Individualized anticoagulation with dermatan sulphate for haemodialysis in chronic renal failure.
BACKGROUND
Dermatan sulphate (DS) is a selective thrombin inhibitor with antithrombotic properties and low bleeding potential. In preliminary studies it was reported to be effective for preventing clot formation in the haemodialysis circuit.


METHODS
Ten patients on maintenance haemodialysis for chronic renal failure underwent three consecutive investigation phases. In phase 1 (individual dose titration), repeated dialyses were performed with increasing doses of DS until successful dialysis was obtained in two sessions at the same dose. In phase 2, individualized DS doses were validated by a randomized crossover comparison with the individual heparin dose of each patient. In phase 3, each patient underwent 24 consecutive dialyses with DS over 8 weeks. Successful dialysis was defined as completion of the procedure without visible clot formation in the bubble traps and lines or a greater than 20% decrease in dialyser capacity. Dialysis efficiency (decrease in serum urea and creatinine, Kt/V), APTT prolongation, bleeding time, and DS plasma concentrations were also assessed.


RESULTS
Phase 1: successful dialysis was achieved in nine patients with 4 mg/kg DS as a predialysis intravenous bolus followed by continuous infusion of 0.65 mg/kg/h. One patient required 5 mg/kg plus 1.3 mg/kg/h. Phase 2: no statistically significant differences were found between DS and heparin in any of the investigated variables. Residual dialyser capacity and dialysis efficiency indexes indicated equivalent efficacy. Phase 3: residual dialyser capacity and dialysis efficiency did not change with time. There was no accumulation of DS in plasma. No bleeding or thrombocytopenia were observed.


CONCLUSIONS
The dose of DS can be individually titrated to suppress clot formation during haemodialysis as efficiently as with individualized heparin. Such an individualized DS regimen maintains its anticoagulant efficacy and is safe in prolonged use.
Boccardo
P
P
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Melacini
D
D
Rota
S
S
Mecca
G
G
Boletta
A
A
Casiraghi
F
F
Gianese
F
F
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D006435:Renal Dialysis / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology
D000925:Anticoagulants; D003871:Dermatan Sulfate