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Blood Advances Nov 2019Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This...
Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.
Topics: Clinical Decision-Making; Combined Modality Therapy; Decision Trees; Disease Management; Humans; Purpura, Thrombocytopenic, Idiopathic; Severity of Illness Index; Treatment Outcome
PubMed: 31770441
DOI: 10.1182/bloodadvances.2019000812 -
Frontiers in Immunology 2021Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune... (Review)
Review
Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. IgAV is the most common form of vasculitis in children; typical symptoms include palpable purpura, arthritis or arthralgia, abdominal pain, and hematuria or proteinuria. Galactose-deficient IgA1 is detected in the tissues of the kidney and skin in patients with IgAV; it forms immune complexes leading to subsequent immune reactions and injuries. This report provides the recent advances in the understanding of environmental factors, genetics, abnormal innate and acquired immunity, and the role of galactose-deficient IgA1 immunocomplexes in the pathogenesis of IgAV.
Topics: Animals; Environment; Humans; IgA Vasculitis
PubMed: 34858429
DOI: 10.3389/fimmu.2021.771619 -
Blood Advances Dec 2019Despite an increase in the number of therapies available to treat patients with immune thrombocytopenia (ITP), there are minimal data from randomized trials to assist...
BACKGROUND
Despite an increase in the number of therapies available to treat patients with immune thrombocytopenia (ITP), there are minimal data from randomized trials to assist physicians with the management of patients.
OBJECTIVE
These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the management of ITP.
METHODS
In 2015, ASH formed a multidisciplinary guideline panel that included 8 adult clinical experts, 5 pediatric clinical experts, 2 methodologists with expertise in ITP, and 2 patient representatives. The panel was balanced to minimize potential bias from conflicts of interest. The panel reviewed the ASH 2011 guideline recommendations and prioritized questions. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including evidence-to-decision frameworks, to appraise evidence (up to May 2017) and formulate recommendations.
RESULTS
The panel agreed on 21 recommendations covering management of ITP in adults and children with newly diagnosed, persistent, and chronic disease refractory to first-line therapy who have non-life-threatening bleeding. Management approaches included: observation, corticosteroids, IV immunoglobulin, anti-D immunoglobulin, rituximab, splenectomy, and thrombopoietin receptor agonists.
CONCLUSIONS
There was a lack of evidence to support strong recommendations for various management approaches. In general, strategies that avoided medication side effects were favored. A large focus was placed on shared decision-making, especially with regard to second-line therapy. Future research should apply standard corticosteroid-dosing regimens, report patient-reported outcomes, and include cost-analysis evaluations.
Topics: Hematology; History, 21st Century; Humans; Purpura, Thrombocytopenic, Idiopathic; United States
PubMed: 31794604
DOI: 10.1182/bloodadvances.2019000966 -
Journal of Thrombosis and Haemostasis :... Oct 2020Despite advances in treatment options for thrombotic thrombocytopenic purpura (TTP), there are still limited high quality data to inform clinicians regarding its...
BACKGROUND
Despite advances in treatment options for thrombotic thrombocytopenic purpura (TTP), there are still limited high quality data to inform clinicians regarding its appropriate treatment.
METHODS
In June 2018, the ISTH formed a multidisciplinary guideline panel to issue recommendations about treatment of TTP. The panel discussed 12 treatment questions related to immune-mediated TTP (iTTP) and hereditary or congenital TTP (cTTP). The panel used the Grading of Recommendations Assessment, Development, and Evaluation approach, including evidence-to-decision frameworks, to appraise evidence and formulate recommendations.
RESULTS
The panel agreed on 11 recommendations based on evidence ranging from very low to moderate certainty. For first acute episode and relapses of iTTP, the panel made a strong recommendation for adding corticosteroids to therapeutic plasma exchange (TPE) and a conditional recommendation for adding rituximab and caplacizumab. For asymptomatic iTTP with low plasma ADAMTS13 activity, the panel made a conditional recommendation for the use of rituximab outside of pregnancy, but prophylactic TPE during pregnancy. For asymptomatic cTTP, the panel made a strong recommendation for prophylactic plasma infusion during pregnancy, and a conditional recommendation for plasma infusion or a wait and watch approach outside of pregnancy.
