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Hematology. American Society of... Nov 2018Immune thrombocytopenia (ITP) has historically been thought to occur in 2 distinct forms: childhood ITP and adult ITP. This division is based largely on the presumption... (Review)
Review
Immune thrombocytopenia (ITP) has historically been thought to occur in 2 distinct forms: childhood ITP and adult ITP. This division is based largely on the presumption that childhood ITP is often benign and self-limited, whereas ITP in adults tends to be more chronic and difficult to treat. Although data exist to justify a different approach to the diagnosis and treatment in young children and the elderly, ITP in older children, adolescents, and younger adults is likely to share more similar pathology. This article will highlight the most recent data describing the natural history, diagnostic approach, management strategies, and disease-related outcomes in children and adults with ITP. These data reveal many unexpected similarities between the 2 groups, while confirming some of the more well-described differences. Discussion of these findings aims to highlight similarities and differences between ITP in children and adults, which will underscore important areas of future research and/or changes in management guidelines.
Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Humans; Infant; Practice Guidelines as Topic; Purpura, Thrombocytopenic, Idiopathic
PubMed: 30504339
DOI: 10.1182/asheducation-2018.1.405 -
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 -
Medicina (Kaunas, Lithuania) Nov 2020Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia caused by increased platelet destruction and impaired... (Review)
Review
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia caused by increased platelet destruction and impaired platelet production. First-line therapies include corticosteroids, intravenous immunoglobulin, and anti-D immunoglobulin. For patients who are refractory to these therapies, those who become corticosteroid dependent, or relapse following treatment with corticosteroid, options include splenectomy, rituximab, and thrombopoietin-receptor agonists, alongside a variety of additional immunosuppressive and experimental therapies. Despite recent advances in the management of ITP, many areas need further research. Although it is recognized that an assessment of patient-reported outcomes in ITP is valuable to understand and guide treatment, these measures are not routinely measured in the clinical setting. Consequently, although corticosteroids are first-line therapies for both children and adults, there are no data to suggest that corticosteroids improve health-related quality of life or other patient-related outcomes in either children or adults. In fact, long courses of corticosteroids, in either children or adults, may have a negative impact on a patient's health-related quality of life, secondary to the impact on sleep disturbance, weight gain, and mental health. In adults, additional therapies may be needed to treat overt hemorrhage, but unfortunately the results are transient for the majority of patients. Therefore, there is a need to recognize the limitations of current existing therapies and evaluate new approaches, such as individualized treatment based on the probability of response and the size of effect on the patient's most bothersome symptoms and risk of adverse effects or complications. Finally, a validated screening tool that identifies clinically significant patient-reported outcomes in routine clinical practice would help both patients and physicians to effectively follow a patient's health beyond simply treating the laboratory findings and physical symptoms of ITP. The goal of this narrative review is to discuss management of newly diagnosed and refractory patients with ITP, with a focus on the limitations of current therapies from the patient's perspective.
Topics: Adult; Child; Humans; Neoplasm Recurrence, Local; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Splenectomy; Thrombocytopenia
PubMed: 33266286
DOI: 10.3390/medicina56120667 -
Clinical Interventions in Aging 2023Many epidemiological studies have shown that the incidence of immune thrombocytopenia (ITP) increases after age 60 years and peaks in patients over age 80 years.... (Review)
Review
Many epidemiological studies have shown that the incidence of immune thrombocytopenia (ITP) increases after age 60 years and peaks in patients over age 80 years. Therefore, ITP is a concern for physicians taking care of older patients, especially regarding its diagnosis and management. The diagnostic work-up should exclude other causes of thrombocytopenia and secondary ITP, including myelodysplastic syndrome and drug-induced ITP. The treatment decision is influenced by an increased risk of bleeding, infectious diseases and thrombosis in this population and should take into account comorbidities and concomitant medications such as anticoagulant drugs. First-line treatment is based on short corticosteroids courses and intravenous immunoglobulin, which should be reserved for patients with more severe bleeding complications, with their higher risk of toxic effects as compared with younger patients. Second-line treatment should be tailored to the patient's history, comorbidities and preferences. Preferred second-line treatments are thrombopoietin receptor agonists for most groups and guidelines given their good efficacy/tolerance ratio, but the thrombotic risk is increased in older people. Other second-line options that can be good alternatives depending on the clinical context include rituximab, dapsone, fostamatinib or immunosuppressive drugs. Splenectomy is less often performed but remains an option for fit patients with chronic refractory disease. Emerging treatments such as Syk or Bruton tyrosine kinase inhibitors and FcRn antagonists are becoming available for ITP and may modify the treatment algorithm in the near future. The aim of this review is to describe the particularities of the diagnosis and treatment of ITP in older people, including the response and tolerance to the currently available drugs. We also discuss some situations related to co-morbidities that can frequently lead to adapt the management strategy in older patients.
