The anticoagulant effect of heparan sulfate and dermatan sulfate

The potency of the various glycosaminoglycans (GAGs) as anticoagulants in the activated partial thromboplastin time (APTT) test system has been investigated. Heparin, heparan sulfate (HS) and dermatan sulfate (DS) exhibit anticoagulant effect. About 70 times higher concentrations of HS and DS were required to obtain the effect of heparin. The other GAGs, including chondroitin 4-sulfate, chondroitin 6-sulfate, keratan sulfate and hyaluronic acid (HA) did not prolong the APTT at the concentrations used. The influence of the GAGs on thrombin and activated factor X (Xa), and on the inactivation of these clotting enzymes by antithrombin III (At-III) has been studied, using chromogenic substrates for the assay of enzyme activity. All GAGs, except keratan sulfate, had inhibitory effect on the amidolytic activity of thrombin. However, no GAG affected the amidolytic activity of Xa. Heparin and HS accelerate the inactivation of thrombin and Xa by At-III. About 75 times higher concentration of HS was required to obtain the effect of heparin. DS and HA had a slight accelerating effect on the inactivation of thrombin by At-III, but only at a high concentration (500 μg/ml). At concentrations where DS exhibited anticoagulant activity in the APTT test system, no accelerating effect on At-III activity could be detected. Thus, the anticoagulant effect of DS is probably not exerted via At-III, and may in this respect differ from the anticoagulant activity of heparin and HS.