CONCLUSIONS
The panel's recommendations are based on all the available evidence for the effects of an individual component of various treatment approaches, including suppressing inflammation, blocking platelet clumping, replacing the missing and/or inhibited ADAMTS13, and suppressing the formation of ADAMTS13 autoantibody. There was insufficient evidence for further comparing different treatment approaches (eg, TPE, corticosteroids, rituximab, and caplacizumab, etc.), for which high quality studies are needed.
Topics: ADAMTS13 Protein; Autoantibodies; Humans; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Rituximab; Single-Domain Antibodies
PubMed: 32914526
DOI: 10.1111/jth.15010 -
Journal of Hematology & Oncology Jan 2023Primary immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder characterized by decreased platelet counts and an increased risk of bleeding. Multiple... (Review)
Review
Primary immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder characterized by decreased platelet counts and an increased risk of bleeding. Multiple humoral and cellular immune abnormalities result in accelerated platelet destruction and suppressed platelet production in ITP. The diagnosis remains a clinical exclusion of other causes of thrombocytopenia. Treatment is not required except for patients with active bleeding, severe thrombocytopenia, or cases in need of invasive procedures. Corticosteroids, intravenous immunoglobulin, and anti-RhD immunoglobulin are the classical initial treatments for newly diagnosed ITP in adults, but these agents generally cannot induce a long-term response in most patients. Subsequent treatments for patients who fail the initial therapy include thrombopoietic agents, rituximab, fostamatinib, splenectomy, and several older immunosuppressive agents. Other potential therapeutic agents, such as inhibitors of Bruton's tyrosine kinase and neonatal Fc receptor, are currently under clinical evaluation. An optimized treatment strategy should aim at elevating the platelet counts to a safety level with minimal toxicity and improving patient health-related quality of life, and always needs to be tailored to the patients and disease phases. In this review, we address the concepts of adult ITP diagnosis and management and provide a comprehensive overview of current therapeutic strategies under general and specific situations.
Topics: Adult; Humans; Blood Platelets; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Thrombocytopenia
PubMed: 36658588
DOI: 10.1186/s13045-023-01401-z -
Hematology. American Society of... Dec 2022Hematologists are often consulted for thrombocytopenia in pregnancy, especially when there is a concern for a non-pregnancy-specific etiology or an insufficient platelet... (Review)
Review
Hematologists are often consulted for thrombocytopenia in pregnancy, especially when there is a concern for a non-pregnancy-specific etiology or an insufficient platelet count for the hemostatic challenges of delivery. The severity of thrombocytopenia and trimester of onset can help guide the differential diagnosis. Hematologists need to be aware of the typical signs of preeclampsia with severe features and other hypertensive disorders of pregnancy to help distinguish these conditions, which typically resolve with delivery, from other thrombotic microangiopathies (TMAs) (eg, thrombotic thrombocytopenic purpura or complement-mediated TMA). Patients with chronic thrombocytopenic conditions, such as immune thrombocytopenia, should receive counseling on the safety and efficacy of various medications during pregnancy. The management of pregnant patients with chronic immune thrombocytopenia who are refractory to first-line treatments is an area that warrants further research. This review uses a case-based approach to discuss recent updates in diagnosing and managing thrombocytopenia in pregnancy.
Topics: Female; Pregnancy; Humans; Purpura, Thrombocytopenic, Idiopathic; Pregnancy Complications, Hematologic; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Platelet Count
PubMed: 36485110
DOI: 10.1182/hematology.2022000375 -
Blood Feb 2020Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia after chemotherapy-induced thrombocytopenia. Existing guidelines describe the management and... (Review)
Review
Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia after chemotherapy-induced thrombocytopenia. Existing guidelines describe the management and treatment of most patients who, overall, do well, even if they present with chronic disease, and they are usually not at a high risk for bleeding; however, a small percentage of patients is refractory and difficult to manage. Patients classified as refractory have a diagnosis that is not really ITP or have disease that is difficult to manage. ITP is a diagnosis of exclusion; no specific tests exist to confirm the diagnosis. Response to treatment is the only affirmative confirmation of diagnosis. However, refractory patients do not respond to front-line or other treatments; thus, no confirmation of diagnosis exists. The first section of this review carefully evaluates the diagnostic considerations in patients with refractory ITP. The second section describes combination treatment for refractory cases of ITP. The reported combinations are divided into the era before thrombopoietin (TPO) and rituximab and the current era. Current therapy appears to have increased effectiveness. However, the definition of refractory, if it includes insufficient response to TPO agents, describes a group with more severe and difficult-to-treat disease. The biology of refractory ITP is largely unexplored and includes oligoclonality, lymphocyte pumps, and other possibilities. Newer treatments, especially rapamycin, fostamatinib, FcRn, and BTK inhibitors, may be useful components of future therapy given their mechanisms of action; however, TPO agents, notwithstanding failure as monotherapy, appear to be critical components. In summary, refractory ITP is a complicated entity in which a precise specific diagnosis is as important as the development of effective combination treatments.
