Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome.
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 beta2-microglobulin and N-acetyl-beta-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.
Chandler
Wayne L
WL
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle 98105, USA.
Jelacic
Srdjan
S
Boster
Daniel R
DR
Ciol
Marcia A
MA
Williams
Glyn D
GD
Watkins
Sandra L
SL
Igarashi
Takashi
T
Tarr
Phillip I
PI
D000118:Acetylglucosaminidase / Q000652:urine; D015415:Biomarkers / Q000097:blood; D001778:Blood Coagulation Disorders / Q000150:complications*; D001779:Blood Coagulation Factors / Q000032:analysis*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000097:blood; D004927:Escherichia coli Infections / Q000097:blood* / Q000150:complications / Q000652:urine; D019453:Escherichia coli O157; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology*; D006801:Humans; D007223:Infant; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011516:Prothrombin; D018709:Statistics, Nonparametric; D010959:Tissue Plasminogen Activator / Q000097:blood; D001613:beta 2-Microglobulin / Q000652:urine
D015415:Biomarkers; D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D001613:beta 2-Microglobulin; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D000118:Acetylglucosaminidase; D010959:Tissue Plasminogen Activator