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Ugeskrift For Laeger Oct 2021Distinguishing thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies requires measurement of ADAMTS13 enzyme activity, but treatment must... (Review)
Review
Distinguishing thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies requires measurement of ADAMTS13 enzyme activity, but treatment must often be commenced before results from the ADAMTS13 analysis is available. Scoring systems to facilitate prediction of severe ADAMTS13 deficiency and therefore immediate clinical management have been developed. This combined with advances in treatment and monitoring holds optimism for improvements in late effects and survival in future patients. In this review, we discuss status in diagnosing, managing, and follow-up of patients with TTP.
Topics: ADAMTS13 Protein; Humans; Hyperplasia; Optimism; Protein-Energy Malnutrition; Purpura, Thrombotic Thrombocytopenic
PubMed: 34709162
DOI: No ID Found -
Romanian Journal of Internal Medicine =... Dec 2019Immune thrombocytopenia is an autoimmune hematological disorder characterized by severely decreased platelet count of peripheral cause: platelet destruction via... (Review)
Review
Immune thrombocytopenia is an autoimmune hematological disorder characterized by severely decreased platelet count of peripheral cause: platelet destruction via antiplatelet antibodies which may also affect marrow megakaryocytes. Patients may present in critical situations, with cutaneous and/or mucous bleeding and possibly life-threatening organ hemorrhages (cerebral, digestive, etc.) Therefore, rapid diagnosis and therapeutic intervention are mandatory. Corticotherapy represents the first treatment option, but as in any autoimmune disorder, there is a high risk of relapse. Second line therapy options include: intravenous immunoglobulins, thrombopoietin receptor agonists, rituximab or immunosuppression, but their benefit is usually temporary. Moreover, the disease generally affects young people who need repeated and prolonged treatment and hospitalization and therefore, it is preferred to choose a long term effect therapy. Splenectomy - removal of the site of platelet destruction - represents an effective and stable treatment, with 70-80% response rate and low complications incidence. A challenging situation is the association of ITP with pregnancy, which further increases the risk due to the immunodeficiency of pregnancy, major dangers of bleeding, vital risks for mother and fetus, potential risks of medication, necessity of prompt intervention in the setting of specific obstetrical situations - delivery, pregnancy loss, obstetrical complications, etc. We present an updated review of the current clinical and laboratory data, as well as a detailed analysis of the available therapeutic options with their benefits and risks, and also particular associations (pregnancy, relapsed and refractory disease, emergency treatment).
Topics: Diagnosis, Differential; Emergency Treatment; Female; Humans; Pregnancy; Pregnancy Complications; Purpura, Thrombocytopenic, Idiopathic
PubMed: 31199777
DOI: 10.2478/rjim-2019-0014 -
Advances in Chronic Kidney Disease Mar 2022Thrombotic microangiopathies (TMAs) have in common a terminal phenotype of microangiopathic hemolytic anemia with end-organ dysfunction. Thrombotic thrombocytopenic... (Review)
Review
Thrombotic microangiopathies (TMAs) have in common a terminal phenotype of microangiopathic hemolytic anemia with end-organ dysfunction. Thrombotic thrombocytopenic purpura results from von Willebrand factor multimerization, Shiga toxin-mediated hemolytic uremic syndrome causes toxin-induced endothelial dysfunction, while atypical hemolytic uremic syndrome results from complement system dysregulation. Drug-induced TMA, rheumatological disease-induced TMA, and renal-limited TMA exist in an intermediate space that represents secondary complement activation and may overlap with atypical hemolytic uremic syndrome clinically. The existence of TMA without microangiopathic hemolytic features, renal-limited TMA, represents an undiscovered syndrome that responds incompletely and inconsistently to complement blockade. Hematopoietic stem cell transplant-TMA represents another more resistant form of TMA with different therapeutic needs and clinical course. It has become apparent that TMA syndromes are an emerging field in nephrology, rheumatology, and hematology. Much work remains in genetics, molecular biology, and therapeutics to unravel the puzzle of the relationships and distinctions apparent between the different subclasses of TMA syndromes.
