Development of new heparin-like compounds and other antithrombotic drugs and their interaction with vascular endothelial cells

The anticlotting and antithrombotic activities of heparin, heparan sulfate, low molecular weight heparins, heparin and heparin-like compounds from var ious sources used in clinical practice or under development are briefly rev iewed. Heparin isolated from shrimp mimics the pharmacological activities o f low molecular weight heparins. A heparan sulfate from Artemia franciscana and a dermatan sulfate from tuna fish show a potent heparin cofactor II ac tivity. A heparan sulfate derived from bovine pancreas has a potent antithr ombotic activity in an arterial and venous thrombosis model with a negligib le activity upon the serine proteases of the coagulation cascade. It is sug gested that the antithrombotic activity of heparin and other antithrombotic agents is due at least in part to their action on endothelial cells stimul ating the synthesis of an antithrombotic heparan sulfate.