Treatment of thrombotic microangiopathy

Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenic Purpura (TTP) are syndromes of microangiopathic hemolytic anemia and thrombocytopenia, which have in common thrombotic occlusion of the microvasculature of various organs (thrombotic microangiopathy). In HUS, the lesions are mainly confined to the kidneys and dialysis remains the cornerstone of the treatment until renal function improves. TTP is mostly a disease of adults who often have multiorgan involvement that includes brain, heart, and pancreas. Short-term prognosis is considerably less favorable in adult TTP than it is in children HUS. Despite diverse etiologies, as recently recognized, the underlying pathophysiology is likely to be similar. In recent years it emerged clearly that most cases of HUS are due to an infection with P. coli 0157:H7 that produces two toxins, verotoxin-1 and verotoxin-2, that are toxic to human endothelial cells. It has been suggested that different organ involvement in animals and possibly different manifestations of thrombotic microangiopathy in humans (children versus adults) could be attributed to different organ distribution of verotoxin receptors. Endothelial cell injury, platelet activation, decreased fibrinolytic activity and oxidant injury are then involved in the pathogenesis of the microangiopathic process. Here we overview the treatments available at the moment for thrombotic microangiopathy, with emphasis on possible options based on different clinical presentations. It is concluded that careful supportive management is still the most appropriate form of treatment for classical childhood HUS. Plasma infusion or exchange is effective in adult HUS and acute and chronic/relapsing TTP. The efficacy of corticosteroids is uncertain and probably limited to mild forms of TTP. The role of all the other specific therapies suggested for the treatment of thrombotic microangiopathy still needs to be verified in adequate controlled trials.