Pathophysiology and treatment of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS).

The central pathogenic feature of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is the formation of platelet aggregates, perhaps by damaged endothelial cells. The evidence for endothelial cell damage has been supported by multiple findings, including the harmful effects of TTP/HUS plasma, which induces endothelial cell apoptosis. Ultra-large multimers of von Willebrand factor (vWf), which activates platelets, are found in TTP/HUS patients, presumably after being released into circulation from damaged endothelial cells. It has been reported that loss or dysfunction of the vWf-cleaving protease is related to the development of acute or chronic TTP/HUS. Detection of platelet activation in TTP/HUS patients, which previously had been difficult, is now possible with a particle-counting technique using light scattering. TTP/HUS occurring after bone marrow transplantation (BMT), similar to that in classic TTP/HUS, appears to represent a separate facet of the disease. We observed that BMT-TTP/HUS might be predicted at an early stage by determining any increase in plasma interleukin-12 at the time of leukocyte recovery. It is known that plasma treatment is effective for TTP/HUS patients; we found that a high-molecular-weight fraction (HMW-F) of plasma is effective in treating chronic TTP/HUS patients. HMW-F of plasma may contain the main factor necessary for improvement of TTP/HUS syndrome.