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 hemodialy sis. Various dosages of pentasaccharide, 400-800 nmol/kg, were compare d with a single bolus dose of unfractionated heparin (250 U/kg). The p rimary endpoint in these studies was the duration of dialysis time. In addition, dialyzer filter content, venous trap protein, celite and sa line 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 produce d antithrombotic effects for periods of up to 150+/-42 minutes (n=5). At a lower dosage of 400 nmol/kg pentasaccharide produced weaker effec ts 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 dos age of pentasaccharide; however, at 250 U/kg, a strong effect was note d with unfractionated heparin (> 800 sees, 647+/-211 sees.), respectiv ely. A dose dependent antithrombotic effect was also evident in the st udies on the filter clots and venous trap protein content. No differen ce in the hematocrit was noted in any group. These results clearly sug gest that despite the fact that pentasaccharide does not produce any p rolongation of the coagulation times, it produces a dose dependent ant ithrombotic effect in this model of dog hemodialysis. Furthermore, the se results also suggest that pentasaccharide at an appropriate dosage can be used as an alternate antithrombotic agent during hemodialysis. (C) 1997 Elsevier Science Ltd.