scholarly journals Current and Future Perspectives on ADAMTS13 and Thrombotic Thrombocytopenic Purpura

2020 ◽  
Vol 40 (03) ◽  
pp. 322-336 ◽  
Author(s):  
Elien Roose ◽  
Bérangère S. Joly
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Diagnostic Assays ◽  
Severe Deficiency ◽  
Targeted Treatments ◽  
Life Threatening ◽  
Thrombospondin Type 1 Repeats

AbstractThrombotic thrombocytopenic purpura (TTP) is a rare, relapsing, and life-threatening disorder with an annual incidence of 10 cases per million people. TTP is a thrombotic microangiopathy characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia. The disease is caused by a severe deficiency of the enzyme ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), which can either be acquired, mainly by autoantibodies targeting ADAMTS13, or congenital due to mutations in the ADAMTS13 gene. Thanks to the establishment of national registries worldwide, fundamental and translational research, major advances have been made on the diagnosis, treatment, and fundamental understanding of TTP, since the description of the first TTP case almost 100 years ago. The introduction of therapeutic plasma exchange in the 1970s has significantly improved patient survival, but novel diagnostic assays, targeted treatments (rituximab, caplacizumab, recombinant ADAMTS13), and the unraveling of both ADAMTS13 function and TTP pathophysiology should help to further improve the patients' quality of life. However, differential diagnosis of TTP remains challenging and still a lot of questions remain unanswered to completely understand this rare and devastating disease.

scholarly journals THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) AND MODERN APPROACH TO ITS INVESTIGATION AND TREATMENT

2019 ◽  
pp. 12-13
Author(s):  
K. Ukleba ◽  
L. Gvetadze
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Modern Approach ◽  
Severe Deficiency ◽  
Life Threatening ◽  
Adamts13 Deficiency ◽  
Von Willebrand ◽  
Willebrand Factor

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet rich-thrombi. TTP is specifically related to a severe deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), the specific von Willebrand factor-cleaving protease. ADAMTS13 deficiency is most frequently acquired via ADAMTS13 autoantibodies, but rarely, it is inherited via mutations of the ADAMTS13 gane. The first acute episode of TTP usually occurs during adulthood, with a predominant anti – ADAMTS13 autoimmune etiology. In rare cases, however, TTP begins as soon as childhood, with frequent inherited forms. TTP is 2 – fold more frequent in women, and its outcome is characterized by a relapsing tendency.

scholarly journals Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5888-5897 ◽  
Author(s):  
Marie Moatti-Cohen ◽  
Céline Garrec ◽  
Martine Wolf ◽  
Pierre Boisseau ◽  
Lionel Galicier ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
National Registry ◽  
Cross Sectional ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Specific Subgroup ◽  
Life Threatening ◽  
Adamts13 Deficiency ◽  
Sectional Analysis

Abstract Pregnancy may be complicated by a rare but life-threatening disease called thrombotic thrombocytopenic purpura (TTP). Most cases of TTP are due to an acquired autoimmune or hereditary (Upshaw-Schulman syndrome [USS]) severe deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13). In the present study, we performed a cross-sectional analysis of the national registry of the French Reference Center for Thrombotic Microangiopathies from 2000-2010 to identify all women who were pregnant at their initial TTP presentation. Among 592 adulthood-onset TTP patients with a severe ADAMTS13 deficiency, 42 patients with a pregnancy-onset TTP were included. Surprisingly, the proportion of USS patients (n = 10 of 42 patients [24%]; confidence interval, 13%-39%) with pregnancy-onset TTP was much higher than that in adulthood-onset TTP in general (less than 5%) and was mostly related to a cluster of ADAMTS13 variants. In the present study, subsequent pregnancies in USS patients not given prophylaxis were associated with very high TTP relapse and abortion rates, whereas prophylactic plasmatherapy was beneficial for both the mother and the baby. Pregnancy-onset TTP defines a specific subgroup of patients with a strong genetic background. This study was registered at www.clinicaltrials.gov as number NCT00426686 and at the Health Authority, French Ministry of Health, as number P051064.

scholarly journals Clinical experience in treatment of thrombotic thrombocytopenic purpura - hemolytic uremic syndrome with 28 patients

2013 ◽  
Vol 60 (1) ◽  
pp. 29-38
Author(s):  
Dragica Vucelic ◽  
Zoran Rajic ◽  
Nebojsa Savic ◽  
Danijela Mikovic ◽  
Zivko Budisin ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Response Rate ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Uremic Syndrome ◽  
Design And Methods ◽  
Thrombospondin Type 1 Repeats

