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1
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Săsăran MO, Mărginean CO, Koller AM. Impact of Helicobacter pylori Infection upon the Evolution and Outcome of Pediatric Immune Thrombocytopenic Purpura: A Comprehensive Review. Diagnostics (Basel) 2023; 13:3205. [PMID: 37892026 PMCID: PMC10606204 DOI: 10.3390/diagnostics13203205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/08/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
In adults with immune thrombocytopenic purpura (ITP), the identification of H. pylori infection and its subsequent eradication proved to aid platelet recovery. Similar findings, at a smaller scale, were allegedly reported by some pediatric studies. This review's objective was to establish the influence of H. pylori infection and its eradication upon platelet count and recovery in pediatric ITP. Three databases, namely Pubmed, Scopus and Web of Science, were searched for pediatric studies which investigated a link between H. pylori infection and thrombocytopenia. The search results retrieved a number of 21 articles which complied to the inclusion and exclusion criteria. Some studies report lower platelet values among children with ITP and documented H. pylori infection, as well as an improve in platelet numbers after H. pylori treatment. However, results are controversial, as multiple authors failed to identify a higher prevalence of H. pylori among children with ITP or a lack of significant change in therapeutic outcome with the addition of an eradication regimen to standard treatment. The main limitations of current pediatric studies remain the small study samples and the short follow-up periods of the included subjects. Hence, the long-term impact of H. pylori in children with ITP is still uncertain.
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Affiliation(s)
- Maria Oana Săsăran
- Department of Pediatrics 3, University of Medicine, Pharmacy, Sciences and Technology George Emil Palade from Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania;
| | - Cristina Oana Mărginean
- Department of Pediatrics 1, University of Medicine, Pharmacy, Sciences and Technology George Emil Palade from Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
| | - Ana Maria Koller
- Clinics of Pediatrics, Emergency County Clinical Hospital, Gheorghe Marinescu Street No. 50, 540136 Târgu Mureș, Romania;
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2
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Young CC, LaRovere KL, Newhams MM, Kucukak S, Gertz SJ, Maddux AB, Halasa NB, Crandall H, Kong M, Fitzgerald JC, Irby K, Randolph AG, Campbell AP, Son MBF. Clinical Course Associated with Aseptic Meningitis Induced by Intravenous Immunoglobulin for the Treatment of Multisystem Inflammatory Syndrome in Children. J Pediatr 2023:113372. [PMID: 36870559 DOI: 10.1016/j.jpeds.2023.01.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 12/15/2022] [Accepted: 01/11/2023] [Indexed: 03/06/2023]
Abstract
Aseptic meningitis is a rare but potentially serious complication of intravenous immunoglobulin (IVIG) treatment. In this case series, meningitic symptoms following IVIG initiation in patients with multisystem inflammatory syndrome were rare (7/2,086 [0.3%]). However, they required the need for additional therapy and/or readmission.
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Affiliation(s)
- Cameron C Young
- Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital, Boston, MA, USA
| | - Kerri L LaRovere
- Department of Neurology, Boston Children's Hospital, Boston, MA, USA
| | - Margaret M Newhams
- Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital, Boston, MA, USA
| | - Suden Kucukak
- Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital, Boston, MA, USA
| | - Shira J Gertz
- Division of Pediatric Critical Care, Department of Pediatrics, Cooperman Barnabas Medical Center, Livingston, NJ, USA
| | - Aline B Maddux
- Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA
| | - Natasha B Halasa
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Hillary Crandall
- Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
| | - Michele Kong
- Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Julie C Fitzgerald
- Division of Critical Care, Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Katherine Irby
- Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock, AR, USA
| | - Adrienne G Randolph
- Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital, Boston, MA, USA; Departments of Anaesthesia and Pediatrics, Harvard Medical School, Boston MA, USA
| | - Angela P Campbell
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Mary Beth F Son
- Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
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3
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Harris EM, Hillier K, Nolan M, Meleedy-Rey P, Buissereth T, Grace RF. Utilization of an ITP quality improvement pathway improves adherence to management guidelines. Pediatr Blood Cancer 2023; 70:e30074. [PMID: 36518083 DOI: 10.1002/pbc.30074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 09/10/2022] [Accepted: 09/26/2022] [Indexed: 12/23/2022]
Abstract
Despite availability of epidemiologic studies and national guidelines for the management of newly diagnosed pediatric immune thrombocytopenia (ITP), practice variation exists among and within hematology practices. We previously described the development of an ITP pathway guiding management based on bleeding symptoms. Over an 8-year period, integration of this iterative ITP pathway into management of newly diagnosed ITP increased observation rates in children with no or mild bleeding symptoms and improved consistency of laboratory evaluation and treatment strategies without increasing adverse outcomes. This quality improvement initiative has been sustainable, acceptable to providers, and increased adherence to guidelines.
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Affiliation(s)
- Emily M Harris
- Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Kirsty Hillier
- Department of Pediatrics, Division of Pediatric Hematology-Oncology, Hassenfeld Children's Hospital at NYU Langone Health, NYU Grossman School of Medicine, New York, New York, USA
| | - Michaela Nolan
- Program for Patient Safety and Quality, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Patricia Meleedy-Rey
- Program for Patient Safety and Quality, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Taylah Buissereth
- Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Rachael F Grace
- Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA
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4
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Visweshwar N, Ayala I, Jaglal M, Killeen R, Sokol L, Laber DA, Manoharan A. Primary immune thrombocytopenia: a 'diagnosis of exclusion'? Blood Coagul Fibrinolysis 2022; 33:289-294. [PMID: 35867940 PMCID: PMC9415225 DOI: 10.1097/mbc.0000000000001144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 04/21/2022] [Accepted: 04/26/2022] [Indexed: 01/19/2023]
Abstract
Current diagnosis of primary immune thrombocytopenia (ITP) is presumptive, centered on excluding other causes of thrombocytopenia. The diagnosis of ITP is challenging because of the wide range of potential inherited and acquired causes of thrombocytopenia. The treatment of ITP is empiric with steroids, high-dose immunoglobulin, immunosuppressants and thrombopoietin agonists with potential side effects. We searched Medline and Cochrane databases, reviewed the study data and analyzed the individual diagnostic tests for their evidence-based role in the diagnosis of ITP. We then analyzed the strength of the scientific evidence for each diagnostic test in the diagnosis of ITP and identified gaps in the diagnostic accuracy. The diagnostic challenges in ITP include: insufficient evidence for the individual test for diagnosis of ITP, no standardized protocol/guideline for diagnosis, hurdles in accessing the available resources and failure to correlate the clinical data while reviewing the blood smear. We did not identify a diagnostic test that clinicians can use to confirm the diagnosis of ITP. In the absence of a diagnostic test of proven value in ITP, the clinician is best served by a comprehensive history and physical examination, complete blood count and review of the peripheral blood smear in evaluating thrombocytopenia.
