Thrombotic thromboytopenic purpura: another example of immunomediated thrombosis.
Much progress has been made in recent years in understanding the mechanisms of TTP, through the demonstration of the role of ultra-large von Willebrand factor multimers and of ADAMTS13 deficiency in the pathogenesis of immune-mediated and genetic forms. There are, however, cases of TTP with normal or only slightly reduced levels of ADAMTS13, that may be due to the inhibition of the VWF cleaving activity ofADAMTS13 under the flow conditions of the microcirculation. The laboratory methods for assayingADAMTS13 are currently too complex to be used routinely on a large scale. In addition, they fail to reflect the conditions of blood flow that are necessary for the optimal interaction between VWF and its cleaving protease. The laboratory diagnosis of TTP is, therefore, still mainly clinical, being based on the presence of thrombocytopenia (due to increased intravascular consumption of blood platelets) and anemia (due to mechanical damage to red cells). There are still numerous questions to be answered. What are the pathogenic mechanisms of cases with normal or slightly reduced levels of ADAMTS13? What are the factors that periodically trigger the episodes of thrombocytopenia and anemia in the chronic recurrent forms, in the presence of constantly reduced levels of ADAMTS13? The behavior of anti-ADAMTS13autoantibodies following plasma exchange and therefore exposure to antigen (anamnestic response) is not well established. Likewise, the value of inducing immune tolerance by regular administrations of ADAMTS13, which will be possible when concentrates of the protease become available, has not been investigated.
Mannucci
Pier Mannuccio
PM
Department of Medicine and Medical Specialties, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milanand IRCCS Maggiore Hospital, Mangiagalli e Regina Elena Foundation, Milan, Italy. pmmannucci@libero.it
D051722:ADAM Proteins / Q000172:deficiency; D000071120:ADAMTS13 Protein; D006801:Humans; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D013921:Thrombocytopenia / Q000175:diagnosis; D013927:Thrombosis / Q000276:immunology
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human