Background: Neither optimal treatment nor significance of ADAMTS13 (A Desintegrin And Metalloprotease with ThromboSpondin type 1 repeats) activity for diagnosis and therapy of thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) have not been defined yet. The aim of the report is to analyze response to different volumes of plasma exchange (PE), and relationship to ADAMTS13. Design and methods: 28 patients clinically diagnosed with idiopathic TTP (n=18), secondary TTP (n=4), atypical HUS (n=3) and typical HUS (n=3) manifested 31 acute episodes. Patients were treated with PE in 26, and with plasma transfusion in 5 episodes with additional different therapies. Results: PE volumes were as follows: 1 in 7, 1.5 in 3, 2 in 14, and intensifying schedule (1 to 1.5) in 2 episodes. Procedure number was lower in patients treated with 2 and 1.5 (p=0.019) than in those treated with 1 volume exchange and PE intensifying, respectively (p=0.010). PE response rate was 25/26 (96.15%). Exacerbation frequency was higher in idiopathic TTP patients (3/19) treated with 1 compared with patients treated with >1 volume exchange (p=0.003). Survival rate was 25/28 (89.29%). ADAMTS13 activity was reduced in 22 with severe deficiency in 14 patients. Conclusion: Patients responded to different treatments regardless of ADAMTS13 activity, requiring less PEs with larger volume exchanges.

scholarly journals How I treat thrombotic thrombocytopenic purpura in pregnancy

Blood ◽  
2020 ◽  
Vol 136 (19) ◽  
pp. 2125-2132
Author(s):  
Barbara Ferrari ◽  
Flora Peyvandi
Keyword(s):  
Differential Diagnosis ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Current Knowledge ◽  
Fetal Outcome ◽  
Subsequent Pregnancy ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Life Threatening ◽  
High Index Of Suspicion ◽  
In Pregnancy

Abstract Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening thrombotic microangiopathy (TMA) caused by acquired or congenital severe deficiency of ADAMTS13. Pregnancy is a recognized risk factor for precipitating acute (first or recurrent) episodes of TTP. Differential diagnosis with other TMAs is particularly difficult when the first TTP event occurs during pregnancy; a high index of suspicion and prompt recognition of TTP are essential for achieving a good maternal and fetal outcome. An accurate distinction between congenital and acquired cases of pregnancy-related TTP is mandatory for safe subsequent pregnancy planning. In this article, we summarize the current knowledge on pregnancy-associated TTP and describe how we manage TTP during pregnancy in our clinical practice.

scholarly journals Thrombotic Thrombocytopenic Purpura Following Honeybee Envenomation: A Case Report

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Zahra Khalighi ◽  
Golnaz Azami ◽  
Elham Shafiei ◽  
Ali Sahebi ◽  
Aliashraf Mozafari
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Case Reports ◽  
Major Complication ◽  
The Body ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Toxic Reaction ◽  
Bee Sting ◽  
Life Threatening ◽  
Underlying Diseases

Background: Thrombotic Thrombocytopenic Purpura (TTP) is a rare and life-threatening disorder characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, fever, renal dysfunction, and neurological deficient. TTP leads to the formation of blood clots in small blood vessels throughout the body. TTP is associated with many risk factors such as pregnancy, HIV, cancer, lupus, and infections. Recently there have been few published case reports of bee sting associated TTP.Methods: A 67-year-old man from a rural area of the Southwest Province of Iran, Ilam, was referred to the academic general hospital because of fever, chills, sweating, vomiting and dizziness following the honeybee sting on his body. Results: this study showed that,multiple co-morbidities including CVD and diabetes, along with coagulation abnormalities after honeybee stings, seriously exacerbated patient hemodynamic status.Conclusion: TTP, as a major complication due to the toxic reaction of a large number of bee stings with underlying diseases in patients, should be given more attention.

scholarly journals Efficacy and Safety of Rituximab for Refractory and Relapsing Thrombotic Thrombocytopenic Purpura: A Cohort of 10 Cases

2015 ◽  
Vol 8 ◽  
pp. CMBD.S25326 ◽  
Author(s):  
Halima El Omri ◽  
Ruba Y. Taha ◽  
Amna Gamil ◽  
Firyal Ibrahim ◽  
Hisham Al Sabah ◽  
...  
Keyword(s):  
Complete Remission ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Dose Range ◽  
Thrombocytopenic Purpura ◽  
Clinical Criteria ◽  
Severe Deficiency ◽  
Life Threatening ◽  
Multiple Relapses

Objective Idiopathic thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder mediated by autoantibodies directed against ADAMTS13. This provides a rationale for the use of rituximab in this disorder. We report our experience and the outcome of 10 cases of TTP (9 refractory and 1 relapsing) successfully treated with rituximab in combination with plasma exchange (PE) and other immunosuppressive treatments. Methods The diagnosis of TTP was based on clinical criteria and supported by severe deficiency of ADAMTS13 activity and presence of inhibitors in seven cases. Rituximab was started after a median of 18.6 sessions of PE (range: 5-35) at the dose of 375 mg/m2/week for 4-8 weeks. Results Complete remission was achieved in all patients after a median time of 14.4 days of the first dose (range: 6-30). After a median follow-up of 30 months (range: 8-78), eight patients were still in remission and two developed multiple relapses, treated again with the same therapy, and achieved complete responses; they are alive, and in complete remission after a follow-up of 12 and 16 months. Conclusion Rituximab appears to be a safe and effective therapy for refractory and relapsing TTP. However, longer follow-up is recommended to assess relapse and detect possible long-term side effects of this therapy.

