The effects of glycosaminoglycans on coagulation: a thromboelastographic study.
Endogenous heparinoids impair coagulation, evidenced by thrombelastography in cirrhotic patients with bacterial infection, but it is not clear which glycosaminoglycans can be detected by native and heparinase-modified thrombelastography. To assess the effects of different glycosaminoglycans on thrombelastography parameters and the reversibility of these effects by heparinase-I-modified thrombelastography. Twenty volunteers were enrolled. Solutions of heparan sulphate, dermatan sulphate, and chondroitin-4-sulphate were prepared at 'equivalent' concentrations, based on the composition and anticoagulant activity of danaparoid. Serial dilutions of each glycosaminoglycan were prepared to achieve 1.0, 0.5, 0.1, and 0.05 U/ml. Native and heparinase-modified thrombelastography, anti-activated factor X activity and heparin cofactor II activity were evaluated at each concentration. A statistically significant heparin-like effect was seen with 1 and 0.5 U/ml heparan sulphate, and 1 and 0.5 U/ml dermatan sulphate, which was completely reversed by heparinase-modified thrombelastography. Anti-activated factor X activity was significantly increased in samples containing heparan and dermatan sulphates. The heparin cofactor II activity decreased with 1.0 and 0.5 U/ml dermatan sulphate and chondroitin-4-sulphate, but not with heparan sulphate. Heparan and dermatan sulphates affect haemostasis when added to whole blood in vitro, detectable by native thrombelastography and completely reversed by heparinase-I-modified thrombelastography. They may therefore be responsible for the heparin-like effect seen by thrombelastography in patients with cirrhosis and bacterial infection.
Senzolo
M
M
Liver Transplantation and Hepatobiliary Unit, Royal Free Hospital, London, UK.
Coppell
J
J
Cholongitas
E
E
Riddell
A
A
Triantos
C K
CK
Perry
D
D
Burroughs
A K
AK
D001424:Bacterial Infections / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000494:pharmacology; D005355:Fibrosis / Q000097:blood; D006025:Glycosaminoglycans / Q000494:pharmacology*; D015844:Heparin Cofactor II / Q000494:pharmacology; D019763:Heparin Lyase / Q000494:pharmacology; D006801:Humans; D013916:Thrombelastography / Q000379:methods*
D006025:Glycosaminoglycans; D003871:Dermatan Sulfate; D015844:Heparin Cofactor II; D002809:Chondroitin Sulfates; D019763:Heparin Lyase