Von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157: H7-associated hemolytic uremic syndrome

H. M. Tsai, W. L. Chandler, R. Sarode, R. Hoffman, S. Jelacic, R. L. Habeeb, S. L. Watkins, C. S. Wong, G. D. Williams, P. I. Tarr

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Abstract

Hemolytic uremic syndrome (HUS) usually occurs after infection with Shiga toxin-producing bacteria. Thrombotic thrombocytopenic purpura, a disorder with similar clinical manifestations, is associated with deficient activity of a circulating metalloprotease that cleaves von Willebrand factor at the Tyr842-Met843 peptide bond in a shear stress-dependent manner. We analyzed von Willebrand factor-cleaving metalloprotease activity and the status of von Willebrand factor in 16 children who developed HUS after Escherichia coli O157:H7 infection and in 29 infected children who did not develop this complication. Von Willebrand factor-cleaving metalloprotease activity was normal in all subjects, but von Willebrand factor size was decreased in the plasma of each of 16 patients with HUS. The decrease in circulating von Willebrand factor size correlated with the severity of thrombocytopenia and was proportional to an increase in von Willebrand factor proteolytic fragments in plasma. Immunohistochemical studies of the kidneys in four additional patients who died of HUS demonstrated glomerular thrombi in three patients, and arterial and arteriolar thrombi in one patient. The glomerular thrombi contained fibrin but little or no von Willebrand factor. A decrease in large von Willebrand factor multimers, presumably caused by enhanced proteolysis from abnormal shear stress in the microcirculation, is common in HUS.

Original languageEnglish (US)
Pages (from-to)653-659
Number of pages7
JournalPediatric Research
Volume49
Issue number5
StatePublished - 2001

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Hemolytic-Uremic Syndrome
Escherichia coli O157
von Willebrand Factor
Metalloproteases
Thrombosis
Shiga Toxin
Thrombotic Thrombocytopenic Purpura
Microcirculation
Infection
Fibrin
Thrombocytopenia
Proteolysis
Bacteria
Kidney
Peptides

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157 : H7-associated hemolytic uremic syndrome. / Tsai, H. M.; Chandler, W. L.; Sarode, R.; Hoffman, R.; Jelacic, S.; Habeeb, R. L.; Watkins, S. L.; Wong, C. S.; Williams, G. D.; Tarr, P. I.

In: Pediatric Research, Vol. 49, No. 5, 2001, p. 653-659.

Research output: Contribution to journalArticle

Tsai, HM, Chandler, WL, Sarode, R, Hoffman, R, Jelacic, S, Habeeb, RL, Watkins, SL, Wong, CS, Williams, GD & Tarr, PI 2001, 'Von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157: H7-associated hemolytic uremic syndrome', Pediatric Research, vol. 49, no. 5, pp. 653-659.
Tsai, H. M. ; Chandler, W. L. ; Sarode, R. ; Hoffman, R. ; Jelacic, S. ; Habeeb, R. L. ; Watkins, S. L. ; Wong, C. S. ; Williams, G. D. ; Tarr, P. I. / Von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157 : H7-associated hemolytic uremic syndrome. In: Pediatric Research. 2001 ; Vol. 49, No. 5. pp. 653-659.
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AU - Chandler, W. L.

AU - Sarode, R.

AU - Hoffman, R.

AU - Jelacic, S.

AU - Habeeb, R. L.

AU - Watkins, S. L.

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AU - Tarr, P. I.

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