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Affiliation(s)
| | - Irmel Ayala
- Division of Hematology, Johns Hopkins All Children's Hospital, St. Petersburg
| | | | | | - Lubomir Sokol
- Department of Malignant Hematology, Moffitt Cancer Center, Tampa, Florida, USA
| | | | - Arumugam Manoharan
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia
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5
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Schifferli A, Heiri A, Imbach P, Holzhauer S, Seidel MG, Nugent D, Michel M, Kühne T. Misdiagnosed thrombocytopenia in children and adolescents: analysis of the Pediatric and Adult Registry on Chronic ITP. Blood Adv 2021; 5:1617-1626. [PMID: 33710335 PMCID: PMC7993109 DOI: 10.1182/bloodadvances.2020003004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 01/23/2021] [Indexed: 02/06/2023] Open
Abstract
Primary immune thrombocytopenia (ITP) in children is a diagnosis of exclusion, but cases of secondary ITP and nonimmune thrombocytopenia (non-IT) are generally difficult to recognize in a timely fashion. We describe a pediatric population with a revised diagnosis of secondary ITP or non-IT within 24 months of follow-up. Data were extracted from the Pediatric and Adult Registry on Chronic ITP, an international multicenter registry collecting data prospectively in patients with newly diagnosed primary ITP. Between 2004 and 2019, a total of 3974 children aged 3 months to 16 years were included. Secondary ITP and non-IT were reported in 113 patients (63 female subjects). Infectious (n = 53) and autoimmune (n = 42) diseases were identified as the main causes, with median ages at diagnosis of 3.2 years (interquartile range: 1.2; 6.7 years) and 12.4 years (interquartile range: 7.6; 13.7 years), respectively. Other causes included malignancies, aplastic anemia, immunodeficiency, and drug use. Patients with malignancy and aplastic anemia had significantly higher initial platelet counts (37 and 52 × 109/L) than did those with infection or autoimmune diseases (12 and 13 × 109/L). Characteristics of patients with secondary ITP due to infection were similar to those of children with primary ITP at first presentation, indicating similar mechanisms. Significant differences were found for age, sex, comorbidities, initial bleeding, sustained need for treatment, and disease persistence for the remaining noninfectious group compared with primary ITP. Based on our findings, we propose a diagnostic algorithm that may serve as a basis for further discussion and prospective trials.
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Affiliation(s)
- Alexandra Schifferli
- Department of Hematology/Oncology, University Children's Hospital Basel, Basel, Switzerland
| | - Andrea Heiri
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Paul Imbach
- Department of Hematology/Oncology, University Children's Hospital Basel, Basel, Switzerland
| | - Susanne Holzhauer
- Department of Pediatric Hematology and Oncology, Charité University Medicine, Berlin, Germany
| | - Markus G Seidel
- Research Unit for Pediatric Hematology and Immunology, Division of Pediatric Hemato-/Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Diane Nugent
- Children's Hospital of Orange County, University of California Irvine, Irvine, CA; and
| | - Marc Michel
- Department of Internal Medicine, National Reference Center for Adult Immune Cytopenias, Henri Mondor University Hospital, Assistance Publique-Hopitaux de Paris, Université Paris-Est Créteil, Créteil, France
| | - Thomas Kühne
- Department of Hematology/Oncology, University Children's Hospital Basel, Basel, Switzerland
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6
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Lassandro G, Palmieri VV, Barone A, Farruggia P, Giona F, Licciardello M, Marinoni M, Marzollo A, Notarangelo LD, Palumbo G, Ramenghi U, Russo G, Saracco P, Spinelli M, Tolva A, Tornesello A, Palladino V, Noviello D, Giordano P. Fatigue perception in a cohort of children with chronic immune thrombocytopenia and their caregivers using the PedsQL MFS: Real-life multicenter experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Pediatr Blood Cancer 2021; 68:e28840. [PMID: 33274837 DOI: 10.1002/pbc.28840] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Fatigue is an important clinical and psychological aspect for a significant number of children affected by immune thrombocytopenia (ITP). To date, few studies have explored fatigue and its relationship with chronic ITP in pediatric age. The aim of the present multicentric pilot study is to determine fatigue perception in a large group of children with chronic ITP and their caregivers using the PedsQL Multidimensional Fatigue Scale (PedsQL MFS), and to compare the results with those of healthy control subjects. PROCEDURE Children with chronic ITP aged 5-18 years and/or caregivers of children aged 2-18 years were enrolled. Child/adolescent self-report was used for patients aged 5-18 years, and parent proxy-report for patients aged 2-18 years. The questionnaire was offered as online survey. PedsQL MFS is composed of 18 items covering three dimensions: General Fatigue Scale, Sleep/Rest Fatigue Scale, and Cognitive Fatigue Scale. RESULTS One hundred ninety-one patients affected by chronic ITP and 248 caregivers answered the PedsQL MFS. We have highlighted that lower values of PedsQL MFS scores are obtained in the 13-18 age group. Moreover, sleep/rest fatigue domain appears to be more compromised in all age groups. For all PedsQL MFS scores, pediatric patients with chronic ITP and their caregivers reported statistically significant worse fatigue than healthy children. CONCLUSIONS This study suggests that fatigue is relevant among children and adolescents affected by chronic ITP. The PedsQL MFS represents an adequate instrument for measuring fatigue in patients with chronic ITP. Therefore, symptoms of fatigue should be routinely assessed in clinical practice.
