Increased plasma thrombomodulin as a vascular endothelial cell marker in patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Several hemostatic and vascular endothelial cell markers were measured in 3 9 patients with thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) and in 20 healthy volunteers to examine the relationship bet ween the occurrence of hemostatic abnormality or vascular endothelial cell injury and patient outcome. The plasma levels of von Willebrand factor, tis sue plasminogen activator (TPA), plasminogen activator inhibitor (PAI-1), a nd the TPA-PAI-1 complex were significantly increased in TTP/HUS patients; however, the levels of these markers were not significantly different betwe en TTP/HUS patients who survived and those who died, suggesting that these markers might not be directly related to outcome. The plasma levels of solu ble granule membrane protein (GMP)-140 were significantly higher in TTP/HUS patients than in healthy volunteers, suggesting that plate lets and vascul ar endothelial cells are activated or injured in TTP/HUS. There was no sign ificant difference in GMP-140 levels between TTP/HUS patients with good and poor prognoses; this may be owing to the release of GMP-140 from platelets . The plasma thrombomodulin (TM) levels in TTP/HUS patients were significan tly higher than in healthy volunteers; the plasma TM levels were significan tly higher in patients who died than in patients who survived. These findin gs showed that TM levels reflect the outcome and that the outcome of TTP/HU S depends on the presence vascular endothelial cell injury. The plasma prot ein C and antithrombin levels were markedly reduced in TTP/HUS patients who died compared with those who survived. These findings suggest that reduced plasma antithrombin and protein C may be useful markers of systemic vascul ar endothelial injury. In conclusion, the results of this study showed that the outcome of TTP/HUS is related to vascular endothelial cell injury and that plasma TM, antithrombin, and protein C levels may be useful markers of systemic vascular endothelial cell injury.