Comparative Studies On Heparin Contaminant Interactions with Normals, Liver Disease, Heparin Treated and Oral Anticoagulant Treated Patients Plasma.

Abstract 2093

Poster Board II-70

Heparin, a conventionally used anticoagulant, manufactured during the period of November 2007 to April 2008 was recalled by the United States Food and Drug Administration due to severe adverse complications and deaths. Further investigations revealed that heparin was contaminated with oversulfated chondroitin sulfate (OSCS). Most of the coagulation factors are produced in the liver and acute or chronic hepatocellular failure may cause significant decrease in the vitamin K-dependent coagulation factors such as Factors II, VII, IX and X and also protein C and protein S. It is important to study the effects of OSCS in patients treated with coumadin, heparin and in patients with liver disease. It was hypothesized that OSCS causes synergistic interactions with coumadin, heparin and may cause adverse effects when administered in patients with liver disease. In order to validate this hypothesis OSCS from different sources such as Bovine OSCS, Shark OSCS and Porcine OSCS were supplemented in plasma samples obtained from coumadinized, heparinized and liver diseased patients. Each of these agents was supplemented in these sets of plasma samples at a final concentration of 2.5ug/ml. Saline was also supplemented in these plasma samples which served as control. These different OSCS were also supplemented in the plasma samples obtained from normal healthy volunteers. Global clotting assays such as prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) 5Units/ml were performed. Significant prolongation of the PT, APTT and TT 5U/ml when compared to saline control, was observed in icteric plasma samples and a slight prolongation in coumadinized and heparinized plasma samples was observed (as depicted in the following table).

These results suggest that OSCS from various sources produced marked augmentation of the anticoagulant responses in plasma samples collected from patients treated with oral anticoagulants and heparin. Most notably the heparin components produced a relatively stronger anticoagulant effect in the plasma samples in liver disease patients. It is also interesting to note that the individual contaminants in shark and porcine OSCS produced its own assay dependent effects which were most pronounced in the liver disease patients. These results strongly suggest that the heparin contaminant may augment the anticoagulant and bleeding effects in patients with anticoagulant and hypocoagulable states.