Clinical experience with a new antithrombotic (dermatan sulfate) in chronic hemodialysis patients.
Dose finding studies with a new antithrombotic (dermatan sulfate) for the prevention of clot formation in the extracorporeal circuit were performed in chronic hemodialysis patients in comparison with standard heparin treatment. Dermatan sulfate (DS), which inhibits the coagulation via the heparin cofactor II pathway, was given in single predialysis injections, immediately before commencement of the dialysis procedures, in dosages ranging from 2 mg/kg to 6 mg/kg body weight. In our pilot study, an open non comparative study in patients using plate type dialyzers, we observed moderate clot formation in the extracorporeal circuit. In our second study, with a randomized heparin-controlled design in patients with plate type dialyzers, still significant clot formation occurred in the extracorporeal circuit. In the third study, in chronic hemodialysis patients using a cuprophane hollow fiber dialyzer, we also investigated the addition of a small bolus of standard heparin (20 I.U./kg body weight) to the injection of DS. A single bolus injection of 6 mg/kg, with or without the addition of a bolus of standard heparin, had a comparable efficacy as standard heparin treatment. No major bleeding events were encountered in the studies and DS had a reduced effect on the activated partial thromboplastin time as compared to standard heparin. In conclusion, these results suggest that DS in a dose of 6 mg/kg, with or without a small dose of standard heparin, given as single predialysis bolus injections, appears to be an effective alternative to standard heparin and, in addition, it may simplify the anticoagulant administration protocol.
Nurmohamed
M T
MT
Centre for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Amsterdam, The Netherlands.
Knipscheer
H C
HC
Stevens
P
P
Krediet
R T
RT
Roggekamp
M C
MC
Berckmans
R J
RJ
ten Cate
J W
JW
D001777:Blood Coagulation / Q000187:drug effects; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007688:Kidneys, Artificial; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D006435:Renal Dialysis
D005343:Fibrinolytic Agents; D003871:Dermatan Sulfate; D006493:Heparin