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Molecular and functional heterogeneity in contaminants isolated from recalled heparin. Impact on anticoagulation and potential adverse reactions
Abstract number: PP-WE-143
Fareed1 J., Hoppensteadt1 D., Jeske2 W., Adiguzel1 C., Iqbal1 O., Walenga2 J.
11Pathology 22Cardiovascular Institute, Loyola University Medical Center, Maywood, IL, USA
How-to-cite Fareed J, Hoppensteadt D, Jeske W, Adiguzel C, Iqbal O, Walenga J. Molecular and functional heterogeneity in contaminants isolated from recalled heparin. Impact on anticoagulation and potential adverse reactions. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract PP-WE-143
The primary contaminant in recalled batches of unfractionated heparin (UFH) is reported to be oversulfated chondroitin sulfate (OSCS). It has been assumed that different heparin batches contained similar forms of OSCS. Non-heparin contaminants were isolated from four batches of contaminated UFH and two batches of LMWH by digestion of heparin followed by alcohol precipitation and ion-exchange chromatography. Anticoagulant activities were measured using whole blood and plasmatic assays. Thrombin generation inhibition and protamine/PF4 neutralization studies were carried out in human plasma. Each contaminant's interaction with AT and HCII was characterized. The contaminated UFHs did not exhibit major differences in molecular weight profile (14.8–15.6 kDa), USP potency or anticoagulant actions. There were differences in their anti-Xa:anti-IIa ratios (0.93–1.24) and in the amount of heparinase resistant material (14–30%). Two heparins also contained high molecular dermatan sulfate (30–40 kDa). Each isolated contaminant exhibited distinct neutralization profiles with PF4 and protamine. The LMWHs were comparable in molecular weight and biologic actions, but differed in heparinase-1 digestion profile. The molecular weight of the contaminant isolated from LMWH was lower (12.8 vs. 14.1–16.8 kDa). The contaminants isolated from LMWHs also exhibited differences in thrombin generation inhibition. The contaminants isolated from heparin and LMWH had potencies of 28–46 USP U/mg and 38–46 USP U/mg, respectively. These studies indicate that contaminants isolated from recalled batches of heparin are heterogenous. Moreover, the contaminants obtained form LMWHs may exhibit additional structural and biologic differences. The variations observed in the adverse reactions with recalled heparins may be due to compositional variations in the contaminants.
Disclosure of interest: none declared.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
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