Review
Genetics & Heredity
Sanober Nusrat, Kisha Beg, Osman Khan, Arpan Sinha, James George
Summary: Hereditary thrombotic thrombocytopenic purpura (hTTP), also known as Upshaw-Schulman syndrome, is a rare genetic disorder caused by mutations in the ADAMTS13 gene that leads to decreased or absent production of the plasma von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13. The disease can cause thrombocytopenia, impairment of blood circulation, and organ damage. Prophylaxis with plasma infusions or plasma-derived factor VIII products is the primary treatment for preventing acute episodes.
Review
Medicine, General & Internal
Senthil Sukumar, Bernhard Lammle, Spero R. Cataland
Summary: TTP is a rare but dangerous disorder characterized by hemolysis, thrombocytopenia, and ischemic damage, often caused by ADAMTS13 deficiency. Front-line treatment typically involves plasma exchange and immunosuppression, as well as drugs like rituximab and caplacizumab. Refractory cases may require alternative therapies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Hematology
Charlotte Dekimpe, Elien Roose, Kazuya Sakai, Claudia Tersteeg, Simon F. De Meyer, Karen Vanhoorelbeke
Summary: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare disorder caused by a deficiency in ADAMTS-13. Current management involves plasma infusions of ADAMTS-13, but this is a demanding therapy with frequent allergic reactions. Gene therapy has the potential to provide a curative therapy for cTTP, and ongoing research is focused on various preclinical approaches. This review highlights the challenges of developing a gene therapy product for cTTP and provides an overview of the current state of preclinical gene therapy studies.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Medicine, General & Internal
Giovanni Tiscia, Maria Teresa Sartori, Gaetano Giuffrida, Angelo Ostuni, Nicola Cascavilla, Daniela Nicolosi, Cosima Battista, Teresa Maria Santeramo, Lorella Melillo, Giulio Giordano, Filomena Cappucci, Lucia Fischetti, Elena Chinni, Giuseppe Tarantini, Anna Cerbo, Antonella Bertomoro, Fabrizio Fabris, Elvira Grandone
Summary: Immune-mediated thrombotic thrombocytopenic purpura is a rare and challenging hematological disease caused by the antibody anti-ADAMTS13. Despite a significant decrease in mortality rate in recent years, fatalities are still unacceptable. Early detection and treatment are crucial for improving patient prognosis.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Immunology
Zhouhan Wang, Hao Xu, Beiqing Gu, Yanqi Jin, Tianyuan Wang, Jindi Ma, Yingfeng Lu, Xiaopeng Yu, Beiwen Zheng, Yimin Zhang
Summary: This study reported the first case of acquired TTP induced by Salmonella enterica infection in an AIDS patient, and identified FlRd protein encoded by norV gene in the Salmonella genome as a potential trigger for TTP. FlRd was found to be highly conservative, functional, and widespread in both S. enterica and Enterobacteriaceae.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Medicine, General & Internal
Quintijn Bonnez, Kazuya Sakai, Karen Vanhoorelbeke
Summary: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare medical emergency that requires early and accurate diagnosis. ADAMTS13 deficiency is the underlying cause, and diagnostic strategies involve monitoring ADAMTS13 parameters. In addition to conventional ADAMTS13 testing, evaluating ADAMTS13 conformation and measuring non-ADAMTS13 parameters can assist in the diagnosis and follow-up of iTTP patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Cell Biology
Zoe Markham-Lee, Neil Morgan, Jonas Emsley
Summary: ADAMTS13 is a plasma metalloprotease that cleaves VWF to maintain hemostasis, and its mutations are associated with Thrombotic Thrombocytopenic Purpura. Molecular characterization of ADAMTS13 is important for understanding the mechanisms of TTP.
