Efficacy of pentasaccharide in a dog model of hemodialysis.
A synthetic heparin pentasaccharide with sole anti-Xa actions has been evaluated for its antithrombotic efficacy in a dog model of hemodialysis. Various dosages of pentasaccharide, 400-800 nmol/kg, were compared with a single bolus dose of unfractionated heparin (250 U/kg). The primary endpoint in these studies was the duration of dialysis time. In addition, dialyzer filter content, venous trap protein, celite and saline ACT and hematocrit measurement. Pentasaccharide at dosages of 600 and 800 nmol/kg produced an extension of dialysis time (> 180 minutes) in contrast to unfractionated heparin at 250 U/kg which only produced antithrombotic effects for periods of up to 150 +/- 42 minutes (n = 5). At a lower dosage of 400 nmol/kg pentasaccharide produced weaker effects and the dialysis circuit was patent for periods of 122 +/- 14.8 (n = 5) minutes. The saline and celite ACT times were not extended at any dosage of pentasaccharide; however, at 250 U/kg, a strong effect was noted with unfractionated heparin (> 800 secs, 647 +/- 211 secs.), respectively. A dose dependent antithrombotic effect was also evident in the studies on the filter clots and venous trap protein content. No difference in the hematocrit was noted in any group. These results clearly suggest that despite the fact that pentasaccharide does not produce any prolongation of the coagulation times, it produces a dose dependent antithrombotic effect in this model of dog hemodialysis. Furthermore, these results also suggest that pentasaccharide at an appropriate dosage can be used as an alternate antithrombotic agent during hemodialysis.
Hoppensteadt
D A
DA
Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA.
Jeske
W P
WP
Walenga
J M
JM
Fu
K
K
Yang
L H
LH
Ing
T
T
Herbert
J M
JM
Fareed
J
J
D000818:Animals; D001798:Blood Proteins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006400:Hematocrit; D006493:Heparin / Q000008:administration & dosage; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000138:chemical synthesis; D006435:Renal Dialysis; D013997:Time Factors; D014914:Whole Blood Coagulation Time
D001798:Blood Proteins; D005343:Fibrinolytic Agents; D009844:Oligosaccharides; C064764:PENTA; D006493:Heparin