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100 years ago Dr. Eli Moschcowitz described the first case of thrombotic thrombocytopenic purpura. For many decades there were no recognized treatment options, and the mortality rate was extremely high. At the beginning of the 1990 s, therapy with steroids and plasma exchange became increasingly popular, although the mortality rate was still over 20 %. It took until the turn of the millennium for the disease mechanisms (ADAMTS13-deficiency) to be decoded in Bern and New York, thus paving the way for new therapy options. It has now become clear that acquired TTP (iTTP) is an autoimmune disease, and the autoantibodies are directed against ADAMTS13, a protease that cleaves large von-Willebrand multimers. This causes a severe ADAMTS13-deficiency. The ultralarge multimers persist and bind platelets, resulting in microvascular thrombosis. This is distinguished from congenital TTP (cTTP), in which severe ADAMTS13-deficiency is caused by mutations in the ADAMTS13-gene (Upshaw-Schulman syndrome). In other forms of thrombotic microangiopathy (TMA, e. g. aHUS), severe ADAMTS13-deficiency does not occur. Two randomized controlled studies demonstrated the benefit of the selective bivalent anti-von-Willebrand factor (vWF) nanobody Caplacizumab, approved in 2019, in the treatment of iTTP. Various publications from national iTTP cohorts improved the data and showed consistent reductions in the time until platelet normalization, a reduction in refractory courses and exacerbations (especially when therapy is controlled according to ADAMTS13-activity) as well as evidence of reduced mortality. Modern therapeutic options include strategies for preemptive therapy for ADAMTS13-relapse as well as plasma exchange-free treatment. The use of recombinant ADAMTS13 may also expand the therapeutic options in iTTP patients in the future.
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http://dx.doi.org/10.1055/a-2360-8725 | DOI Listing |
Dtsch Med Wochenschr
November 2024
Klinik für Innere Medizin I - Abteilung für Hämatologie und Hämostaseologie, Medizinische Universität Wien, Österreich.
100 years ago Dr. Eli Moschcowitz described the first case of thrombotic thrombocytopenic purpura. For many decades there were no recognized treatment options, and the mortality rate was extremely high.
View Article and Find Full Text PDFHaematologica
September 2024
Département de Médecine interne, CHU Charles Nicolle, F-76000 Rouen, France; Université de Rouen, INSERM U1026 EnVI, F-76000 Rouen.
Cureus
August 2024
Internal Medicine, Honduran Social Security Institute, San Pedro Sula, HND.
J Med Econ
August 2024
Cencora, Conshohocken, PA, USA.
Aims: Thrombotic thrombocytopenic purpura (TTP) is an ultra-rare blood disorder, characterized by severe ADAMTS13 deficiency. Affected individuals present with potentially life-threatening acute events and may experience sub-acute and chronic TTP manifestations often resulting in long-term organ damage. Incremental symptom prevalence before, during, and after an acute event as well as healthcare resource utilization (HCRU) and costs during and after an acute event were compared between people with TTP and matched non-TTP controls.
View Article and Find Full Text PDFJ Clin Med
July 2024
The Roald Dahl Centre for Haemostasis and Thrombosis, Liverpool University Hospital NHS Trust, Liverpool L7 8XP, UK.
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