Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias

Thrombotic thrombocytopenic purpura (TTP) was first described by Moschowitz (1924). The classic pentad of diagnostic features has been recognized for many years. However, several other syndromes are also characterized by similar features. These include haemolytic uraemic syndrome (HUS), eclampsia and the HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). The concept has arisen that they might represent an overlapping spectrum of disease, although with varying pathophysiological features (see Table I). The recent characterization of a novel von Willebrand factor (VWF)-cleaving metalloprotease activity (Furlan et al, 1996; Tsai, 1996) and its deficiency or inhibition in some forms of microangiopathic haemolysis (Furlan et al, 1997, 1998; Tsai & Lian, 1998) has led to speculation that a pathogenic mechanism for individual patients can be defined more readily and appropriate treatment introduced more rapidly. However, there is still considerable confusion, a lack of properly conducted randomized clinical trials and poor co-ordination of clinical data. This is, in part, because these patients present to a range of specialists including haematologists, obstetricians, nephrologists and infectious disease physicians. These guidelines attempt to define the various clinical subtypes, specify the recognized diagnostic features and look critically at management options. It is acknowledged that there is a lack of evidence from well-conducted studies on which to support some of the recommendations made.