ABSTRACT
The hemolytic-uremic syndrome (HUS) is a frequent cause of acute renal failure in
childhood. It comprises acute acquired hemolysis, thrombocytopenia, and renal dysfunction.
Very many disease processes can lead to this constellation, the most frequent one
in childhood being an infection by bacteria that produce Shiga toxin or Shiga-like
toxins (SLTs) . In industrialized countries, the first identified human pathogen to
cause HUS was Escherichia coli O157H7, and this organism remains the most common one. The mechanisms by which these
bacteria cause hemorrhagic colitis and HUS are incompletely understood. The bacteria
are able to adhere to the mucosa of the colon. The local and systemic effects that
follow the intestinal invasion are responsible for the bloody diarrhea. In a further
step, the SLTs reach the blood stream and attach to the endothelium of the small arterioles
mainly in the kidney but also in other organs. The endothelial cells express a toxin-specific
receptor that enables the contact between toxin and cells. Damage to the endothelium
causes platelet aggregation and activation, which trigger fibrin deposition. Although
thrombotic changes in the microcirculation have been recognized in many histological
studies, it is only recently that coagulation studies have been able to demonstrate
clearly localized intravascular coagulation. The finding that the fibrinolytic system
is inhibited in HUS has been challenged. By using specific and sensitive tests to
measure the active moiety of plasminogen activator inhibitor type 1 (PAI-1) and comparing
the findings in HUS patients and appropriate controls, it has become clear that in
diarrhea-associated HUS the fibrinolytic system is rather stimulated. In this contribution
the pathophysiology of diarrhea-associated HUS is discussed with special emphasis
on coagulation and fibrinolysis.
KEYWORD
Hemolytic-uremic syndrome - diarrhea-associated hemolytic-uremic syndrome in childhood
- coagulation - fibrinolysis
