Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome

Wayne L. Chandler, Srdjan Jelacic, Daniel R. Boster, Marcia A. Ciol, Glyn D. Williams, Sandra L. Watkins, Takashi Igarashi, Phillip I. Tarr

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Abstract

Background: The hemolytic-uremic syndrome is a thrombotic complication of Escherichia coli O157:H7 infection. It is not known whether the coagulation abnormalities precede, and potentially cause, this disorder. Methods: In 53 children infected with E. coli O157:H7, we measured a panel of markers indicating activation of the clotting cascade and renal function within four days after the onset of illness. These markers were measured again in as many as possible of the 16 children in whom the hemolytic-uremic syndrome developed. Results: The children in whom the hemolytic-uremic syndrome subsequently developed had significantly higher median plasma concentrations of prothrombin fragment 1+2, tissue plasminogen activator (t-PA) antigen, t-PA-plasminogen-activator inhibitor type 1 (PAI-1) complex, and D-dimer than children with uncomplicated infection. These abnormalities preceded the development of azotemia and thrombocytopenia. When the hemolytic-uremic syndrome developed, the urinary concentrations of beta 2-microglobulin and N-acetyl-Β-glucosaminidase rose significantly (P=0.03 for both increases); the plasma concentrations of t-PA antigen, t-PA-PAI-1 complex, D-dimer, and plasmin-antiplasmin complex also increased significantly. The concentration of t-PA antigen correlated with that of the t-PA-PAI-1 complex in a linear regression model (squared correlation coefficient, 0.80; P< 0.001). Conclusions: In the hemolytic-uremic syndrome, thrombin generation (probably due to accelerated thrombogenesis) and inhibition of fibrinolysis precede renal injury and may be the cause of such injury.

Original languageEnglish
Pages (from-to)23-32
Number of pages10
JournalNew England Journal of Medicine
Volume346
Issue number1
DOIs
StatePublished - Jan 3 2002

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    Chandler, W. L., Jelacic, S., Boster, D. R., Ciol, M. A., Williams, G. D., Watkins, S. L., Igarashi, T., & Tarr, P. I. (2002). Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. New England Journal of Medicine, 346(1), 23-32. https://doi.org/10.1056/NEJMoa011033