PLASMA VON-WILLEBRAND-FACTOR ANTIGEN (VWF-AG) AND THROMBOMODULIN (TM)LEVELS IN ADULT THROMBOTIC THROMBOCYTOPENIC PURPURA HEMOLYTIC-UREMIC SYNDROMES (TTP HUS) AND BONE-MARROW TRANSPLANT-ASSOCIATED THROMBOTIC MICROANGIOPATHY (BMT-TM)/

Endothelial damage is thought to be a contributing factor in the patho genesis of Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndro mes (TTP/HUS). The present studies measured two markers of endothelial cell stimulation and/or activation [von Willebrand Factor (vWF:Ag) an d thrombomodulin (TM)] in patients with TTP/HUS disorders and compared them to controls. The patient groups consisted of adults with TTP/HUS , with (n = 13) and without (n = 14) peak Cr levels >2.0 mg/dl. Additi onally, 52 patients with Bone Marrow Transplant-associated Thrombotic Microangiopathy (BMT-TM) following allogeneic BMT were evaluated. Both vWF:Ag and TM were elevated in all patient groups compared to control s. TTP/HUS patients with peak Cr >2.0 mg/dl had higher TM levels (P < 0.001) than did those with peak Cr levels below 2 mg/dl. However, thro mbomodulin/creatinine (TM/Cr) ratios did not differ in these two group s nor did they differ from controls. BMT-TM pts had higher vWF:Ag leve ls and higher TM/Cr ratios than controls and TTP/HUS, P < 0.001. The m edian TM/Cr ratio in BMT-TM was 91 (range = 34-229) compared to 38 (ra nge = 29-50) in controls, P < 0.001 and 38(range = 6 to 156) in TTP/HU S, P < 0.001. Additionally both TM (P < 0.001) and TM/Cr (P < 0.02) we re higher in patients with Grades 3 and 4 BMT-TM compared to those wit h Grade 2 BMT-TIW. These results suggest that endothelial cell activat ion occurs in TTP/HUS and BMT-TM. Since TM/Cr ratios were higher in BM T-TM compared to TTP/HUS, these findings suggest that the mechanism of elevated TM in BMT-TM cannot be explained solely by altered renal exc retion. Taken together, these findings strongly indicate a role of end othelial cell damage in BMT-TM. (C) 1996 Wiley-Liss, Inc.