Pain and cyanosis associated with alpha 1-proteinase inhibitor.
OBJECTIVE
The purpose of this study was to investigate adverse reaction reports of pain and/or cyanosis attributed to alpha 1-proteinase inhibitor (A1PI), a plasma alpha-globulin protein used to treat A1PI deficiency.


METHODS
The Food and Drug Administration's (FDA) Spontaneous Reporting System for the collection and analysis of suspected adverse reactions to drugs and biologics was searched for all reports with dates from January 1, 1988, through October 31, 1989, in which A1PI was named as the suspect biologic. A case of pain and/or cyanosis was defined and characteristics of cases were compared with all other reactions. Information about the production of A1PI and results from animal studies conducted by the manufacturer were also gathered.


RESULTS
Fourteen cases of acute chest pain, back pain, and/or cyanosis among patients receiving A1PI infusions were reported to the FDA. The clinical aspects of reported cases were consistent with a rapidly acting, nonallergic mechanism and were easily distinguished from other reactions associated with A1PI. The characteristics of reported cases, the epidemic curve, and lot-specific analyses suggested a point source and strongly implicated two A1PI lots. Information about the production of A1PI and results from animal studies further implicated high-molecular-weight polysaccharides associated with sucrose stabilization of the suspect lots.


CONCLUSIONS
These cases resemble adverse reactions attributed to complexes of protamine and heparin (a mucopolysaccharide). Similar vasoactive mechanisms are suggested. Research is needed to further define the pathophysiology associated with polysaccharide moieties.
Clark
J A
JA
Office of Epidemiology and Biostatistics, Food and Drug Administration, Rockville, Maryland 20857.
Gross
T P
TP
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D001416:Back Pain / Q000139:chemically induced* / Q000453:epidemiology; D001681:Biological Assay; D002637:Chest Pain / Q000139:chemically induced* / Q000453:epidemiology; D002851:Chromatography, High Pressure Liquid; D003490:Cyanosis / Q000139:chemically induced* / Q000453:epidemiology; D004340:Drug Contamination / Q000706:statistics & numerical data; D004345:Drug Industry; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D011134:Polysaccharides / Q000009:adverse effects / Q000032:analysis; D012621:Seasons; D000515:alpha 1-Antitrypsin / Q000009:adverse effects* / Q000600:supply & distribution
D011134:Polysaccharides; D000515:alpha 1-Antitrypsin