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Affiliation(s)
- Giuseppe Lassandro
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Viviana Valeria Palmieri
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Angelica Barone
- Department of Pediatric Onco-Hematology, University Hospital of Parma, Parma, Italy
| | - Piero Farruggia
- Pediatric Hematology and Oncology Unit, A.R.N.A.S. Ospedale Civico, Palermo, Italy
| | - Fiorina Giona
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Maria Licciardello
- Pediatric Hemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Maddalena Marinoni
- Paediatric Department, ASST-Sette Laghi, "F. Del Ponte" Hospital, Varese, Italy
| | - Antonio Marzollo
- Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, Azienda Ospedaliera-University of Padova, Padua, Italy
| | | | - Giuseppe Palumbo
- Regional Reference Centre for Haemostasis and Thrombosis, IRCCS Paediatric Hospital "Bambino Gesù,", Rome, Italy
| | - Ugo Ramenghi
- Department of Pediatric and Public Health Sciences, University of Torino, Turin, Italy
| | - Giovanna Russo
- Pediatric Hemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Paola Saracco
- Department of Pediatric and Public Health Sciences, University of Torino, Turin, Italy
| | - Marco Spinelli
- Hemato-Oncology Unit, Fondazione MBBM, San Gerardo Hospital, Monza, Italy
| | - Alessandra Tolva
- Pediatric Hematology/Oncology, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Assunta Tornesello
- Pediatric Hematology Oncology, Presidio Ospedaliero Vito Fazzi, Lecce, Italy
| | - Valentina Palladino
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Domenico Noviello
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Paola Giordano
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
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7
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Lassandro G, Carriero F, Palmieri V, Palladino V, Amoruso A, Gallone MF, Del Vecchio GC, Tafuri S, Russo G, Valente F, Giordano P. Serum Vitamin D Levels in Children with Immune Thrombocytopenia. Endocr Metab Immune Disord Drug Targets 2020; 20:221-226. [PMID: 31203812 DOI: 10.2174/1871530319666190614152709] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 03/20/2019] [Accepted: 03/20/2019] [Indexed: 01/20/2023]
Abstract
OBJECTIVE Immune thrombocytopenia (ITP) is an acquired immuno-mediated disorder characterized by thrombocytopenia with an increased risk of bleeding. In recent years 1,25[OH]2D3 has been rediscovered as an immune modulator. We decided to evaluate serum Vitamin D levels in a cohort of children with immune thrombocytopenia in order to discover if Vitamin D concentrations may predict ITP duration. METHODS Thirty children were enrolled in this study (sixteen with chronic ITP and fourteen with newly diagnosed ITP) to assess serum Vitamin D levels. RESULTS The results showed that 80% of the enrolled children presented a D hypovitaminosis status. Children with newly diagnosis ITP showed no statistically significantly higher median values of Vitamin D compared to chronic ITP. CONCLUSION This study may suggest that Vitamin D deficiency does not represent a chronicity factor for ITP. However, further studies are needed to understand the role of Vitamin D in ITP pathogenesis.
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Affiliation(s)
- Giuseppe Lassandro
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Francesco Carriero
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Viviana Palmieri
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Valentina Palladino
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Anna Amoruso
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Maria Filomena Gallone
- Department of Biomedical Science and Human Oncology, Hygiene Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Giovanni C Del Vecchio
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Silvio Tafuri
- Department of Biomedical Science and Human Oncology, Hygiene Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Giovanna Russo
- Pediatric Hematology and Oncology Unit, Azienda Policlinico-Vittorio Emanuele University of Catania, Catania, Italy
| | - Federica Valente
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Paola Giordano
- Department of Biomedical Science and Human Oncology, Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
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Lassandro G, Palladino V, Vecchio GCD, Palmieri VV, Corallo PC, Faienza MF, Giordano P. Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era. Endocr Metab Immune Disord Drug Targets 2020; 21:397-406. [PMID: 32473624 DOI: 10.2174/1871530320666200531142244] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 04/03/2020] [Accepted: 04/23/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND AND OBJECTIVE Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. The management of ITP in children is controversial, requiring personalized assessment of patients and therapeutic choices. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, have been shown to be safe and effective for the treatment of pediatric ITP. The aim of our research is to define the role of thrombopoietin receptor agonists in the management of pediatric ITP. METHODS This review focuses on the use of TPO-RAs in pediatric ITP, in randomized trials and in clinical routine, highlighting their key role in the management of the disease. RESULTS Eltrombopag and romiplostim appear effective treatment options for children with ITP. Several clinical studies have assessed that the use of TPO-RAs increases platelet count, decreases bleeding symptoms and improves health-related quality of life. Moreover, TPO-RAs are well tolerated with minor side effects. CONCLUSION Although long term efficacy and safety of TPO-RAs still require further investigations, their use is gradually expanding in the clinical practice of children with ITP.
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Affiliation(s)
- Giuseppe Lassandro
- Department of Biomedical Science and Human Oncology-Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Valentina Palladino
- Department of Biomedical Science and Human Oncology-Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Giovanni C D Vecchio
- Department of Biomedical Science and Human Oncology-Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Viviana V Palmieri
- Department of Biomedical Science and Human Oncology-Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Paola C Corallo
- Department of Biomedical Science and Human Oncology-Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Maria F Faienza
- Department of Biomedical Science and Human Oncology-Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Paola Giordano
- Department of Biomedical Science and Human Oncology-Pediatric Unit, University of Bari "Aldo Moro", Bari, Italy
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Giordano P, Delvecchio M, Lassandro G, Valente F, Palladino V, Chiarito M, Wasniewska M, Faienza MF. Can Anti-Thyroid Antibodies Influence the Outcome of Primary Chronic Immune Thrombocytopenia in Children? Endocr Metab Immune Disord Drug Targets 2020; 20:351-355. [DOI: 10.2174/1871530319666190905161347] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 07/16/2019] [Accepted: 07/29/2019] [Indexed: 11/22/2022]
Abstract
Background:
Immune thrombocytopenia (ITP) is an acquired immune mediated disorder
characterized by isolated thrombocytopenia. Pediatric ITP patients can develop autoantibodies such as
anti-thyroglobulin (TG) and anti-thyroperoxidase (TPO), even in the absence of clinical signs of autoimmune
disease.
Objective:
The purpose of this article is to provide a review about: 1) the prevalence of positivity of
anti-thyroid antibodies (TPO and TG) in pediatric patients with chronic ITP; 2) the role of autoimmune
thyroiditis on the outcome of chronic ITP.
Method:
The authors individually completed a review of the literature for this article. Retrospective
and prospective clinical studies with pediatric cohorts were considered.
