[The role of von Willebrand protease in aetiopathogenesis of thrombotic thrombocytopenic purpura].

Thrombotic thrombocytopenic purpura (TTP) is a disseminated form of thrombotic microangiopathy characterised by thrombocytopenia, microangiopathic haemolysis, a variety of neurologic disturbances, fever and renal dysfunction. Endothelial lesion, activation of apoptosis and factors which induce platelet adhesion and aggregation could play a role in pathogenesis of TTP. Recent studies have demonstrated the inhibiting autoantibody against von Willebrand factor (vWF) cleaving protease in plasma of a great majority of TTP patients. A rare congenital deficiency of protease due to genetic mutations on both alleles has also been described. The accumulation of the ultra-large vWF multimers, due to either congenital or acquired deficiency of protease, exposed to the fluid shear stress in the microcirculation, induces formation of the platelet thrombi thus causing TTP. Cloning and synthesis of the molecular structure of protease raise the prospect for advances in diagnosis and treatment of the disease. Namely, in the absence of the inexpensive, more accurate and commonly available test, a diagnosis is based on the diagnostic dyad: thrombocytopenia and microangiopathic haemolytic anaemia in the absence of other cause. Also, in the absence of the enzyme replacement therapy, a therapeutic plasma exchange remains a gold standard in the treatment of TTP patients. Current assay methods for vWF protease could distinguish TTP from haemolytic uraemic syndrome and other microangiopathic syndromes. All current assays differ in the substrate nature, denaturant, incubation time or the detection method.