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.

scholarly journals Total Plasma Exchange for the Management of Thrombotic Thrombocytopenic Purpura in a 13-Year-Old Female – A Case Presentation

2021 ◽  
Vol 26 (3) ◽  
pp. 48-51
Author(s):  
Ioana Roxana Codru ◽  
Bogdan Ioan Vintilă ◽  
Alina Simona Bereanu ◽  
Alina Camelia Cătană ◽  
Mihai Sava
Keyword(s):  
Monoclonal Antibodies ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Neurological Impairment ◽  
Organ Damage ◽  
Biological Evaluation ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
First Line Therapy

Abstract Acquired thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy, affecting preferentially young women in their fourth decade. Intensive care admission is often required due to organ dysfunction development risk and for specific critical care measures (Plasma Exchange-PEX). In this article, we will discuss our experience with PEX in the treatment of TTP. Case report: A previously healthy 13-year-old female presented with neurological impairment, and suspicion of stroke. The head computed tomography (CT) scan revealed absence of acute intracranian pathology, and biological evaluation displayed severe thrombocytopenia and haemolytic anemia. After 24 hours, the neurological symptoms were remitted and suspicion of thrombotic thrombocytopenic purpura was raised. The presence of ADAMTS-13 antibodies and Moschcowitz’s pentad confirmed the diagnosis. Discussions: The distinctiveness of this case lies in the development of the disease in a 13-year-old person, though TTP usually occurs after the age of 40. The exact cause of ADAMTS-13 low activity could not be established. The use of a high dose of steroids and of plasma exchange is considered to be the first line therapy, with the use of monoclonal antibodies in refractory cases, as it was in our case. Conclusions: The primary end points of our management was to prevent organ damage and to achieve a platelet count greater than 150 000 /µL, as well as a normal or an almost normal lactate dehydrogenase. We achieved this by using high dose corticosteroid therapy, filtration of approximately 50 liters of plasma in 14 PEX session and by administration of monoclonal antibodies.

Anti-CD20 antibody in thrombotic thrombocytopenic purpura refractory to plasma exchange

2007 ◽  
Vol 37 (5) ◽  
pp. 329-332 ◽  
Author(s):  
K. V Chow ◽  
R Carroll ◽  
P Branley ◽  
K Nicholls ◽  
G Becker ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Cd20 Antibody ◽  
Anti Cd20

scholarly journals Acquired Deficiency of von Willebrand Factor-Cleaving Protease in a Patient With Thrombotic Thrombocytopenic Purpura

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2839-2846 ◽  
Author(s):  
Miha Furlan ◽  
Rodolfo Robles ◽  
Max Solenthaler ◽  
Bernhard Lämmle
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Protease Activity ◽  
Temporary Increase ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Plasma of patients with thrombotic thrombocytopenic purpura (TTP) has been shown to contain unusually large von Willebrand factor (vWF) multimers that may cause platelet agglutination in vivo. Fresh frozen plasma infusions and plasma exchange represent the most efficient therapy of acute TTP. A specific protease responsible for cleavage of vWF multimers has been recently isolated from normal human plasma and was found to be deficient in four patients with chronic relapsing TTP. We examined the activity of the vWF-cleaving protease in plasma samples collected over a period of 400 days from a further patient with recurrent episodes of TTP who was treated by plasma exchange, plasma infusion, vincristine, corticosteroid therapy, and splenectomy. Complete deficiency of the vWF-cleaving protease was established during the first episode of TTP. The ensuing normalization of the platelet count was associated with the appearance of the protease activity. Three months after remission from the initial TTP event, the vWF-cleaving protease again disappeared and the platelet count gradually decreased. Relapses of severe thrombocytopenia occurred 7 and 11 months after the first acute episode of TTP. Deficient protease activity was associated with the presence in the patient plasma of an inhibitor that was found to be an IgG. Plasma exchange/infusion was followed by a temporary increase in the antibody titer, whereas treatment with vincristine led to a recovery of the platelet count without affecting the inhibitor concentration. Splenectomy and corticosteroid treatment resulted in disappearance of the autoantibody and normalization of the protease activity and of the platelet count. Our data suggest that the thrombocytopenia in this patient with TTP was associated with a lack of the vWF-cleaving protease activity depleted by an autoimmune mechanism. This case, together with our previously reported patients, leads us to conclude that acquired as well as constitutional deficiency of the vWF-cleaving protease may predispose to TTP.

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.