Results:
From the analysis of data, we found 4 papers which included studies only on pediatric population,
and which corresponded to selected criteria. Pediatric ITP patients have been shown to have a
statistically significant prevalence of anti-thyroid antibodies over healthy controls (11.6-36% versus
1.2-1.3%). No correlation has been found between the platelet count and the prevalence of positive
anti-thyroid antibodies at any time of the follow up.
Conclusion:
The results of our bibliographic research demonstrated that: a) pediatric patients with
chronic ITP tend to have a statistically significant prevalence of anti-thyroid antibodies positivity respect
to general pediatric population; b) there are no clear data about the role of autoimmune thyroiditis
as prognostic factor for chronic course of ITP in pediatric age.
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Affiliation(s)
- Paola Giordano
- Department of Biomedical Sciences and Human Oncology, University of Bari “A. Moro”, Bari, Italy
| | - Maurizio Delvecchio
- Department of metabolic diseases, clinic genetics and diabetology, “Giovanni XXIII” Children’s Hospital, Bari, Italy
| | - Giuseppe Lassandro
- Department of Biomedical Sciences and Human Oncology, University of Bari “A. Moro”, Bari, Italy
| | - Federica Valente
- Department of Biomedical Sciences and Human Oncology, University of Bari “A. Moro”, Bari, Italy
| | - Valentina Palladino
- Department of Biomedical Sciences and Human Oncology, University of Bari “A. Moro”, Bari, Italy
| | - Mariangela Chiarito
- Department of Biomedical Sciences and Human Oncology, University of Bari “A. Moro”, Bari, Italy
| | - Malgorzata Wasniewska
- Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy
| | - Maria F. Faienza
- Department of Biomedical Sciences and Human Oncology, University of Bari “A. Moro”, Bari, Italy
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10
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Giordano P, Lassandro G, Barone A, Cesaro S, Fotzi I, Giona F, Ladogana S, Miano M, Marzollo A, Nardi M, Notarangelo LD, Pession A, Ruggiero A, Russo G, Saracco P, Spinelli M, Tolva A, Tornesello A, Palladino V, Del Vecchio GC. Use of Eltrombopag in Children With Chronic Immune Thrombocytopenia (ITP): A Real Life Retrospective Multicenter Experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Front Med (Lausanne) 2020; 7:66. [PMID: 32181255 PMCID: PMC7059456 DOI: 10.3389/fmed.2020.00066] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 02/13/2020] [Indexed: 01/19/2023] Open
Abstract
Background: The thrombopoietin receptor agonist eltrombopag has been shown to be safe and effective for children with chronic immune thrombocytopenia (ITP). The aim of the present study was to characterize eltrombopag use in current clinical practice. Material and Methods: This is a retrospective multicenter study conducted in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). The primary objective of the study was to determine the prevalence of eltrombopag use in Italian children affected by chronic ITP, after EMA authorization for pediatric age. The secondary objective was to assess efficacy in the first 6 months and safety during the whole period of eltrombopag treatment in current clinical practice. A total of 386 children with chronic ITP were retrospectively enrolled and eligible for analysis. Among these patients, 71 received eltrombopag. Results: The prevalence of eltrombopag use was 19% (95% CI 0.15–0.23). Thirty-one patients (44%) were male and 40 patients (56%) were female. The median age at the first dose of eltrombopag was 12 years (3–17 years). The median duration of eltrombopag treatment was 11 months (1–32 months) and the median starting dose was 50 mg/day (12, 5–75 mg/day). Thirty-two patients (45%) required one or more concomitant ITP medications during the first 6 months of treatment with eltrombopag. Thirty-nine patients (55%) never required concomitant medications. Median platelet counts and proportion of patients achieving the target platelet count of at least 30 × 109/L and 100 × 109/L significantly increased during the first 6 months of treatment (p < 0.0001). Additionally, eltrombopag has been proved effective in the absence of concomitant therapies. The most common Adverse Events were headache (7%) and thrombocytosis (6%). Conclusion: Our study highlighted the crucial role of eltrombopag as second line treatment in children with chronic ITP.
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Affiliation(s)
- Paola Giordano
- Pediatric Unit, Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Giuseppe Lassandro
- Pediatric Unit, Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Angelica Barone
- Department of Pediatric Onco-Hematology, University Hospital of Parma, Parma, Italy
| | - Simone Cesaro
- Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Ilaria Fotzi
- Department Pediatric Hematology Oncology, Azienda Ospedaliero Universitaria A. Meyer Children Hospital, Florence, Italy
| | - Fiorina Giona
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Saverio Ladogana
- Department of Hematology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Maurizio Miano
- Clinical and Experimental Hematology Unit, "G. Gaslini" Children's Hospital, Genoa, Italy
| | - Antonio Marzollo
- Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, Azienda Ospedaliera-University of Padova, Padua, Italy
| | - Margherita Nardi
- Pediatric Hematology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | | | - Andrea Pession
- Department of Pediatrics, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Antonio Ruggiero
- Pediatric Oncology Unit, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanna Russo
- Pediatric Hemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Paola Saracco
- Pediatric Hematology, Department of Pediatrics, University Hospital Città della Salute e della Scienza, Turin, Italy
| | - Marco Spinelli
- Hemato-Oncology Unit, Fondazione MBBM, San Gerardo Hospital, Monza, Italy
| | - Alessandra Tolva
- Pediatric Hematology/Oncology, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Assunta Tornesello
- Pediatric Hematology Oncology, Presidio Ospedaliero Vito Fazzi, Lecce, Italy
| | - Valentina Palladino
- Pediatric Unit, Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Giovanni Carlo Del Vecchio
- Pediatric Unit, Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
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11
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Ottaviano G, Marinoni M, Graziani S, Sibson K, Barzaghi F, Bertolini P, Chini L, Corti P, Cancrini C, D'Alba I, Gabelli M, Gallo V, Giancotta C, Giordano P, Lassandro G, Martire B, Angarano R, Mastrodicasa E, Bava C, Miano M, Naviglio S, Verzegnassi F, Saracco P, Trizzino A, Biondi A, Pignata C, Moschese V. Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2019; 8:273-282. [PMID: 31377437 DOI: 10.1016/j.jaip.2019.07.032] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Revised: 07/14/2019] [Accepted: 07/16/2019] [Indexed: 01/19/2023]
Abstract
BACKGROUND Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients.
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Affiliation(s)
| | - Maddalena Marinoni
- Paediatric Department, ASST-Sette Laghi, "F. Del Ponte" Hospital, Varese, Italy
| | - Simona Graziani
- Paediatric Immunopathology and Allergology Unit, Tor Vergata University Hospital, University of Roma Tor Vergata, Rome, Italy
| | - Keith Sibson
- Department of Haematology, Great Ormond Street Hospital, London, United Kingdom
| | - Federica Barzaghi
- Paediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Patrizia Bertolini
- Paediatric Hematology Oncology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Loredana Chini
- Paediatric Immunopathology and Allergology Unit, Tor Vergata University Hospital, University of Roma Tor Vergata, Rome, Italy
| | - Paola Corti
- Paediatric Haematology, Fondazione MBBM, Monza, Italy
| | - Caterina Cancrini
- University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Irene D'Alba
- Paediatric Haematology-Oncology, Maternal Infant Hospital "G. Salesi", Ancona, Italy
| | - Maria Gabelli
- Department of Women's and Children's Health, Pediatric Onco-Hematology Unit, University of Padova, Padova, Italy
| | - Vera Gallo
- Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy
| | - Carmela Giancotta
- University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Rome, Italy
| | - Paola Giordano
- Department of Biomedical Sciences and Human Oncology, University "A. Moro", Bari, Italy
| | - Giuseppe Lassandro
- Department of Biomedical Sciences and Human Oncology, University "A. Moro", Bari, Italy
| | - Baldassare Martire
- Paediatric Hematology Oncology Unit, "Policlinico-Giovanni XXII" Hospital, University of Bari, Bari, Italy
| | - Rosa Angarano
- Paediatric Hematology Oncology Unit, "Policlinico-Giovanni XXII" Hospital, University of Bari, Bari, Italy
| | | | - Cecilia Bava
- Haematology Unit, IRCCS Istituto "G. Gaslini", Genova, Italy
| | - Maurizio Miano
- Haematology Unit, IRCCS Istituto "G. Gaslini", Genova, Italy
| | - Samuele Naviglio
- Pediatric Hematology-Oncology, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy
| | - Federico Verzegnassi
- Pediatric Hematology-Oncology, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy
| | - Paola Saracco
- Paediatric Haematology, Department of Paediatrics, University Hospital Città della Salute e della Scienza di Torino, Torino, Italy
| | - Antonino Trizzino
- Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina and Benfratelli Hospital, Palermo, Italy
| | - Andrea Biondi
- Paediatric Haematology, Milano-Bicocca University, Monza, Italy
| | - Claudio Pignata
- Department of Women's and Children's Health, Pediatric Onco-Hematology Unit, University of Padova, Padova, Italy
| | - Viviana Moschese
- Paediatric Immunopathology and Allergology Unit, Tor Vergata University Hospital, University of Roma Tor Vergata, Rome, Italy
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12
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Goel R, Chopra S, Tobian AAR, Ness PM, Frank SM, Cushing M, Vasovic L, Kaicker S, Takemoto C, Josephson CD, Nellis M, Bussel J, Krishnamurti L. Platelet transfusion practices in immune thrombocytopenia related hospitalizations. Transfusion 2018; 59:169-176. [PMID: 30520045 DOI: 10.1111/trf.15069] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 08/28/2018] [Accepted: 08/29/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND The role of platelet transfusions in management of Immune Thrombocytopenia (ITP) remains controversial. Current guidelines recommend that platelet transfusions in ITP be reserved for catastrophic hemorrhage or invasive surgical procedures. This study assesses the nationwide platelet transfusion practices in hospitalized children and adults with ITP. STUDY DESIGN AND METHODS We studied hospitalizations with ITP as the primary admitting diagnosis from 2010-2014 in National Inpatient Sample (NIS), the largest all-payer inpatient database. Univariate and multivariable logistic regression analyses were used to determine factors predicting platelet transfusions. Sampling weights were applied to generate nationally representative estimates. Propensity score matching was used to perform sensitivity analyses. RESULTS From 2010 to 2014, there were 78,376 admissions with ITP as the primary admission diagnosis (mean ± SD age: 45 ± 27 years; females 56%, children [age < 18 years] 22%) and 282,285 with ITP as one of all the admission diagnoses. Overall, 27% admissions with ITP as primary (children 4%) and 15% admissions with ITP as one of all the diagnoses documented at least one platelet transfusion. On multivariable adjustment the following factors were associated with worsening disease severity and a higher odds of platelet transfusion, adult age (adjOR = 9.03, 95% CI = 7.40-11.02), male gender (adjOR = 1.21, 95% CI = 1.11-1.31), bleeding occurrence (intracranial/gastrointestinal/genitourinary/epistaxis) (adjOR = 1.78, 95% CI = 1.61-1.96), admission to rural non-teaching hospital (adjOR = 1.85, 95% CI = 1.52-2.22), and small bed-size hospital (adjOR = 1.23, 95% CI = 1.05-1.45). Of admissions reporting platelet transfusions, only 26% reported a bleeding complication, and 11% had a major operating-room surgery/procedure. Overall, 65% of transfused patients had neither bleeding nor a major operative procedure during the hospitalization. Admissions with platelet transfusions had a significantly longer mean length of hospitalization 2.2 days (95% CI = 1.96-2.41, p < 0.001), and accrued higher mean total hospital charges; $31,150 USD (95% CI = 27,644-34,656, p < 0.001). However, platelet transfusions were not associated with in-hospital mortality (adjOR = 1.02, 95% CI = 0.73-1.45, p = 0.892). CONCLUSION Platelets are administered to a small fraction of the hospitalized ITP patients. In a majority of these cases however, platelet usage does not appear to be concordant with the current guidelines or associated with improvement in clinical outcomes.
