Antithrombotic properties of dermatan sulphate (MF 701) in haemodialysis for chronic renal failure.
The therapeutic potential of the glycosaminoglycan (GAG), dermatan sulphate (DS), as an antithrombotic agent in humans has yet to be established. We have performed dose ranging studies of DS to determine its effectiveness as an antithrombotic agent in patients (n = 6-8) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients dialysing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg/kg DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efficacy of an i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg kg-1 h-1 and a DS bolus of 5 mg/kg plus an infusion of 1 mg kg-1 h-1 over 5 h, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. Plasma levels of fibrinopeptide A (FPA) and thrombin-antithrombin (TAT) were used as markers of fibrin formation and thrombin generation during dialysis using both membranes. The changes in DS concentration following administration of the different doses were similar in Studies 1 and 2. However, the effectiveness of DS as an anticoagulant appeared to depend markedly on the different dialyser types used in the two studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Ryan
K E
KE
Department of Haematology, Charing Cross and Westminster Hospital, Hammersmith, London, UK.
Lane
D A
DA
Flynn
A
A
Ireland
H
H
Boisclair
M
M
Shepperd
J
J
Curtis
J R
JR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005344:Fibrinopeptide A / Q000378:metabolism; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D006435:Renal Dialysis; D013927:Thrombosis / Q000517:prevention & control
D005343:Fibrinolytic Agents; C046193:antithrombin III-protease complex; D003871:Dermatan Sulfate; D005344:Fibrinopeptide A; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases