Summary
Dermatan sulfate is an antithrombotic glycosaminoglycan which has been shown to be
effective in preventing deep venous thrombosis in general surgery patients when present
at concentrations less than 1 |ig/ml. It has also been found to circulate physiologically
in similar concentrations in pregnant women at term and in cord blood. We investigated
the ability of dermatan sulfate added to plasma at 0.2, 0.5 and 1.0 μg/ml to inhibit
thrombin generation initiated by low concentrations of recombinant human tissue factor
in defibrinated plasma. A dose dependent decrease in thrombin potential was demonstrated
at therapeutically relevant concentrations of dermatan sulfate (0.5 and 1.0 μg/ml)
but there was no induction of a lag phase in thrombin generation. We were unable to
demonstrate a significant effect on thrombin potential of dermatan sulfate at a concentration
similar to that found in pregnancy plasma (0.2 μg/ml). This indicates that either
the dermatan sulfate concentration found in pregnancy plasma is not physiologically
relevant or that our experimental system (which lacks platelets and fibrin) does not
accurately reflect physiologic conditions. The effect on the thrombin potential was
somewhat greater at the lowest concentration of tissue factor and amounted to a maximum
inhibition of approximately 50% at 1 μg/ml dermatan sulfate. A dose dependent increase
in formation of thrombin-heparin cofactor II complexes and a decrease in thrombin-antithrombin
complex formation with increasing dermatan sulfate concentration were observed at
all dermatan sulfate concentrations. Prothrombin consumption was not changed by any
dose of dermatan sulfate. We conclude that dermatan sulfate, at the concentrations
tested, catalyses inhibition of free thrombin by heparin cofactor II but not efficiently
enough to inhibit prothrombinase formation.
