Outbreak of adverse reactions associated with contaminated heparin.
BACKGROUND
In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions.


METHODS
Information on clinical manifestations and on exposure was collected for patients who had signs and symptoms that were consistent with an allergic-type reaction after November 1, 2007. Twenty-one dialysis facilities that reported reactions and 23 facilities that reported no reactions were included in a case-control study to identify facility-level risk factors. Unopened heparin vials from facilities that reported reactions were tested for contaminants.


RESULTS
A total of 152 adverse reactions associated with heparin were identified in 113 patients from 13 states from November 19, 2007, through January 31, 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P<0.001). Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin.


CONCLUSIONS
Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause of the outbreak.
Blossom
David B
DB
Epidemic Intelligence Service Program, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Kallen
Alexander J
AJ
Patel
Priti R
PR
Elward
Alexis
A
Robinson
Luke
L
Gao
Ganpan
G
Langer
Robert
R
Perkins
Kiran M
KM
Jaeger
Jennifer L
JL
Kurkjian
Katie M
KM
Jones
Marilyn
M
Schillie
Sarah F
SF
Shehab
Nadine
N
Ketterer
Daniel
D
Venkataraman
Ganesh
G
Kishimoto
Takashi Kei
TK
Shriver
Zachary
Z
McMahon
Ann W
AW
Austen
K Frank
KF
Kozlowski
Steven
S
Srinivasan
Arjun
A
Turabelidze
George
G
Gould
Carolyn V
CV
Arduino
Matthew J
MJ
Sasisekharan
Ram
R
D000925:Anticoagulants / Q000009:adverse effects* / Q000737:chemistry; D016022:Case-Control Studies; D002809:Chondroitin Sulfates / Q000009:adverse effects*; D004196:Disease Outbreaks; D004340:Drug Contamination; D004487:Edema / Q000139:chemically induced / Q000453:epidemiology; D006493:Heparin / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000453:epidemiology; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D006435:Renal Dialysis; D013610:Tachycardia / Q000139:chemically induced / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D014581:Urticaria / Q000139:chemically induced / Q000453:epidemiology
D000925:Anticoagulants; D006493:Heparin; D002809:Chondroitin Sulfates