scholarly journals Thrombotic thrombocytopenic purpura: An unusual presentation with intracranial bleed

2021 ◽  
pp. 436-438
Author(s):  
Shaik Mohammad Tahaseen ◽  
Ravi Kirti ◽  
Subhash Kumar
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Peripheral Blood Smear ◽  
Severe Thrombocytopenia ◽  
Provisional Diagnosis ◽  
Thrombocytopenic Purpura ◽  
Intracranial Bleed ◽  
Life Threatening ◽  
High Index Of Suspicion ◽  
The Brain ◽  
Tomography Scan

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet-rich thrombi. We present the case of a 44-year-old lady who presented with severe thrombocytopenia and anemia that did not respond to repeated transfusions and steroids. Non-contrast computed tomography scan of the brain revealed an intracranial bleed. Schistocytes were seen on the peripheral blood smear. A provisional diagnosis of TTP was made. Plasmapheresis could not be done due to her deteriorating hemodynamic status. She succumbed to her illness in spite of the best possible efforts. This case highlights the need for keeping a high index of suspicion for TTP as early diagnosis and prompt initiation of plasmapheresis are crucial for preventing death.

Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4514-4519 ◽  
Author(s):  
Christoph Klaus ◽  
Barbara Plaimauer ◽  
Jan-Dirk Studt ◽  
Friedrich Dorner ◽  
Bernhard Lämmle ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Adamts13 Deficiency ◽  
Multiple Domains ◽  
Von Willebrand ◽  
Recombinant Fragments ◽  
Willebrand Factor

Abstract Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 can lead to thrombotic thrombocytopenic purpura (TTP), a disease associated with the widespread formation of platelet-rich thrombi in many organs. Autoantibodies that inactivate ADAMTS13 are the most frequent cause of acquired TTP. Little is known about epitope specificity and reactivity of anti-ADAMTS13 antibodies. In this study, a series of ADAMTS13 domains were expressed in Escherichia coli, and the reactivity of purified recombinant fragments with anti-ADAMTS13 auto-antibodies from 25 patients with severe ADAMTS13 deficiency was evaluated in vitro. All TTP plasmas contained antibodies directed against the cysteine-rich spacer (cys-rich/spacer) domain of ADAMTS13. In the plasma of 3 patients, antibodies were detected that reacted exclusively with the cys-rich/spacer domain, underscoring the importance of this region for functional activity of ADAMTS13. In 64% of the plasmas, antibodies reacted with the 2 CUB domains, and in 56% they reacted with the isolated first thrombospondin type 1 (TSP-1) repeat and with the compound fragment consisting of the catalytic, the disintegrin-like, and the TSP1-1 domain. Less frequently, in 28% of the plasmas, antibodies reacted with the TSP1 repeats 2 to 8. Unexpectedly, antibodies reacted with the propeptide region in 20% of the plasmas. In conclusion, this study shows that even though anti-ADAMTS13 autoantibodies react with multiple domains of the protease, the cys-rich/spacer domain is consistently involved in antibody reactivity. (Blood. 2004;103:4514-4519)

scholarly journals Thrombotic thrombocytopenic purpura

Blood ◽  
2017 ◽  
Vol 129 (21) ◽  
pp. 2836-2846 ◽  
Author(s):  
Bérangère S. Joly ◽  
Paul Coppo ◽  
Agnès Veyradier
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
New Drugs ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Immune Modulators ◽  
First Line Therapy ◽  
Severe Deficiency ◽  
Long Term Follow Up ◽  
Anti Cd20

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet rich-thrombi. TTP is specifically related to a severe deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), the specific von Willebrand factor-cleaving protease. ADAMTS13 deficiency is most frequently acquired via ADAMTS13 autoantibodies, but rarely, it is inherited via mutations of the ADAMTS13 gene. The first acute episode of TTP usually occurs during adulthood, with a predominant anti-ADAMTS13 autoimmune etiology. In rare cases, however, TTP begins as soon as childhood, with frequent inherited forms. TTP is ∼2-fold more frequent in women, and its outcome is characterized by a relapsing tendency. Rapid recognition of TTP is crucial to initiate appropriate treatment. The first-line therapy for acute TTP is based on daily therapeutic plasma exchange supplying deficient ADAMTS13, with or without steroids. Additional immune modulators targeting ADAMTS13 autoantibodies are mainly based on steroids and the humanized anti-CD20 monoclonal antibody rituximab. In refractory or unresponsive TTP, more intensive therapies including twice-daily plasma exchange; pulses of cyclophosphamide, vincristine, or cyclosporine A; or salvage splenectomy are considered. New drugs including N-acetylcysteine, bortezomib, recombinant ADAMTS13, and caplacizumab show promise in the management of TTP. Also, long-term follow-up of patients with TTP is crucial to identify the occurrence of other autoimmune diseases, to control relapses, and to evaluate psychophysical sequelae. Further development of both patients’ registries worldwide and innovative drugs is still needed to improve TTP management.

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