Summary
Thrombomodulin (TM) is a cofactor for the thrombin-catalyzed activation of anticoagulant
protein C. However, we have no evidence that thrombomodulin actually activates protein
C during blood coagulation processing, nor do we know whether this activated protein
C acts as an anticoagulant. We studied the inhibitory action of recombinant human
soluble TM (rhs-TM) on thrombin generation in whole plasma. Human plasma was activated
with small amounts of tissue factor using phospholipid vesicles in place of activated
platelets. Thrombin generation was observed. The addition of only 2 nM of rhs-TM prevented
rapid generation of thrombin and reduced the total amount of thrombin generated. In
order to study the influence of the protein C activation pathway on this inhibitory
action of rhs-TM, protein C-depleted plasma was used. rhs-TM had little inhibitory
effect on protein C-depleted plasma. However, the addition of protein C caused a delay
in thrombin generation and a reduction of the maximum thrombin concentration. We concluded
that the anticoagulant activity of rhs-TM was amplified by the protein C activation
pathway.