Article
Immunology
Yanming Cui, Jianbo Wei, Xiang Peng
Summary: Vaccination in patients with autoimmune diseases is controversial due to the possibility of thrombotic thrombocytopenic purpura. This case report describes a patient with systemic lupus erythematosus who developed thrombotic thrombocytopenic purpura after rabies vaccination. Prompt identification and treatment saved the patient from danger. This highlights the potential unexpected adverse effects of attenuated vaccines in patients on long-term immunosuppressive drugs and with autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Sruthi Selvakumar, Angela Liu, Shruti Chaturvedi
Summary: Advances in diagnosis and treatment have significantly improved survival rates of acute immune thrombotic thrombocytopenic purpura (iTTP) and changed it from an acute fatal condition to a chronic relapsing disorder. iTTP survivors are at risk of various adverse outcomes, including higher rates of all-cause mortality, cardiovascular diseases, and comorbidities like obesity and autoimmune disorders. Women with iTTP face risks of recurrence, preeclampsia, and other complications during subsequent pregnancies. ADAMTS13 activity during remission is an important factor for predicting relapse and other outcomes. This review summarizes the epidemiology and mechanisms of adverse long-term sequelae of iTTP, current best practices in survivorship care, and research agenda for improving long-term outcomes.
FRONTIERS IN MEDICINE
(2023)
Article
Hematology
Adrien Picod, Agnes Veyradier, Paul Coppo
Summary: iTTP is a rare and life-threatening disease currently treated with TPE and immunosuppression, while caplacizumab, a new treatment, shows faster platelet count recovery, decreased adverse outcomes, and reduced burden of care by inhibiting platelet aggregation and microthrombi formation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Leydi Carolina Velasquez Pereira, Elien Roose, Nuno A. G. Graca, Gyorgy Sinkovits, Kadri Kangro, Berangere S. Joly, Edwige Tellier, Gilles Kaplanski, Tanja Falter, Charis Von Auer, Heidi Rossmann, Hendrik B. Feys, Marienn Reti, Zoltan Prohaszka, Bernhard Lammle, Jan Voorberg, Paul Coppo, Agnes Veyradier, Simon F. De Meyer, Andres Mannik, Karen Vanhoorelbeke
Summary: This study identified three hotspot regions (amino acid regions 588-592, 602-610, and 657-666) in the spacer domain of ADAMTS13 that are targeted by anti-spacer autoantibodies found in a large cohort of iTTP patients.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Medicine, General & Internal
Eleni Gavriilaki, Emmanuel Nikolousis, Eudoxia-Evaggelia Koravou, Sotiria Dimou-Besikli, Charalampos Kartsios, Anna Papakonstantinou, Anastasia Mpanti, Charalampos Pontikoglou, Christina Kalpadaki, Aikaterini Bitsani, Ilianna Tassi, Tasoula Touloumenidou, Thomas Chatziconstantinou, Maria Papathanasiou, Antonia Syrigou, Eleutheria Ztriva, Georgia Kaiafa, Evdokia Mandala, Zois Mellios, Dimitrios Karakasis, Alexandra Kourakli, Argiris Symeonidis, Eleni Kapsali, Helen H. Papadaki, Chrysavgi Lalayanni, Ioanna Sakellari
Summary: A multicenter real-world study was conducted to assess the safety and efficacy of caplacizumab in treating immune thrombotic thrombocytopenic pupura (iTTP). The results showed that caplacizumab is safe and effective in treating iTTP, including cases refractory to plasma exchange. Discontinuation of dosing guided by ADAMTS13 activity can lower the relapse rate.
FRONTIERS IN MEDICINE
(2023)
Article
Hematology
Konstantine Halkidis, Chan Meng, Szumam Liu, Leland Mayne, Don L. Siegel, X. Long Zheng
Summary: Antibodies binding to ADAMTS13 are crucial for the development of iTTP. Inhibitory antibodies affect the enzyme turnover rate rather than substrate recognition of VWF. The binding of inhibitory antibodies to ADAMTS13's catalytic domain affects the conformation and leads to impaired VWF cleavage. This study provides new insights into the mechanism of antibody-mediated inhibition of ADAMTS13 and pathogenesis of iTTP.
Article
Hematology
Jana van den Berg, Johanna A. Kremer Hovinga, Claudia Pfleger, Inga Hegemann, Gregor Stehle, Andreas Holbro, Jan-Dirk Studt
Summary: Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disease that can be treated with the anti-CD38 antibody daratumumab to eradicate persistent ADAMTS13 inhibitory autoantibodies and restore normal ADAMTS13 activity.
Article
Cell Biology
Bryan Tordon, Theodore E. Warkentin, Jane C. Moore, Donald M. Arnold
Summary: TTP rarely complicates acute inflammatory conditions such as surgery, however, post-cardiac surgery TTP may have a connection with preoperative anti-ADAMTS13 autoantibodies.