Laboratory monitoring of pentasaccharide in a dog model of hemodialysis.
Varying dosages of pentasaccharide (400-800 nmol/kg) were compared to a 250-U/kg single bolus dosage of unfractionated heparin (UFH) in a dog model of hemodialysis. Several laboratory assays were used to monitor the effects of pentasaccharide and UFH. The pentasaccharide did not produce any anticoagulant effects as measured by the activated partial thromboplastin time. However, in the anti-Xa chromogenic assay and the Heptest assays, there was a dose-dependent prolongation after pentasaccharide administration. In the group of dogs administered 800 nmol/kg of pentasaccharide, there was a 50% decrease in the thrombin antithrombin (TAT) complex level after 60 minutes on dialysis. In the UFH-treated dogs, wide variations in assays were observed. There was a marked elevation in the activated partial thromboplastin time and Heptest assays up to 6 hours after UFH administration. Both anti-Xa and anti-IIa activity was measured up to 4 hours. In the TAT assay, UFH was found to have a stronger effect in suppressing the formation of TAT in comparison to the pentasaccharide. These results suggest that pentasaccharide can be used as a replacement for UFH in a dog model of hemodialysis to keep the dialysis circuit patent. In addition, the anti-Xa-based assays such as the Heptest and the chromogenic anti-Xa assays can be used to monitor the effects of pentasaccharide in this model.
Hoppensteadt
D A
DA
Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA. dhoppen@wpo.it.luc.edu
Jeske
W P
WP
Walenga
J M
JM
Fu
K
K
Yang
L H
LH
Ing
T S
TS
Herbert
J M
JM
Fareed
J
J
D000818:Animals; D019411:Clinical Laboratory Techniques; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008954:Models, Biological; D008991:Monitoring, Physiologic; D009844:Oligosaccharides / Q000627:therapeutic use*; D006435:Renal Dialysis
D005343:Fibrinolytic Agents; D009844:Oligosaccharides; C064764:PENTA