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Affiliation(s)
- Ruchika Goel
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland.,Division of Hematology Oncology, Simmons Cancer Institute at SIU School of Medicine, Springfield, Illinois
| | - Saurav Chopra
- Department of Pathology, University of Iowa School of Medicine, Iowa City, Iowa
| | - Aaron A R Tobian
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland
| | - Paul M Ness
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland
| | - Steven M Frank
- Department of Anesthesiology/Critical Care Medicine and the Armstrong Institute for Patient Safety and Quality, Johns Hopkins University, Baltimore, Maryland
| | | | | | | | - Clifford Takemoto
- Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland
| | - Cassandra D Josephson
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.,Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Department of Pediatrics, Division of Hematology/Oncology, Emory University School of Medicine, Atlanta, Georgia
| | | | | | - Lakshmanan Krishnamurti
- Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Department of Pediatrics, Division of Hematology/Oncology, Emory University School of Medicine, Atlanta, Georgia
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13
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Grimaldi-Bensouda L, Nordon C, Leblanc T, Abenhaim L, Allali S, Armari-Alla C, Berger C, Courcoux MF, Fouyssac F, Guillaumat C, Guitton C, Le Moine P, Mazingue F, Pondarré C, Thomas C, Pasquet M, Perel Y, Leverger G, Aladjidi N. Childhood immune thrombocytopenia: A nationwide cohort study on condition management and outcomes. Pediatr Blood Cancer 2017; 64. [PMID: 27905681 DOI: 10.1002/pbc.26389] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 10/29/2016] [Accepted: 11/08/2016] [Indexed: 01/19/2023]
Abstract
OBJECTIVES Nationwide prospective cohort study exploring (i) the factors associated with treatment initiation (vs. watchful waiting) in children with primary immune thrombocytopenia (ITP) followed in routine clinical practice and (ii) the predictors of chronicity at 12 months. PROCEDURE Between 2008 and 2013, 23 centers throughout France consecutively included 257 children aged 6 months-18 years and diagnosed with primary ITP over a 5-year period. Data on ITP clinical features along with medical management were collected at baseline and 12 months. Multivariate logistic regressions were used to determine (i) and (ii) as defined above, providing odds ratio (OR) with 95% confidence interval (95% CI). RESULTS One hundred thirty-seven (53%) children were males, median age was 4.6 years, median platelet count was 7 × 109/l, and 214 (81%) patients initiated medication. Factors independently associated with treatment initiation included platelet counts <10 × 109/l (P < 0.0001) and mucocutaneous bleeding symptoms at baseline (P < 0.001). At 12 months, data were available for 211 (82%) children, of whom 160 (74%) had recovered. Predictors of chronicity included female gender (OR = 2.2; 95% CI = 1.0-4.8), age ≥10 years (OR = 2.6; 95% CI = 1.1-6.0), and platelet counts ≥10 × 109 /l (OR = 3.2; 95% CI = 1.5-6.9). CONCLUSIONS In routine clinical practice, the decision to apply a watchful waiting strategy seems to be driven by platelet counts even in the absence of bleeding symptoms, resulting in treatment being initiated in more than 80% of the children surveyed. Overall, younger children with ITP showed good prognosis, with lower platelet counts and, to a lesser extent, male gender predicting more favorable outcomes.
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Affiliation(s)
| | | | - Thierry Leblanc
- Department of Pediatric Hematology, Robert-Debré Hospital, AP-HP, Paris, France.,French Reference Center for Rare Diseases and Autoimmune Cytopenias of Childhood (CEREVANCE), Pellegrin Hospital, Bordeaux, France
| | | | - Slimane Allali
- Department of General Pediatrics, Necker Hospital, AP-HP and Paris Descartes University, Paris, France
| | - Corinne Armari-Alla
- Department of Pediatric Hematology, Grenoble University Hospital, Grenoble, France
| | - Claire Berger
- Department of Pediatric Hematology, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Mary-France Courcoux
- Department of Immunology and Hematology, Armand-Trousseau Hospital, Paris, France
| | - Fanny Fouyssac
- Department of Pediatric Hematology, Nancy University Hospital, Vandoeuvre-les-Nancy, France
| | - Cécile Guillaumat
- Department of General Pediatrics, Sud-Francilien Hospital, Corbeil-Essonnes, France
| | - Corinne Guitton
- Department of Pediatric Rheumatology and Hematology, Bicêtre Hospital, Le Kremlin-Bicêtre, France
| | - Philippe Le Moine
- Department of Pediatrics and Clinical Genetics, Morvan University Hospital, Brest, France
| | - Françoise Mazingue
- Department of Pediatric Hematology, Lille University Hospital, Lille, France
| | - Corinne Pondarré
- Department of Pediatrics, Intercommunal Hospital, Creteil, France
| | - Caroline Thomas
- Pediatric Intensive Care and Onco-Hematology Units, Nantes University Hospital, Nantes, France
| | - Marlène Pasquet
- Department of Pediatric Hematology and Immunology, Purpan University Hospital and INSERM U1037, Toulouse, France
| | - Yves Perel
- French Reference Center for Rare Diseases and Autoimmune Cytopenias of Childhood (CEREVANCE), Pellegrin Hospital, Bordeaux, France.,Department of Pediatric Hematology, CIC 1401, INSERM CICP, Pellegrin Hospital, Bordeaux, France
| | - Guy Leverger
- French Reference Center for Rare Diseases and Autoimmune Cytopenias of Childhood (CEREVANCE), Pellegrin Hospital, Bordeaux, France.,Department of Immunology and Hematology, Armand-Trousseau Hospital, Paris, France
| | - Nathalie Aladjidi
- French Reference Center for Rare Diseases and Autoimmune Cytopenias of Childhood (CEREVANCE), Pellegrin Hospital, Bordeaux, France.,Department of Pediatric Hematology, CIC 1401, INSERM CICP, Pellegrin Hospital, Bordeaux, France
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14
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Ladogana S, Maruzzi M, Samperi P, Perrotta S, Del Vecchio GC, Notarangelo LD, Farruggia P, Verzegnassi F, Masera N, Saracco P, Fasoli S, Miano M, Girelli G, Barcellini W, Zanella A, Russo G. Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2017; 15:259-267. [PMID: 28151390 PMCID: PMC5448833 DOI: 10.2450/2016.0072-16] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Accepted: 11/09/2016] [Indexed: 01/20/2023]
Abstract
Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia.The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants.
