Hypotensive reaction during staphylococcal protein A column therapy in a patient with anomalous degradation of bradykinin and Des-Arg9-bradykinin after contact activation.
BACKGROUND
Hypotensive reactions have occurred in patients taking angiotensin converting enzyme (ACE) inhibitors after infusion of blood previously in contact with negatively charged surfaces capable of generating kinins, which accumulate when ACE, a kininase, is inhibited. A patient with anomalous bradykinin (BK) metabolism who experienced hypotension during extracorporeal staphylococcal protein A (SPA) therapy while on an ACE inhibitor was studied.


METHODS
A patient with mitomycin-associated hemolytic-uremic syndrome received SPA treatments after her ACE inhibitor, lisinopril, was held. Lisinopril was restarted before her 18th SPA treatment, and immediately after return of treated plasma she developed facial redness and hypotension, which resolved after the return stopped and recurred when restarted. To study formation and degradation of kinins, exposed her plasma to glass beads. We found a normal kinin formation rate but an abnormal degradation and accumulation of Des-Arg9-BK. The kinin degradation enzymes ACE, aminopeptidase P (APP), and carboxypeptidase N (CPN) were measured while on an ACE inhibitor, showing absence of ACE activity, low APP, but normal CPN.


CONCLUSIONS
This patient's vasodilation and hypotension during SPA therapy was associated with a pre- existing anomaly of BK metabolism. Her ACE inhibitor shifted degradation toward Des-Arg9-BK formation, and her low APP was associated with a prolonged t50 and accumulation of the vasoactive Des-Arg9-BK.
Molinaro
Giuseppe
G
Faculty of Pharmacy, Department of Mathematics and Statistics, University of Montreal, Montréal, Canada.
Adam
Albert
A
Lepage
Yves
Y
Hammerschmidt
Dale
D
Koenigbauer
Ulrike
U
Eastlund
Ted
T
D000208:Acute Disease; D000626:Aminopeptidases / Q000097:blood / Q000172:deficiency*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001249:Asthma / Q000150:complications; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000097:blood*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005483:Flushing / Q000139:chemically induced; D005898:Glass; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000150:complications; D007022:Hypotension / Q000139:chemically induced*; D007163:Immunosorbent Techniques; D007890:Leiomyosarcoma / Q000188:drug therapy / Q000556:secondary; D017706:Lisinopril / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008666:Metalloendopeptidases / Q000097:blood; D008863:Microspheres; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D013205:Staphylococcal Protein A; D055672:Static Electricity; D014594:Uterine Neoplasms / Q000188:drug therapy; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D013205:Staphylococcal Protein A; C024626:bradykinin, des-Arg(9)-; D016685:Mitomycin; D004317:Doxorubicin; D017706:Lisinopril; D000626:Aminopeptidases; D008666:Metalloendopeptidases; D001920:Bradykinin