Topics: Atypical Hemolytic Uremic Syndrome; Complement System Proteins; Humans; Purpura, Thrombotic Thrombocytopenic; Shiga Toxin; Thrombotic Microangiopathies
PubMed: 35817522
DOI: 10.1053/j.ackd.2021.11.006 -
Blood Reviews Sep 2023There are not many publications that provide a holistic view of the management of primary and secondary ITP as a whole, reflecting the similarities and differences... (Review)
Review
There are not many publications that provide a holistic view of the management of primary and secondary ITP as a whole, reflecting the similarities and differences between the two. Given the lack of major clinical trials, we believe that comprehensive reviews are much needed to guide the diagnosis and treatment of ITP today. Therefore, our review addresses the contemporary diagnosis and treatment of ITP in adult patients. With respect to primary ITP we especially focus on establishing the management of ITP based on the different and successive lines of treatment. Life-threatening situations, "bridge therapy" to surgery or invasive procedures and refractory ITP are also comprehensively reviewed here. Secondary ITP is studied according to its pathogenesis by establishing three major differential groups: Immune Thrombocytopenia due to Central Defects, Immune Thrombocytopenia due to Blocked Differentiation and Immune Thrombocytopenia due to Defective Peripheral Immune Response. Here we provide an up-to-date snapshot of the current diagnosis and treatment of ITP, including a special interest in addressing rare causes of this disease in our daily clinical practice. The target population of this review is adult patients only and the target audience is medical professionals.
Topics: Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Platelet Count; Receptors, Thrombopoietin; Thrombopoietin
PubMed: 37414719
DOI: 10.1016/j.blre.2023.101112 -
Blood Aug 2022Immune-mediated thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy characterized by an acquired ADAMTS13 deficiency as a result of the presence of an... (Review)
Review
Immune-mediated thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy characterized by an acquired ADAMTS13 deficiency as a result of the presence of an antibody inhibitor of ADAMTS13 leading to the formation of ultralarge von Willebrand multimers. Treatment of iTTP includes plasma exchange, high-dose glucocorticoids, rituximab, and, more recently, caplacizumab, to prevent the development of exacerbations. There is the risk of both relapse and long-term complications that include neurocognitive deficits and cardiovascular events that occur in patients in remission after recovery from an acute iTTP episode. Data on the risk factors for the development of these complications, the appropriate screening, and treatment are limited due to the paucity of research. This article is a review of the current understanding on the risk factors for exacerbation, relapse, and long-term complications of iTTP and discusses an approach to observing patients with iTTP after hospital discharge and during the long-term follow-up in the outpatient setting.
Topics: ADAMTS13 Protein; Hospitals; Humans; Patient Discharge; Plasma Exchange; Purpura, Thrombocytopenic, Idiopathic; Purpura, Thrombotic Thrombocytopenic; Recurrence
PubMed: 35667044
DOI: 10.1182/blood.2021014514 -
Blood Reviews Sep 2021Immune thrombocytopenia (ITP), resulting from antibody-mediated platelet destruction combined with impaired platelet production, is a rare cause of thrombocytopenia in... (Review)
Review
Immune thrombocytopenia (ITP), resulting from antibody-mediated platelet destruction combined with impaired platelet production, is a rare cause of thrombocytopenia in both children and adults. The decision to treat newly diagnosed patients is based on several factors, including the desire to increase platelet count to prevent bleeding, induce remission, and improve health-related quality of life (HRQoL). At present, standard first-line therapy is corticosteroids. While this treatment does increase the platelet count in many patients, a high percentage still relapse after discontinuation of therapy. For this reason, alteration or intensification of first-line therapy that results in superior long-term remission rates is desirable. The objective of this review is to outline different upfront strategies for newly diagnosed patients with ITP in an effort to potentially enhance remission rates and prevent relapse, taking into account an assessment of the risks and benefits of each approach. We primarily focus on adults with ITP, highlighting pediatric data and practice when applicable.
Topics: Disease Management; Genetic Variation; Humans; Prognosis; Purpura, Thrombocytopenic, Idiopathic
PubMed: 33736875
DOI: 10.1016/j.blre.2021.100822 -
Arthritis & Rheumatology (Hoboken, N.J.) Feb 2024Thrombotic microangiopathy (TMA) refers to a diverse group of diseases that share clinical and histopathologic features. TMA is clinically characterized by... (Review)
Review
Thrombotic microangiopathy (TMA) refers to a diverse group of diseases that share clinical and histopathologic features. TMA is clinically characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and organ injury that stems from endothelial damage and vascular occlusion. There are several disease states with distinct pathophysiological mechanisms that manifest as TMA. These conditions are associated with significant morbidity and mortality and require urgent recognition and treatment. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are traditionally considered to be primary forms of TMA, but TMA more commonly occurs in association with a coexisting condition such as infection, pregnancy, autoimmune disease, or malignant hypertension, among others. Determining the cause of TMA is a diagnostic challenge because of limited availability of disease-specific testing. However, identifying the underlying etiology is imperative as treatment strategies differ. Our understanding of the conditions that cause TMA is evolving. Recent advances have led to improved comprehension of the varying pathogenic mechanisms that drive TMA. Development of targeted therapeutics has resulted in significant improvements in patient outcomes. In this article, we review the pathogenesis and clinical features of the different TMA-causing conditions. We outline a practical approach to diagnosis and management and discuss empiric and disease-specific treatment strategies.
