Acute and chronic effects of a new low molecular weight dermatan sulphate (Desmin 370) on blood coagulation and fibrinolysis in healthy subjects.
The acute and chronic effects on blood coagulation and fibrinolysis of a new molecular weight dermatan sulphate (Desmin 370) have been investigated in a double blind, placebo-controlled cross over study in 12 healthy volunteers. The compound (100 and 200 mg) was injected IM and the expected heparin cofactor II potentiating effect, reflecting dermatan sulphate activity, peaked after 2 h and was still detectable after 9 h. Surprisingly for this type of compound, a substantial increase in anti-Xa activity also appeared and lasted up to 12 h in the absence of a significant change in aPTT. The bovine-thrombin time was not changed, while human-thrombin times were slightly, albeit non-significantly, prolonged. The activity of t-PA was increased 6h after the higher dose, but the overall pattern of fibrinolytic activities did not suggest any important change after drug treatment in comparison to placebo. No residual or cumulative effect on any of the investigated parameters was detectable 24 h after the injection on the 4th and 8th days during repeated daily administration. Parallel in vitro and in vivo investigations showed that the unexpected anti-Xa effect was not attributable to contamination by traces of low molecular weight heparin. Desmin 370, a low molecular weight dermatan sulphate that potentiates heparin cofactor II and also inhibits Factor Xa, deserves clinical evaluation as an antithrombotic agent.
Legnani
C
C
Department of Angiology and Blood Coagulation, University Hospital S. Orsola, Bologna, Italy.
Palareti
G
G
Biagi
R
R
Ludovici
S
S
Maggiore
L
L
Milani
M R
MR
Coccheri
S
S
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D003871:Dermatan Sulfate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D013997:Time Factors
D003871:Dermatan Sulfate