Topics: Clinical Trials as Topic; Diagnosis, Differential; Drug Therapy, Combination; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
PubMed: 31756253
DOI: 10.1182/blood.2019003599 -
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 -
Zeitschrift Fur Rheumatologie May 2022Immunoglobulin A vasculitis (IgAV) is a systemic vasculitis of the small vessels with formation of IgA immune complexes and a broad spectrum of clinical... (Review)
Review
Immunoglobulin A vasculitis (IgAV) is a systemic vasculitis of the small vessels with formation of IgA immune complexes and a broad spectrum of clinical constellations. Typical manifestations include purpura, arthralgia or arthritis, enteritis and glomerulonephritis. The IgAV is the most common vasculitis in childhood with a mostly uncomplicated and self-limiting course. In adults IgAV is much less frequent but the course can be more complicated, especially with renal or gastrointestinal manifestations. Various triggers of IgAV including infections have been described, whereby impaired glycosylation of IgA1 with subsequent exposure of binding sites for autoantibodies is a pathophysiological precondition for the vasculitis. Therapeutic strategies with immunosuppressants are so far supported by low evidence, take the severity of the organ manifestations into account and are oriented towards the recommendations for the treatment of other vasculitides of small vessels. Benign courses are treated symptomatically. The long-term prognosis of IgAV is determined by the renal manifestation.
Topics: Adult; Female; Glomerulonephritis; Humans; IgA Vasculitis; Immunoglobulin A; Kidney; Male; Vasculitis
PubMed: 35303751
DOI: 10.1007/s00393-022-01162-z -
Journal of Thrombosis and Haemostasis :... Oct 2020Despite an increase in our understandings of pathogenesis of thrombotic thrombocytopenic purpura (TTP), the approaches for initial diagnosis and management of TTP vary...
BACKGROUND
Despite an increase in our understandings of pathogenesis of thrombotic thrombocytopenic purpura (TTP), the approaches for initial diagnosis and management of TTP vary significantly.
OBJECTIVE
The evidence-based guidelines of the International Society on Thrombosis and Haemostasis (ISTH) are intended to support patients, clinicians, and other health care professionals in their decisions about the initial diagnosis and management of acute TTP.
METHODS
In June 2018, ISTH formed a multidisciplinary panel that included hematologists, an intensive care physician, nephrologist, clinical pathologist, biostatistician, and patient representatives, as well as a methodology team from McMaster University. The panel composition was designed to minimize the potential conflicts of interests. The panel used the Grading of Recommendations Assessment, Development, and Evaluation approach and the Population, Intervention, Comparison, Outcome framework to develop and grade their recommendations. Public comments were sought and incorporated in the final document.
RESULTS
The panel agreed on three recommendations covering the initial diagnosis with emphasis on the importance of ADAMTS13 testing (eg, activity, anti-ADAMTS13 IgG or inhibitor) and assessment of the pretest probability of TTP by clinical assessment and/or the risk assessment models like the PLASMIC or French score. The panel noted how availability and turnaround time of ADAMTS13 test results might affect early diagnosis and management, in particular the use of caplacizumab.
CONCLUSIONS
There is a lack of high-quality evidence to support strong recommendations for the initial diagnosis and management of a suspected TTP. The panel emphasized the importance of obtaining ADAMTS13 testing in a proper clinical context. Future research should focus on how to monitor and act on ADAMTS13 levels during remission.
Topics: ADAMTS13 Protein; Early Diagnosis; Hemostasis; Humans; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Thrombosis
PubMed: 32914582
DOI: 10.1111/jth.15006