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Affiliation(s)
- Saverio Ladogana
- Paediatric Onco-haematology Unit, “Casa Sollievo della Sofferenza” Hospital, IRCCS, San Giovanni Rotondo, Italy
| | - Matteo Maruzzi
- Paediatric Onco-haematology Unit, “Casa Sollievo della Sofferenza” Hospital, IRCCS, San Giovanni Rotondo, Italy
| | - Piera Samperi
- Paediatric Onco-haematology Unit, Azienda Policlinico “Vittorio Emanuele”, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Silverio Perrotta
- Department of Women, Children and General and Specialized Surgery, Second University of Naples, Naples, Italy
| | | | - Lucia D. Notarangelo
- Paediatric Onco-haematology Unit, Children’s Hospital, Spedali Civili, Brescia, Italy
| | - Piero Farruggia
- Paediatric Onco-haematology Unit, Civico Hospital, Palermo, Italy
| | | | - Nicoletta Masera
- Paediatric Department, University of Milano-Bicocca, “San Gerardo” Hospital, Monza, Italy
| | - Paola Saracco
- Paediatric and Adolescent Science Department, University of Turin, Turin, Italy
| | - Silvia Fasoli
- Paediatric Unit, “Carlo Poma” Hospital, Mantua, Italy
| | - Maurizio Miano
- Clinical and Experimental Haematology Unit, “G. Gaslini” Children’s Hospital, Genoa, Italy
| | - Gabriella Girelli
- Immunohaematology and Transfusion Medicine Unit, Policlinico Umberto I, Sapienza University, Rome, Italy
| | - Wilma Barcellini
- Onco-haematology, Physiopathology of Anaemia Unit, IRCCS Ca’ Granda Foundation, Ospedale Maggiore Policlinico, Milan, Italy
| | - Alberto Zanella
- Onco-haematology, Physiopathology of Anaemia Unit, IRCCS Ca’ Granda Foundation, Ospedale Maggiore Policlinico, Milan, Italy
| | - Giovanna Russo
- Paediatric Onco-haematology Unit, Azienda Policlinico “Vittorio Emanuele”, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
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15
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Miano M, Ramenghi U, Russo G, Rubert L, Barone A, Tucci F, Farruggia P, Petrone A, Mondino A, Lo Valvo L, Crescenzio N, Bellia F, Olivieri I, Palmisani E, Caviglia I, Dufour C, Fioredda F. Mycophenolate mofetil for the treatment of children with immune thrombocytopenia and Evans syndrome. A retrospective data review from the Italian association of paediatric haematology/oncology. Br J Haematol 2016; 175:490-495. [PMID: 27447678 DOI: 10.1111/bjh.14261] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 06/07/2016] [Indexed: 12/15/2022]
Abstract
Mycophenolate mofetil (MMF) has been shown to be effective in children with immune thrombocytopenia (ITP) and Evans syndrome (ES), but data from larger series and details on the timing of the response are lacking. We evaluated 56 children treated with MMF for ITP (n = 40) or ES (n = 16), which was primary or secondary to autoimmune lymphoproliferative syndrome -related syndrome (ARS). Thirty-five of the 54 evaluable patients (65%) achieved a partial (18%) or complete (46%) response after a median (range) of 20 (7-137) and 37 (7-192) d, respectively. ITP and ES patients responded in 58% and 81% of cases (P = not significant, ns), with complete response in 32% and 81% (P = 0·01), respectively. 60% and 73% of children with primary disease and ARS responded (P = ns) with complete response in 34% and 68% of cases (P = 0·01), respectively. Six of 35 (17%) children relapsed after a median of 283 d (range 189-1036). Limited toxicity was observed in four patients. The median durations of treatment and follow-up were seven and 12·7 months, respectively. This is the largest reported cohort of patients treated with MMF for ITP/ES. The results show that MMF is effective and safe and provides a relatively quick response, suggesting that it has a potential role as an alternative to more aggressive and expensive second/further-line treatments.
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Affiliation(s)
- Maurizio Miano
- Haematology Unit, I.R.C.C.S. Istituto Giannina Gaslini, Genoa, Italy.
| | - Ugo Ramenghi
- Haematology Unit, Paediatric Department, University of Turin, Turin, Italy
| | - Giovanna Russo
- Department of Paediatrics, Unit of Paediatric Haematology and Oncology, University of Catania, Catania, Italy
| | - Laura Rubert
- Haematology-Oncology Unit, I.R.C.C.S. Policlinico Fondazione San Matteo Pavia, Pavia, Italy
| | - Angelica Barone
- Paediatric and Onco-Haematology Unit, University Hospital of Parma, Parma, Italy
| | - Fabio Tucci
- Paediatric Haematology-Oncology Unit, Ospedale Pediatrico Meyer, Florence, Italy
| | - Piero Farruggia
- Paediatric Haematology and Oncology Unit, "G. Di Cristina" Children's Hospital, Palermo, Italy
| | | | - Anna Mondino
- Haematology Unit, Paediatric Department, University of Turin, Turin, Italy
| | - Laura Lo Valvo
- Department of Paediatrics, Unit of Paediatric Haematology and Oncology, University of Catania, Catania, Italy
| | | | - Francesco Bellia
- Department of Paediatrics, Unit of Paediatric Haematology and Oncology, University of Catania, Catania, Italy
| | - Irene Olivieri
- Haematology Unit, I.R.C.C.S. Istituto Giannina Gaslini, Genoa, Italy
| | - Elena Palmisani
- Haematology Unit, I.R.C.C.S. Istituto Giannina Gaslini, Genoa, Italy
| | - Ilaria Caviglia
- Infectious Diseases Unit, I.R.C.C.S. Istituto Giannina Gaslini, Genoa, Italy
| | - Carlo Dufour
- Haematology Unit, I.R.C.C.S. Istituto Giannina Gaslini, Genoa, Italy
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16
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Giordano P, Cascioli S, Lassandro G, Marcellini V, Cardinale F, Valente F, Locatelli F, Carsetti R. B-cell hyperfunction in children with immune thrombocytopenic purpura persists after splenectomy. Pediatr Res 2016; 79:262-70. [PMID: 26492283 DOI: 10.1038/pr.2015.211] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 08/04/2015] [Indexed: 01/19/2023]
Abstract
BACKGROUND Immune thrombocytopenic purpura (ITP) is characterized by reduced platelet count secondary to immune-mediated destruction, this results in an increased bleeding risk. Autoantibodies binding to platelets tag them for premature destruction in the spleen. For this reason, splenectomy is often performed as treatment of chronic forms of disease that are resistant to pharmacological therapy. METHODS We studied 30 patients with ITP and compared them with age-matched controls. RESULTS We show that B cells of patients with chronic ITP are intrinsically hyperreactive, producing more than normal IgG in vivo and plasma cells in vitro. In normal individuals after splenectomy, a significant depletion of memory B cells is observed, associated with loss of reactivity to CpG oligodeoxynucleotide and consequent inability to form antibody-producing cells. In Enzyme-Linked ImmunoSpot Methods, we compared three splenectomized ITP patients relapsing after surgery, 30 healthy controls, and 37 individuals splenectomized for trauma, spherocytosis, thalassemia, nonhematological tumor, and other diseases. CONCLUSIONS We confirmed that B cells of ITP patients remain hyperreactive in vitro and form high numbers of antibody-producing cells after splenectomy. Thus, chronic ITP may be associated with intrinsic B-cell hyperfunction, leading to the production of antibodies with multiple specificities including that against platelets.
