The Role of Coagulation and Fibrinolysis in the Pathogenesis of Diarrhea-Associated Hemolytic Uremic Syndrome

 

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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.

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