Anomaly of the des-Arg9-bradykinin metabolism associated with severe hypotensive reactions during blood transfusions: a preliminary study.
BACKGROUND
Severe hypotensive reactions have been described after the transfusion of platelets or red cells through negatively-charged bedside white cell-reduction filters. The possibility of a role for bradykinin (BK) in the genesis of these reactions has been raised.


METHODS
To understand if an anomaly of BK metabolism is associated with these reactions, the metabolism of BK and des-Arg9-BK was studied in the sera of four patients who presented with a severe hypotensive transfusion reaction. Tests were performed in the absence and the presence of complete in vitro inhibition of angiotensin-converting enzyme (ACE) activity by enalaprilat.


RESULTS
In the presence of ACE inhibition (enalaprilat), the half-life (t1/2) of BK measured in the sera of patients who presented with a severe hypotensive transfusion reaction (361 +/- 90 sec) was not significantly different from that measured in the sera of normal controls (249 +/- 16 sec). In the presence of ACE inhibition (enalaprilat), the t1/2 of des-Arg9-BK was significantly greater in patients who presented with a severe hypotensive transfusion reaction (1549 +/- 319 sec) than in normal controls (661 +/- 38 sec) (p < 0.001).


CONCLUSIONS
A metabolic anomaly mainly affecting the degradation of des-Arg9-BK could be responsible for its accumulation in vivo. Des-Arg9-BK could be responsible, at least in part, for severe hypotensive transfusion reactions.
Cyr
M
M
School of Pharmacy, University of Montréal, Québec, Canada.
Hume
H A
HA
Champagne
M
M
Sweeney
J D
JD
Blais
C
C
Gervais
N
N
Adam
A
A
D000293:Adolescent; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000097:blood; D015773:Enalaprilat / Q000494:pharmacology; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D005260:Female; D006207:Half-Life; D006801:Humans; D007022:Hypotension / Q000097:blood* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D017713:Platelet Transfusion / Q000009:adverse effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; C024626:bradykinin, des-Arg(9)-; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D001920:Bradykinin