Activation of coagulation in the childhood haemolytic uraemic syndrome

Renal failure is traumatic at any age, but when it occurs suddenly in childhood, the effects are even more overwhelming. Haemolytic uraemic syndrome (HUS) is the commonest cause of acute renal failure in childhood and is particularly distressing for the child and family. The disease develops within days and makes the child extremely fractious, at the time when daily blood tests are needed, and when he may be immobilized by attachment to a dialysis machine. The disease affects about 150 children a year in Britain and occurs in outbreaks which often generate considerable public interest. The incidence may be increasing, and during 1996 alone there were at least two widely publicised outbreaks. The first, in Japan in 1996 affected nearly 10,000 people and is the largest outbreak yet recorded. The second occurred in Scotland in November 1997, was fatal in eighteen cases, and has been described as the worst outbreak of food poisoning in this country to date. Despite this publicity and considerable research into the disease, the pathogenesis is still incompletely understood and no specific treatment has been shown to be effective. It was the aim of this thesis to shed a little more light on the pathogenesis of this disease by investigating changes in haemostasis.;HUS does in fact cover a group of diseases characterised by a triad consisting of haemolytic anaemia, thrombocytopenia and acute renal dysfunction. Until relatively recently, the heterogeneous nature of the various diseases comprising HUS (see table 1) was not fully appreciated. Furthermore, it is difficult to distinguish between some types of HUS and the closely related syndrome of thrombotic thrombocytopenia purpura (TTP), characterised also by thrombocytopenia and haemolysis but with predominantly neurological rather than renal symptoms. Because of this, the conclusions of many earlier studies of HUS which include a heterogeneous mix of adults and children with a variety of forms of HUS and TTP, comprising different aetiologies, symptoms and prognoses, need to be interpreted with caution.