A new treatment for TTP?
摘要
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that mainly affects adult patients. It is characterized by microangiopathic haemolytic anaemia, thrombocytopenia, neurological disturbances and renal failure [ 1 ]. These symptoms are related to the presence of von Willebrand factor (VWF)-rich platelet thrombi in the arterioles and capillaries. The VWF, a multimeric plasma glycoprotein secreted mainly by endothelial cells, is crucial for both platelet adhesion and aggregation, especially at the high shear rates in the microvasculature. The VWF is secreted in the form of high molecular weight multimers with a high potency to aggregate platelets. Thus, the size of VWF multimers is physiologically regulated in vivo by a specific metalloprotease, The ADAMTS13 ( A D esintegrin A nd M etalloprotease with a T hrombo S pondin-like domain), that cleaves the largest multimers in order to prevent the spontaneous formation of platelet thrombi in the microcirculation. The absence of ADAMTS13 activity in the plasma leads to the persistence of high molecular weight VWF multimers with ensuing platelet aggregation and thrombotic microangiopathy. The ADAMTS13 may be deficient in rare cases due to a mutation in the corresponding gene (Upshaw–Schulman syndrome) or, more frequently, to circulating, mostly inhibitory auto-antibodies (Abs) directed against ADAMTS13. In 33% to 90% of cases, idiopathic TTP is related to a severe functional deficiency of ADAMTS13 in plasma due to circulating (Abs) to ADAMTS13 [ 2 ]. Plasma therapy including both plasma infusion and plasma exchange (PE) has dramatically improved TTP prognosis, decreasing the mortality rate from 90% to less than 20% [ 3 ]. However, a subset of patients with acquired TTP requires very long-term plasma therapy to prevent fatal outcome and to achieve a sustained remission. In these patients, complementary treatments including immunosuppressive agents (corticosteroids, vincristine, cyclophosphamide, azathiopri