Abstract
During the period of November 2007-January 2008, an increased prevalence of adverse reactions to heparin in hemodialysis patients was noted. These adverse events were attributed to the presence of purposeful contaminant, namely oversulfated chondroitin sulfate (OSCS). The OSCS exhibited a molecular profile similar to heparin (14–16 KDA) and was a weaker anticoagulant (30–40 USP U/mg), however when mixed with heparin it produced super-additive anticoagulant effects. Similar to heparin, the OSCS also produced HIT antibody mediated aggregation of platelets and serotonin release. The contaminated heparin was reportedly used in dialysis globally during the period March 2007–May 2008. Since dialysis patients have been exposed to contaminated heparin, the OSCS may have triggered the generation of anti-heparin platelet factor 4 antibodies (HIT abs). Earlier analysis of dialysis patients plasma obtained in 2006 and 2007, consistently showed a very low prevalence of HIT abs in these patients (5 %). To test the hypothesis that maintenance hemodialysis patients exposed to potentially contaminated heparin may have a greater prevalence of HIT abs, blood from 80 patients on maintenance hemodialysis for the past several weeks, was drawn in June 2008. Plasma samples were analyzed for the presence of HIT abs using a commercially available ELISA kit from GTI (Brookfield, WI). While there was no change in the platelet count, the prevalence of HIT abs in these patients was markedly higher 15/78 (19.2%). Subtyping of the antibody also showed a higher prevalence of IgG subtype in contrast to the previously determined abs which were mainly IgA and IgM. The OSCS was also found to strongly complex with platelet factor 4 and initiate heparin induced platelet aggregation responses. These observations suggest that OSCS contaminant in recalled heparin is capable of triggering a differential immunogenic response in comparison to contaminant free heparin. Regardless of the increased generation of HIT abs no reports on any adverse events and/or thrombocytopenia were apparent from the site where the blood samples were drawn.
The Clinical Significance and Risk Factors of Anti-Platelet Factor 4/heparin Antibody on Maintenance Hemodialysis Patients: A Two-Year Prospective Follow-up