scholarly journals Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura

Blood ◽  
2018 ◽  
Vol 132 (20) ◽  
pp. 2143-2153 ◽  
Author(s):  
Matthieu Jestin ◽  
Ygal Benhamou ◽  
An-Sofie Schelpe ◽  
Elien Roose ◽  
François Provôt ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Relapse Rate ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
Key Points ◽  
Long Term Follow Up ◽  
Adamts13 Deficiency ◽  
Risk Balance

Key Points TTP patients who display persistent and severe ADAMTS13 deficiency after remission have a relapse rate of 74% during long-term follow-up. Preemptive rituximab can decrease TTP relapses in 85% of patients with a favorable benefit-risk balance.

scholarly journals Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura

Blood ◽  
2020 ◽  
Author(s):  
Elien Roose ◽  
An-Sofie Schelpe ◽  
Edwige Tellier ◽  
György Sinkovits ◽  
Bérangère S Joly ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Follow Up Study ◽  
Open Conformation ◽  
Immune Mediated ◽  
Long Term Follow Up ◽  
Donor Plasma

Recently, we showed that during the acute phase of immune-mediated thrombotic thrombocytopenic purpura (iTTP), ADAMTS13 circulates in an open conformation. Although the cause of this conformational change in acute iTTP remains elusive, ADAMTS13 is mainly closed in iTTP patients (i) in remission with an ADAMTS13 activity >50% and undetectable anti-ADAMTS13 autoantibodies, and (ii) after rituximab treatment, suggesting a role for anti-ADAMTS13 autoantibodies. Therefore, IgGs from 18 acute iTTP patients were purified and added to closed ADAMTS13 in healthy donor plasma. This resulted in open ADAMTS13 in 14/18 (78%) samples, proving that indeed anti-ADAMTS13 autoantibodies can induce an open ADAMTS13 conformation. To further elucidate the conformation of ADAMTS13 in iTTP patients, we studied a novel iTTP patient cohort (n=197) that also included plasma samples of iTTP patients in remission where ADAMTS13 activity was <50%. The open ADAMTS13 conformation was not only found during acute iTTP but also in patients in remission with an ADAMTS13 activity <50% and in half of the patients with an ADAMTS13 activity >50%, although free anti-ADAMTS13 autoantibodies were not always detected. Thus open ADAMTS13 is not only a hallmark of acute iTTP, but also a novel biomarker to detect subclinical iTTP in patients in remission. Finally, a long term follow-up study in one iTTP patient showed that the open conformation precedes a severe drop in ADAMTS13 activity. In conclusion, we have shown that anti-ADAMTS13 autoantibodies from iTTP patients induce an open ADAMTS13 conformation. Most importantly, an open ADAMTS13 conformation is a biomarker for subclinical iTTP and could become an important tool in TTP management.

scholarly journals Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 604-609 ◽  
Author(s):  
James N. George ◽  
Zayd L. Al-Nouri
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Features ◽  
Clinical Decision ◽  
Response To Treatment ◽  
Long Term Outcomes ◽  
Thrombocytopenic Purpura ◽  
Long Term Follow Up ◽  
Adamts13 Deficiency

Abstract Evaluation and management of patients with suspected thrombotic thrombocytopenic purpura (TTP) continue to be a critical challenge for hematologists. The diagnostic criteria are not precise, often causing uncertainty about whether it is appropriate to initiate plasma exchange (PEX), the essential treatment for TTP. Initiation of PEX remains a clinical decision; severe ADAMTS13 (< 10% activity) deficiency alone is neither sufficiently sensitive nor specific for the diagnosis of TTP. However, patients who do have severe acquired ADAMTS13 deficiency define the characteristic clinical features of TTP, the response to treatment, and the long-term outcomes. Patients with severe acquired ADAMTS13 deficiency are predominantly young women and the relative frequency of blacks is increased. Patients may present with only microangiopathic hemolytic anemia and thrombocytopenia, neurologic and renal abnormalities are often not present, fever rarely occurs; the complete “pentad” of these clinical features almost never occurs in current practice. Response to PEX is typically rapid but may not be sustained when PEX is stopped. Use of corticosteroids and rituximab has decreased the number of PEX treatments required to achieve a remission and has resulted in fewer PEX-related major complications. Relapse (in approximately 40% of patients) may be the most apparent risk after recovery, but long-term health outcomes are also very important. Minor cognitive abnormalities are common, the frequency of depression is increased, and the frequency of hypertension is increased. Careful long-term follow-up of TTP patients is essential.

scholarly journals Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura

Blood ◽  
2013 ◽  
Vol 122 (12) ◽  
pp. 2023-2029 ◽  
Author(s):  
Cassandra C. Deford ◽  
Jessica A. Reese ◽  
Lauren H. Schwartz ◽  
Jedidiah J. Perdue ◽  
Johanna A. Kremer Hovinga ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Complete Recovery ◽  
Systemic Lupus ◽  
Thrombocytopenic Purpura ◽  
Risk Of Death ◽  
Chronic Disorder ◽  
Key Points ◽  
Long Term Follow Up

Key Points After recovering from TTP, the prevalence of hypertension, depression, and systemic lupus erythematosus and risk of death are increased. TTP may be a more chronic disorder rather than a disorder of acute episodes and complete recovery.

Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura

Blood ◽  
2014 ◽  
Vol 124 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Miguel Hie ◽  
Julie Gay ◽  
Lionel Galicier ◽  
François Provôt ◽  
Claire Presne ◽  
...  
Keyword(s):  
High Risk ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Relapse Rate ◽  
Thrombocytopenic Purpura ◽  
Key Points ◽  
History Of ◽  
Adamts13 Deficiency ◽  
Risk Of Relapse

Key Points Patients with a history of acquired TTP and persistent severe ADAMTS13 deficiency during remission are at high risk of relapse and death. Preemptive infusions of rituximab in remission significantly decrease TTP relapse rate.

The Oklahoma thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome Registry

2013 ◽  
Vol 33 (02) ◽  
pp. 105-112 ◽  
Author(s):  
S. K. Vesely ◽  
D. R. Terrell ◽  
C. C. Deford ◽  
J. A. Reese ◽  
Z. L. Al-Nouri ◽  
...  
Keyword(s):  
Patient Care ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Haemolytic Uraemic Syndrome ◽  
Registry Data ◽  
Thrombocytopenic Purpura ◽  
Research Education ◽  
Long Term Follow Up ◽  
And Function

SummaryThe Oklahoma Thrombotic Thrombocytopenic Purpura-Haemolytic Uraemic Syndrome (TTPHUS) Registry has a 24 year record of success for collaborative clinical research, education, and patient care. This article tells the story of how the Registry began and it describes the Registry’s structure and function. The Registry provides a model for using a cohort of consecutive patients to investigate a rare disorder. Collaboration between Oklahoma, United States and Bern, Switzerland has been the basis for successful interpretation of Registry data.Registry data have provided new insights into the evaluation and management of TTP. Because recovery from acute episodes of TTP has been assumed to be complete, the increased prevalence of hypertension, diabetes, depression, and death documented by long-term follow-up was unexpected. Registry data have provided opportunities for projects for students and trainees, education of physicians and nurses, and also for patients themselves. During our follow-up, patients have also educated Registry investigators about problems that persist after recovery from an acute episode of TTP. Most important, Registry data have resulted in important improvements for patient care.

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 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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