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Kidney Int. 1998 Oct;54(4):1324-30.

Activation of both coagulation and fibrinolysis in childhood hemolytic uremic syndrome.

Author information

  • 1Department of Pediatrics, Center for Molecular and Vascular Biology, University Hospital Gasthuisberg, Leuven, Belgium. Christel.VanGeet@uz.kuleuven.ac.be

Abstract

BACKGROUND:

Thrombotic microangiopathy is the fundamental lesion in diarrhea-associated hemolytic uremic syndrome. The extent of the lesion in the renal parenchyma determines the severity and outcome of the disorder, bilateral renal cortical necrosis being the worst end of the spectrum. In the early years, intravascular coagulation was considered the most important pathogenic mechanism. Yet, individual coagulation factors were normal in the vast majority of patients and therapy with anticoagulants did not alter the course. Recent studies indicate that impaired fibrinolysis might be of importance.

METHODS:

We studied seven variables of the coagulation pathway (PT, aPTT, fibrinogen, FVIII:c, von Willebrand factor, thrombin-antithrombin complexes, prothrombin fragments 1+2) and seven parameters of the fibrinolytic system (plasminogen, alpha2-antiplasmin, C1-esterase inhibitor, tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor type 1, D-dimer) in 24 pediatric patients with diarrhea-associated hemolytic uremic syndrome and in 15 children with acute renal failure not due to hemolytic uremic syndrome. Samples were collected at diagnosis and every second day thereafter for a period of ten days. Additional samples were collected from patients who underwent dialysis, that is, before and after each session from those subjected to hemodialysis and every day from those subjected to peritoneal dialysis. The obtained data were compared with data from a control group consisting of healthy children.

RESULTS:

Our data show four important features. (1) A significant increase in both thrombin-antithrombin complexes (P < 0.005) and prothrombin fragments 1 + 2 (P < 0.001) is observed in hemolytic uremic patients as compared to patients with acute renal failure of other causes. This finding is clearly indicative for an activation of the coagulation pathway. (2) Patients with the hemolytic uremic syndrome have significantly higher D-dimer levels, a sensitive marker of fibrin-specific fibrinolysis, as compared to patients with acute renal failure of other causes (P < 0.005). (3) Levels of plasminogen activator inhibitor-1 (active antigen as well as plasminogen activator inhibitor-1 activity) are not different in both patient groups. In contrast, plasma levels of tissue-type plasminogen activator and urokinase-type plasminogen activator are significantly higher in the hemolytic uremic patients than in those with acute renal failure of other causes (P < 0.01 and P < 0.05 respectively). (4) Hemodialysis leads to an increase in tissue-type plasminogen activator antigen and a decrease of plasminogen activator inhibitor-1 activity levels.

CONCLUSIONS:

Our data demonstrate that in children with diarrhea-associated hemolytic uremic syndrome, limited intravascular coagulation occurs, without evidence of impaired fibrinolysis.

PMID:
9767551
[PubMed - indexed for MEDLINE]
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