Topics: Aged; Aged, 80 and over; Humans; Glucocorticoids; Immunoglobulins, Intravenous; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Thrombocytopenia
PubMed: 36726813
DOI: 10.2147/CIA.S369574 -
Hematology. American Society of... Nov 2018Thrombotic thrombocytopenia purpura (TTP) is a rare, life-threatening disease with an incidence of approximately 2 persons per million per year. It is characterized by... (Review)
Review
Thrombotic thrombocytopenia purpura (TTP) is a rare, life-threatening disease with an incidence of approximately 2 persons per million per year. It is characterized by severe deficiency of the von Willebrand cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), leading to formation of platelet-rich thrombi in the microvasculature. Prompt initiation of appropriate therapy, particularly plasma exchange, may be life-saving. Diagnosis of TTP is challenging because of its diverse clinical manifestations, overlap in clinical presentation with other thrombotic microangiopathies, and limited availability of ADAMTS13 testing. Clinical prediction scores have been developed to estimate the pretest probability of severe ADAMTS13 deficiency and may be used as an adjunct to clinical judgment to guide initial management decisions. An ADAMTS13 activity level of less than 10% supports the diagnosis of TTP in appropriate clinical contexts, but many centers do not offer testing in-house and must send out the test to a reference laboratory with a turnaround time of several days. In such instances, initial management decisions must be made without the benefit of laboratory testing. In patients with TTP, inhibitor tests may be useful for distinguishing immune-mediated from congenital TTP. In this article, we review the epidemiology, natural history, and clinical presentation of TTP and laboratory assays for TTP including ADAMTS13 activity and inhibitor assays. We also describe an evidence-based approach to the evaluation of a patient with suspected TTP that integrates clinical and laboratory assessment.
Topics: ADAMTS13 Protein; Clinical Laboratory Techniques; Humans; Purpura, Thrombotic Thrombocytopenic
PubMed: 30504354
DOI: 10.1182/asheducation-2018.1.530 -
British Journal of Haematology Nov 2018
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Thiazoles; Thiophenes
PubMed: 30351482
DOI: 10.1111/bjh.15568 -
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 -
Anales de Pediatria Aug 2019Primary immune thrombocytopenia, formerly known as immune thrombocytopenic purpura, is a disease for which the clinical and therapeutic management has always been...
Primary immune thrombocytopenia, formerly known as immune thrombocytopenic purpura, is a disease for which the clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of primary immune thrombocytopenia in children, based on current guidelines, bibliographic review, clinical assays, and member consensus. The main objective is to reduce clinical variability in diagnostic and therapeutic procedures, in order to obtain best clinical results with minimal adverse events and good quality of life.
Topics: Child; Humans; Purpura, Thrombocytopenic, Idiopathic; Quality of Life
PubMed: 31178291
DOI: 10.1016/j.anpedi.2019.04.014 -
Blood Aug 2022Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia in children and is caused by immune-mediated decreased platelet production and increased...
Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia in children and is caused by immune-mediated decreased platelet production and increased platelet destruction. In the absence of a diagnostic test, ITP must be differentiated from other thrombocytopenic disorders, including inherited platelet disorders. In addition, a diagnosis of secondary ITP due to a primary immune deficiency with immune dysregulation may not be apparent at diagnosis but can alter management and should be considered in an expanding number of clinical scenarios. The diagnostic evaluation of children with thrombocytopenia will vary based on the clinical history and laboratory features. Access to genotyping has broadened the ability to specify the etiology of thrombocytopenia, whereas increasing access to immunophenotyping, functional immunologic and platelet assays, and biochemical markers has allowed for more in-depth evaluation of patients. With this greater availability of testing, diagnostic algorithms in patients with thrombocytopenia have become complex. In this article, we highlight the diagnostic evaluation of thrombocytopenia in children with a focus on ITP, including consideration of underlying genetic and immune disorders, and use hypothetical patient cases to describe disease manifestations and strategies for treatment of pediatric ITP.
Topics: Biomarkers; Blood Platelets; Child; Humans; Leukopenia; Neuroblastoma; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
PubMed: 34479363
DOI: 10.1182/blood.2020006480 -
Journal of Thrombosis and Haemostasis :... Mar 2023The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data...
BACKGROUND
The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety.
OBJECTIVES
This study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting.
METHODS
We report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls).
RESULTS
Caplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%.
CONCLUSION
Caplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www.
CLINICALTRIALS
gov as #NCT04985318.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Single-Domain Antibodies; Purpura, Thrombocytopenic, Idiopathic; Treatment Outcome; Thrombosis; ADAMTS13 Protein
PubMed: 36696206
DOI: 10.1016/j.jtha.2022.11.010