Thrombotic Thrombocytopenic Purpura: A Moving Target

Abstract

Almost 80 years after Eli Moschcowitz published the first description of the disease, most patients with idiopathic thrombotic thrombocytopenic purpura (TTP) were found to have acquired autoantibody inhibitors of the ADAMTS13 metalloprotease. Plasma ADAMTS13 normally cleaves von Willebrand factor within nascent platelet-rich thrombi, and ADAMTS13 deficiency allows unchecked thrombus growth to cause microangiopathic hemolysis, thrombocytopenia, and tissue infarction. At present, ADAMTS13 deficiency with a high-titer inhibitor level appears to be associated with an increased risk of early death and subsequent relapse. Thus, acquired ADAMTS13 deficiency identifies a specific mechanism of TTP and is a potential biomarker of disease activity or risk. At present, two major clinical questions in the field may be summarized as follows. First, by emphasizing TTP caused by ADAMTS13 deficiency, are we in danger of neglecting other causes that should be treated with plasma exchange? Second, should we treat asymptomatic patients who have severe ADAMTS13 deficiency to prevent future disease, and if so, how?The last few years have set the stage for a new approach to the management of thrombotic thrombocytopenic purpura (TTP). The criteria for idiopathic TTP have remained approximately constant, and plasma exchange is still the standard therapy. But the discovery of the ADAMTS13 metalloprotease has revolutionized our understanding of TTP and initiated a period of experimentation with regard to diagnosis and treatment. The management of TTP has been reviewed recently, 1 and I will not discuss it comprehensively. Instead, I will try to integrate the new knowledge about ADAMTS13 into a model for the pathogenesis of TTP, relate it to our experience in caring for these patients, and suggest where we may look for further advances during the next few years.

ADAMTS13 activity and antigen during therapy and follow-up of patients with idiopathic thrombotic thrombocytopenic purpura: correlation with clinical outcome

“…[1][2][3] Clinical biomarkers are needed to evaluate TTP patients more precisely and to provide the appropriate treatment accordingly. Deficiency of ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats) protease is a known risk factor in the pathogenesis of TTP.…”

Transplant-Associated Thrombotic Microangiopathy in Childhood

“…This protease is called as "ADAMTS13" and belongs to a disintegrin and metalloproteinase with thrombospondin type 1 repeats family (11)(12)(13)(14)(15). Severe ADAMTS13 deficiency (activity <5%) is seen in 33-100% of patients with primary TTP (16). Consequently, newly formed autoantibodies in primary TTP inhibit ADAMTS13 and thus www.intechopen.com…”

Púrpura trombocitopênica trombótica: o papel do fator von Willebrand e da ADAMTS13

“…Este fenômeno resulta em um quadro de anemia hemolítica microangiopática e sintomas que incluem fraqueza e adinamia, trombocitopenia acentuada, com aparecimento de petéquias e equimoses, febre e sintomas decorrentes da isquemia dos órgãos acometidos. 2 O comprometimento funcional dos órgãos está diretamente relacionado ao grau de isquemia. Se os trombos ocluírem a microcirculação do cérebro ou dos rins, as consequências podem ser muito graves.…”

“…Estas bactérias são produtoras de toxinas que se ligam às células endoteliais dos rins e comprometem a função dessas células. 2,3 Além da SHU, a PTT deve ser diferenciada de outras condições clínicas como anemia hemolítica autoimune, síndrome de Evans, pré-eclâmpsia, infecção pelo vírus da AIDS (HIV), sepse, coagulação intravascular disseminada, endocardites e vasculites secundárias a colagenoses para a intervenção terapêutica adequada. Cerca de metade dos pacientes com PTT relata a ocorrência de uma virose dias antes dos primeiros sintomas da doença.…”

“…Cerca de metade dos pacientes com PTT relata a ocorrência de uma virose dias antes dos primeiros sintomas da doença. 2,4 Fator von Willebrand (FvW) e ADAMTS13 O FvW é uma glicoproteína multimérica composta por subunidades idênticas de 270kD cada uma, contendo 2.050 aminoácidos. Apenas as células endoteliais e os megacarió-citos sintetizam e estocam FvW, e este tem uma vida média de vinte horas.…”