Long-term Efficacy of Rituximab Treatment in Thrombotic Thrombocytopenic Purpura

2011 ◽  
Vol 07 (02) ◽  
pp. 143
Author(s):  
Jens M Chemnitz ◽  
Michael Hallek ◽  
Christof Scheid ◽  
◽  
◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Case Reports ◽  
Therapeutic Option ◽  
Case Series ◽  
Current Data ◽  
Thrombocytopenic Purpura ◽  
Long Term Follow Up

The use of therapeutic plasma exchange has reduced mortality rates in thrombotic thrombocytopenic purpura (TTP) from 90 to 10–20%. However, TTP is a potentially lethal disorder, and management of patients with TTP refractory to plasma exchange or frequently recurrent disease is difficult. In those cases, rituximab might be a therapeutic option, although current data are based primarily on case reports and smaller case series. While initial response rates to rituximab are reported to be high, long-term follow-up data of patients treated with rituximab are rare; however, it is important to estimate the safety and benefit of this treatment. In this article we focus on current experience with rituximab in the treatment of TTP, including recent results with long-term follow-up.

scholarly journals Thrombotic thrombocytopenic purpura (TTP) or Moschowitz syndrome: a true hematologic emergency

2012 ◽  
pp. 227-237
Author(s):  
Deborah Melis ◽  
Gianluca Michelis ◽  
Marcello Brignone ◽  
Marina Cavaliere ◽  
Rodolfo Tassara
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Medical Emergency ◽  
Prognostic Indicators ◽  
Late Relapse ◽  
Inherited Disorders ◽  
Thrombocytopenic Purpura ◽  
Anti Cd20 ◽  
Von Willebrand

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by congenital or inherited disorders involving the processing of the ultra-large forms of von Willebrand factor. As a result, platelet-rich microthrombi form in the small arterial vessels of various organs, particularly those of the brain, heart, and kidneys. The idiopathic autoimmune form of TTP is the most common. There are various subgroups of acquired TTP associated with HIV infection, sepsis, pregnancy, autoimmune disease, various disseminated malignancies, and drugs. If not promptly treated, TTP is associated with high mortality, making it a true medical emergency. Materials and methods: The article is based on a review of the literature published between January and October of 2009. Its aim is to clarify the diagnosis, treatment, and follow-up of TTP. Results: Diagnostic criteria include the presence of microangiopathic hemolytic anemia associated with thrombocytopenia in the absence of other obvious causes. Assays of ADAMTS13 activity and titration of acquired antibodies against this enzyme are indicated in the follow-up of disease and as prognostic indicators. Treatment centers around daily plasma exchange associated with immunosuppressant drug therapy, particularly steroids and more recently the monoclonal anti-CD20 antibody rituximab. Discussion: Despite improved treatment, TTP is still associated with significant mortality (10—20%), particularly when plasma exchange is initiated late. Relapse also occurs in a substantial proportion of patients (10—40%) although the frequency of this outcome may be reduced by rituximab therapy.

ADAMTS13 activity in thrombotic thrombocytopenic purpura–hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Sara K. Vesely ◽  
James N. George ◽  
Bernhard Lämmle ◽  
Jan-Dirk Studt ◽  
Lorenzo Alberio ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Outcomes ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Initial Management ◽  
Severe Deficiency ◽  
Uremic Syndrome ◽  
Adamts13 Deficiency

Abstract Initial management of patients with thrombotic thrombocytopenic purpura—hemolytic uremic syndrome (TTP-HUS) is difficult because of lack of specific diagnostic criteria, high mortality without plasma exchange treatment, and risks of plasma exchange. Although severe ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) deficiency may be specific for TTP, the role of ADAMTS13 activity measurements for initial management decisions is unknown. ADAMTS13 was measured before beginning plasma exchange treatment in 142 (88%) of 161 consecutive patients with clinically diagnosed TTP-HUS with assignment to 1 of 4 categories: less than 5% (severe deficiency), 5% to 9%, 10% to 25%, and more than 25%. Eighteen (13%) of 142 patients had severe ADAMTS13 deficiency. Among 6 predefined clinical categories (stem cell transplantation, pregnant/postpartum, drug association, bloody diarrhea, additional/alternative disorder, idiopathic), severe deficiency occurred only among pregnant/postpartum (2 of 10) and idiopathic (16 of 48) patients. The presenting features and clinical outcomes of the 16 patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency were variable and not distinct from the 32 patients with idiopathic TTPHUS who did not have severe ADAMTS13 deficiency. Many patients in all ADAMTS13 activity categories apparently responded to plasma exchange treatment. Therefore, severe ADAMTS13 deficiency does not detect all patients who may be appropriately diagnosed with TTP-HUS and who may respond to plasma exchange treatment. (Blood. 2003;102:60-68)

