Circulating thrombomodulin in thrombotic thrombocytopenic purpura

Abstract

Endothelial cell injury is thought to be one of the causative factors in thrombotic thrombocytopenic purpura (TTP). A novel index of endothelial injury, plasma thrombomodulin, was measured in 13 patients with acute TTP. The mean plasma concentration of thrombomodulin was elevated in patients with TTP (34.23 +/- 19.08 ng/ml) as compared with healthy subjects (16.99 +/- 2.63 ng/ml, P less than 0.001). Eight (61.5%) of 13 patients had high thrombomodulin values. Markedly elevated thrombomodulin levels were observed in TTP patients who had suffered from systemic lupus erythematosus, in whom plasma thrombomodulin was still elevated when they achieved remission. Five of these 13 patients with TTP had normal plasma levels of thrombomodulin. In addition, the plasma thrombomodulin concentrations were correlated well with von Willebrand factor antigen and tissue-type plasminogen activator antigen levels, both of which are released from stimulated or damaged endothelial cells. No difference was found in plasma thrombomodulin levels between patients who achieved remission and who did not. These findings suggest that the magnitude of the endothelial damage in TTP is variable among patients and that plasma thrombomodulin has limited clinical relevance to the severity of TTP.

Serum thrombomodulin

“…Increased sTM levels have recently been demonstrated in patients with thrombotic thrombocytopenic purpura and in a selected group of SLE patients with antiphospholipid antibody syndrome (13)(14)(15). In our investigations of unselected SLE patients in all stages of disease, we found a very close correlation between sTM levels and clinical activity of disease.…”

Thrombomodulin: A marker for endothelial damage during orthotopic liver transplantation

“…,thrombomodulin Ag has been shown to be a marker of endothelial damage in vitro [22] and previous clinical studies have shown that plasma levels of ,thrombomodulin Ag are increased in various diseases associated with endothelial cell damage or proteolytic activity on the endothelial cell surface (DIC [23,24], adult respiratory distress syndrome (ARDS) [24], thromboembolic disease [23,24], thrombotic thrombocytopenic purpura [25,26], diabetes mellitus with microangiopathy [23,27], systemic lupus erythematosus (SLE) [28], and chronic myelogenous leukemia [29]). …”

Identification of functional endothelial protein C receptor in human plasma.

“…These observations, along with the knowledge that soluble thrombomodulin degradation products in plasma are a marker of endothelial damage in various disease states (27,(29)(30)(31)(32)(33)(34), led to the question of whether a soluble circulating form(s) of EPCR existed, and, if so, what role it may have in the protein C pathway.…”

“…Both plasma and urine contain detectable thrombomodulin (27,28), and because the thrombomodulin gene does not contain introns (13), these soluble forms are due to proteolysis of the extracellular domain at the cell surface. Soluble degradation products of thrombomodulin in plasma are known markers of endothelial cell damage in a variety of disease states (27,(29)(30)(31)(32)(33)(34), and are comprised of a mixture of thrombin-binding fragments with varying reduced affinities, as well as nonbinding fragments (27).…”