title: 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).
abstract: Endothelial damage is thought to be a contributing factor in the pathogenesis of Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS). The present studies measured two markers of endothelial cell stimulation and/or activation [von Willebrand Factor (vWF:Ag) and 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. Additionally, 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 controls. 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, thrombomodulin/ creatinine (TM/Cr) ratios did not differ in these two groups nor did they differ from controls. BMT-TM pts had higher vWF:Ag levels and higher TM/Cr ratios than controls and TTP/ HUS, P < 0.001. The median TM/Cr ratio in BMT-TM was 91 (range = 34-229) compared to 38 (range = 29-50) in controls, P < 0.001 and 38 (range = 6 to 156) in TTP/HUS, P < 0.001. Additionally both TM (P < 0.001) and TM/Cr (P < 0.02) were higher in patients with Grades 3 and 4 BMT-TM compared to those with Grade 2 BMT-TM. These results suggest that endothelial cell activation occurs in TTP/HUS and BMT-TM. Since TM/Cr ratios were higher in BMT-TM compared to TTP/HUS, these findings suggest that the mechanism of elevated TM in BMT-TM cannot be explained solely by altered renal excretion. Taken together, these findings strongly indicate a role of endothelial cell damage in BMT-TM.
authors.affiliation: Special Hematology Laboratory, Western Pennsylvania Cancer Institute, Western Pennsylvania Hospital, Pittsburgh 15224, USA.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Zeigler
authors.forename: C S
authors.initials: CS
authors.lastname: Rosenfeld
authors.forename: D F
authors.initials: DF
authors.lastname: Andrews
authors.forename: J
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: J M
authors.initials: JM
authors.lastname: Raymond
authors.forename: R K
authors.initials: RK
authors.lastname: Shadduck
authors.forename: R E
authors.initials: RE
authors.lastname: Kramer
authors.forename: J F
authors.initials: JF
authors.lastname: Gryn
authors.forename: P B
authors.initials: PB
authors.lastname: Rintels
authors.forename: E C
authors.initials: EC
authors.lastname: Besa
authors.forename: J N
authors.initials: JN
authors.lastname: George
mesh_terms: D000328:Adult; D015415:Biomarkers; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology*; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008833:Microcirculation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000473:pathology; D018180:Thrombomodulin / Q000032:analysis*; D019172:Transplantation Conditioning / Q000009:adverse effects; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D018180:Thrombomodulin; D014841:von Willebrand Factor; D003404:Creatinine