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 o
f pentasaccharide and UFH, The pentasaccharide did not produce any anticoag
ulant effects as measured by the activated partial thromboplastin time. How
ever, in the anti-Xa chromogenic assay and the Heptest assays, there was a
dose-dependent prolongation after pentasaccharide administration. In the gr
oup of dogs administered 800 nmol/kg of pentasaccharide, there was a 50% de
crease 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 an
d anti-IIa activity was measured up to 4 hours. In the TAT assay, UFH was f
ound to have a stronger effect in suppressing the formation of TAT in compa
rison to the pentasaccharide. These results suggest that pentasaccharide ca
n be used as a replacement for UFH in a dog model of hemodialysis to keep t
he dialysis circuit patent. In addition, the anti-Xa-based assays such as t
he Heptest and the chromogenic anti-Xa assays can be used to monitor the ef
fects of pentasaccharide in this model. (C) 1999 Elsevier Science Ltd. All
rights reserved.