumin.

Inhibition of human peptidyl dipeptidase (angiotensin I converting enzyme: kininase II) by human serum albumin and its fragments.

“…The plasma kallikrein-kinin system is believed to be involved in the hypotensive reaction since the preparations are frequently contaminated by bradykinin 26 and by a prekallikrein activator, Hageman factor fragment. 21 Inhibition of CE prolongs the hypotensive effects of kinins and abolishes the vasoconstrictor effect of renin by blocking the release of angiotensin II. 8 '' Bradykinin is inactivated mainly by two enzymes, kininase I and kininase II.…”

“…21 - 26 The presence of kinins, prekallikrein activator and kininase II inhibitors may explain the severe hypotension encountered in some cases after infusion of such preparations, especially when the lung is excluded from the circulation, since the pulmonary vascular bed is very active in cleaving kinins." This study of the inhibition of CE by albumin fragments should help to clarify the nature of complexing of the enzyme by albumin and possibly by other plasma proteins.…”

Surface-mediated defense reactions. The plasma contact activation system.

“…A comprehensive review has appeared (56) of the early studies documenting changes in the contact system in such disorders as the carcinoid (57), postgastrectomy (58), and nephrotic syndromes (59), as well as in type Ila hyperlipoproteinemia (60) and in transfusion reactions (61). The role of surface-mediated defense reactions can be better illustrated by considering the response ofthis system to the challenge of infection, hyperacute allograft rejection, and allergic reactions.…”

Is Albumin Harmful?

“…Albumin can occasionally have other poorly characterized harmful effects, such as hypotension, caused by vasoactive peptides (Alving et al, 1978) or it can cause renal damage (Boesken et al, 1977), but these effects are rare. Some have even suggested that the chemical properties of albumin may be helpful, by improving drug handling or by supplying antioxidants (Quinlan, 1998).…”