Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome

Area of Science:

• Pediatric Nephrology
• Hematology
• Infectious Diseases

Background:

• Hemolytic-uremic syndrome (HUS) is a serious thrombotic complication of Escherichia coli O157:H7 infection.
• The precise timing and causal role of coagulation abnormalities in HUS pathogenesis remain unclear.

Purpose of the Study:

• To investigate whether coagulation cascade activation precedes and potentially causes HUS in children infected with E. coli O157:H7.
• To identify specific markers of coagulation activation and their correlation with renal injury.

Main Methods:

• Measured plasma markers of clotting cascade activation (prothrombin fragment 1+2, t-PA antigen, t-PA-PAI-1 complex, D-dimer) in 53 children with E. coli O157:H7 infection.
• Re-assessed these markers and measured urinary markers of renal injury (beta2-microglobulin, N-acetyl-beta-glucosaminidase) in 16 children who developed HUS.

Main Results:

• Children who developed HUS showed significantly higher plasma levels of prothrombin fragment 1+2, t-PA antigen, t-PA-PAI-1 complex, and D-dimer before azotemia and thrombocytopenia onset.
• Urinary and plasma markers of coagulation activation and fibrinolysis inhibition increased significantly upon HUS development.
• A strong linear correlation was observed between t-PA antigen and t-PA-PAI-1 complex concentrations.

Conclusions:

• Thrombin generation and fibrinolysis inhibition precede renal injury in HUS, suggesting they are the likely cause of kidney damage.
• These findings highlight the critical role of prothrombotic states in the pathophysiology of E. coli O157:H7-associated HUS.