Effects of glycosaminoglycans on factor XI activation by thrombin

The recent observation that coagulation factor XI is activated by the serine protease thrombin indicates that factor XI may play a role in sustaining the haemostatic process by activating factor IX, after coagulation has been initiated by the factor VIIa/tissue factor catalytic complex. Since negatively charged substances, such as dextran sulphate or sulphatides, have been shown to enhance the activation of factor XI by thrombin, we investigated the effect of glycosaminoglycans on this reaction. A 60-fold enhancement in activation was observed in the presence of heparin and more modest increases were seen with dermatan sulphate and chondroitin sulphates A and C. The increase in activation was greater if Zn2+ was included in the reactions with glycosaminoglycans. The combination of heparin or chondroitin sulphate C and Zn2+ supported factor XI autoactivation in addition to factor XI activation by thrombin; an effect noted previously only with dextran sulphate.