Topics: Pregnancy; Female; Humans; Thrombotic Microangiopathies; Purpura, Thrombotic Thrombocytopenic; Thrombosis; Anemia, Hemolytic; Hypertension, Malignant
PubMed: 37610060
DOI: 10.1002/art.42681 -
The New England Journal of Medicine Aug 2023
Review
Topics: Female; Humans; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Pregnancy Complications, Hematologic
PubMed: 37590449
DOI: 10.1056/NEJMra2214617 -
Medicina Clinica Jun 2022Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized by the development of microangiopathic haemolytic anaemia,...
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized by the development of microangiopathic haemolytic anaemia, thrombocytopenia, and ischaemic organ dysfunction associated with ADAMTS13 levels lower than 10% in most cases. Recently there have been numerous advances in the field of PTT, new, rapid and accessible techniques capable of quantifying ADAMTS13 activity and inhibitors. The massive sequencing systems facilitate the identification of polymorphisms in the ADAMTS13 gene. In addition, new drugs such as caplacizumab have appeared and relapse prevention strategies are being proposed with the use of rituximab. The existence of TTP patient registries allow a deeper understanding of this disease but the great variability in the diagnosis and treatment makes it necessary to elaborate guidelines that homogenize terminology and clinical practice. The recommendations set out in this document were prepared following the AGREE methodology. The research questions were formulated according to the PICO format. A search of the literature published during the last 10 years was carried out. The recommendations were established by consensus among the entire group, specifying the existing strengths and limitations according to the level of evidence obtained. In conclusion, this document contains recommendations on the management, diagnosis, and treatment of TTP with the ultimate objective of developing guidelines based on the evidence published to date that allow healthcare professionals to optimize TTP treatment.
Topics: Diagnosis, Differential; Humans; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Rituximab; Thrombotic Microangiopathies
PubMed: 34266669
DOI: 10.1016/j.medcli.2021.03.040 -
American Journal of Hematology Feb 2021Immune thrombocytopenia (ITP) has a substantial, multifaceted impact on patients' health-related quality of life (HRQoL). Data describing which aspects of ITP physicians...
Immune thrombocytopenia (ITP) has a substantial, multifaceted impact on patients' health-related quality of life (HRQoL). Data describing which aspects of ITP physicians and patients perceive as having the greatest impact are limited. The ITP World Impact Survey (I-WISh) was a cross-sectional survey, including 1507 patients and 472 physicians, to establish the impact of ITP on HRQoL and productivity from patient and physician perspectives. Patients reported that ITP reduced their energy levels (85% of patients), capacity to exercise (77%), and limited their ability to perform daily tasks (75%). Eighty percent of physicians reported that ITP symptoms reduced patient HRQoL, with 66% reporting ITP-related fatigue substantially reduced patient HRQoL. Patients believed ITP had a substantial impact on emotional well-being (49%) and 63% worried their condition would worsen. Because of ITP, 49% of patients had already reduced, or seriously considered reducing their working hours, and 29% had considered terminating their employment. Thirty-six percent of patients employed at the time of the survey felt ITP decreased their work productivity, while 51% of patients with high/very high symptom burden reported that ITP affected their productivity. Note, I-WISh demonstrated substantive impact of ITP on patients' HRQoL both directly for patients and from the viewpoint of their physicians. Patients reported reduced energy levels, expressed fears their condition might worsen, and those who worked experienced reduced productivity. Physicians should be aware not only of platelet counts and bleeding but also the multi-dimensional impact of ITP on patients' lives as an integral component of disease management.
Topics: Cross-Sectional Studies; Female; Hemorrhage; Humans; Male; Purpura, Thrombocytopenic, Idiopathic; Quality of Life
PubMed: 33107998
DOI: 10.1002/ajh.26036