Platelets: Thrombotic Thrombocytopenic Purpura

Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 315-334 ◽  
Author(s):  
James N. George ◽  
J. Evan Sadler ◽  
Bernhard Lämmle
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Approach ◽  
Adamts13 Activity ◽  
Extensive Experience ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Adamts13 Deficiency ◽  
And Function ◽  
Von Willebrand

Abstract Abnormalities of plasma von Willebrand factor (VWF) have been recognized to be associated with thrombotic thrombocytopenic purpura (TTP) for over 20 years. Patients with chronic, relapsing TTP have VWF multimers that are larger than normal, similar in size to those secreted by cultured endothelial cells. Recent observations have documented that a deficiency of a VWF-cleaving protease (termed ADAMTS13) may be responsible for the presence of these unusually large VWF multimers. Multiple mutations of the ADAMTS13 gene can result in ADAMTS13 deficiency and cause congenital TTP; autoantibodies neutralizing ADAMTS13 protease activity have been associated with acquired TTP. In Section I, Dr. Evan Sadler reviews the structure, biosynthesis, and function of the ADAMTS13 protease. He describes the mutations that have been identified in congenital TTP and describes the relationship of ADAMTS13 deficiency to the development of both congenital and acquired TTP. Dr. Sadler postulates that the development of TTP may be favored by conditions that combine increased VWF secretion, such as during the later stages of pregnancy, and decreased ADAMTS13 activity. In Section II, Dr. Bernhard Lämmle describes the assay methods for determining ADAMTS13 activity. Understanding the complexity of these methods is essential for understanding the difficulty of assay performance and the interpretation of assay data. Dr. Lämmle describes his extensive experience measuring ADAMTS13 activity in patients with TTP as well as patients with acute thrombocytopenia and severe illnesses not diagnosed as TTP. His data suggest that a severe deficiency of ADAMTS13 activity (< 5%) is a specific feature of TTP. However, he emphasizes that, although severe ADAMTS13 deficiency may be specific for TTP, it may not be sensitive enough to identify all patients who may be appropriately diagnosed as TTP and who may respond to plasma exchange treatment. In Section III, Dr. James George describes the evaluation and management of patients with clinically suspected TTP, as well as adults who may be described as having hemolytic-uremic syndrome (HUS). Dr. George presents a classification of TTP and HUS in children and adults. Appropriate evaluation and management are related to the clinical setting in which the diagnosis is considered. A clinical approach is described for patients in whom the diagnosis of TTP or HUS is considered (1) following bone marrow transplantation, (2) during pregnancy or the postpartum period, (3) in association with drugs which may cause TTP either by an acute immune-mediated toxicity or a dose-related toxicity, (4) following a prodrome of bloody diarrhea, (5) in patients with autoimmune disorders, and (6) in patients with no apparent associated condition who may be considered to have idiopathic TTP. Patients with idiopathic TTP appear to have the greatest frequency of ADAMTS13 deficiency and appear to be at greatest risk for a prolonged clinical course and subsequent relapse. Management with plasma exchange has a high risk of complications. Indications for additional immunosuppressive therapy are described.

scholarly journals How I treat patients with thrombotic thrombocytopenic purpura–hemolytic uremic syndrome

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1223-1229 ◽  
Author(s):  
James N. George
Keyword(s):  
Renal Failure ◽  
Hemolytic Uremic Syndrome ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Survival Rates ◽  
Thrombocytopenic Purpura ◽  
Long Term Follow Up ◽  
Uremic Syndrome

Abstract Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are, in adults, clinically and pathologically indistinguishable except for the severity of renal failure. They are best described as a single disorder, TTP-HUS, because the diagnostic evaluation and initial management are the same. Treatment with plasma exchange, available for more than 20 years, has dramatically altered the course of disease in adults with TTP-HUS. Plasma exchange has improved survival rates from 10% to between 75% and 92%, creating urgency for the initiation of treatment. This has resulted in decreased stringency of diagnostic criteria, which in turn has resulted in a broader spectrum of disorders for which the diagnosis of TTP-HUS is considered. Long-term follow-up has revealed increasing frequencies of relapse and of chronic renal failure. Although the increased survival rate is dramatic and recent advances in understanding the pathogenesis of these syndromes are remarkable, clinical decisions remain empirical. Therefore, the management decisions for patients with suspected TTP-HUS rely on individual experience and opinion, resulting in many different practice patterns. Multipractice clinical trials are required to define optimal management.

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