Outbreak of Adverse Reactions Associated with Contaminated Heparin

Abstract

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.

Does the Heparin Lock Concentration Affect Hemodialysis Catheter Patency?

“…On the basis of these observations, a recent position paper recommended that a 1000 units/ml heparin solution be adopted as the standard concentration for locking hemodialysis catheters (10). Finally, recent contamination problems associated with the manufacturing process have substantially increased the cost of heparin (11).…”

Unique heparan sulfate from shrimp heads exhibits a strong inhibitory effect on infections by dengue virus and Japanese encephalitis virus

“…Furthermore, in 2008, some pharmaceutical Hep preparations were found to be contaminated with artificial oversulfated chondroitin sulfate and associated with anaphylactoid-type reactions [7][8][9][10]. This led to a shortage of 5 pharmaceutical Hep and much public concern.…”

Identification of Chemically Sulfated/desulfated Glycosaminoglycans in Contaminated Heparins and Development of a Simple Assay for the Detection of Most Contaminants in Heparin

“…1 Contaminated heparin was linked to at least 149 deaths 2 and hundreds of adverse reactions in the US and Germany in 2007 and 2008. 3 The contaminants in heparin were reported as an impurity, specifically dermatan sulfate, and a contaminant, chemically oversulfated chondroitin sulfate (OSCS), presumed to derive from animal cartilage chondroitin sulfate based on NMR analysis. 4 Heparin is prepared from crude heparin that is usually isolated from porcine intestine or bovine lung entrails.…”