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Affiliation(s)
- Paola Giordano
- Division of Hematology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", University of Bari "Aldo Moro", Bari, Italy
| | - Simona Cascioli
- Immunology and Pharmacotherapy Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Giuseppe Lassandro
- Division of Hematology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", University of Bari "Aldo Moro", Bari, Italy
| | - Valentina Marcellini
- Immunology and Pharmacotherapy Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Fabio Cardinale
- Division of Pulmonology, Allergy, and Immunology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", Bari, Italy
| | - Federica Valente
- Division of Hematology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", University of Bari "Aldo Moro", Bari, Italy
| | - Franco Locatelli
- Department of Oncohaematology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.,Department of Pediatric Science, University of Pavia, Pavia, Italy
| | - Rita Carsetti
- Immunology and Pharmacotherapy Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.,Department of Laboratories and Diagnostic Immunology Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
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17
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Abstract
Chronic thrombocytopenias are pathological conditions defined as a persistent platelet count below the normal range for more than 6-12 months, clinically characterized by mucocutaneous bleeding. Recently, an International Working Group of expert clinicians has redefined standard terminology and definitions of primary and secondary chronic immune thrombocytopenia (ITP). A document issued on acute childhood idiopathic thrombocytopenic purpura (AIEOP) provides parents and physicians with guidelines for the management of chronic ITP and gives prominence to the periodic re-evaluation of differential diagnosis. The majority of chronic ITP children do not require pharmacological treatments, especially if symptoms are absent or minimal and the treatment decision depends on several factors, in particular clinical conditions rather than platelets count. The recommendations distinguish three therapeutic strategies: emergency or symptomatic treatment, maintenance therapy and treatment aiming at definitive remission. Experimental/off-label treatment of chronic ITP are reported in the literature, such as the use of rituximab. Currently, other drugs (thrombopoiesis stimulating factors, mycophenolate, dapsone, danazol, azathioprine, rFVIIa, cyclophosphamide, vinca alkaloids and cyclosporine) are recommended in special cases or trials.
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Guimarães LE, Baker B, Perricone C, Shoenfeld Y. Vaccines, adjuvants and autoimmunity. Pharmacol Res 2015; 100:190-209. [PMID: 26275795 PMCID: PMC7129276 DOI: 10.1016/j.phrs.2015.08.003] [Citation(s) in RCA: 154] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 08/05/2015] [Indexed: 12/15/2022]
Abstract
Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future.
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Affiliation(s)
- Luísa Eça Guimarães
- The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Britain Baker
- The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Carlo Perricone
- Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Italy
| | - Yehuda Shoenfeld
- The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Incumbent of the Laura Schwarz-kipp chair for research of autoimmune diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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Perricone C, Ceccarelli F, Nesher G, Borella E, Odeh Q, Conti F, Shoenfeld Y, Valesini G. Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases. Immunol Res 2015; 60:226-35. [PMID: 25427992 DOI: 10.1007/s12026-014-8597-x] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per μl. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-γ and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this.
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Affiliation(s)
- Carlo Perricone
- Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy
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20
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Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality. Blood 2015; 125:1470-6. [PMID: 25588677 DOI: 10.1182/blood-2014-10-605493] [Citation(s) in RCA: 141] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
While platelets are primary mediators of hemostasis, there is emerging evidence to show that they may also mediate pathologic thrombogenesis. Little data are available on risks and benefits associated with platelet transfusions in thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP). This study utilized the Nationwide Inpatient Sample to evaluate the current in-hospital platelet transfusion practices and their association with arterial/venous thrombosis, acute myocardial infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age and gender-adjusted odds ratios (adjOR) associated with platelet transfusions were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and 79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and 25.8% ITP admissions. Platelet transfusions in TTP were associated with higher odds of arterial thrombosis (adjOR = 5.8, 95%CI = 1.3-26.6), AMI (adjOR = 2.0, 95%CI = 1.2-3.3) and mortality (adjOR = 2.0,95%CI = 1.3-3.0), but not venous thrombosis. Platelet transfusions in HIT were associated with higher odds of arterial thrombosis (adjOR = 3.4, 95%CI = 1.2-9.5) and mortality (adjOR = 5.2, 95%CI = 2.6-10.5) but not venous thrombosis. Except for AMI, all relationships remained significant after adjusting for clinical severity and acuity. No associations were significant for ITP. Platelet transfusions are associated with higher odds of arterial thrombosis and mortality among TTP and HIT patients.
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21
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Rinaldi M, Perricone C, Ortega-Hernandez OD, Perricone R, Shoenfeld Y. Immune thrombocytopaenic purpura: an autoimmune cross-link between infections and vaccines. Lupus 2014; 23:554-67. [PMID: 24763539 DOI: 10.1177/0961203313499959] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Immune thrombocytopaenic purpura (ITP) is an autoimmune systemic disease detectable by the presence of low blood platelets count (<10(5)/µl) and the production of autoantibodies against glycoproteins expressed on the platelet surface. The clinical course is often acute, and life-threatening events may occur especially in children, with 52% of paediatric patients recovering either spontaneously or after treatment. A chronic ITP evolution is observed in 64% of adults, of whom 12% will develop an overlapping autoimmune disease. Several microbial agents such as CagA-positive Helicobacter pylori or Candida albicans and a number of viruses including CMV, EBV or HIV can potentially trigger ITP through molecular mimicry. Moreover, ITP improves after treatment of the underlying infection. Similarly, vaccines such as MMR may prompt ITP (IRR 5.48, 1.61-18.64, p < 0.006). Early recognition of the underlying microbial trigger and the removal of modifiable aetiopathogenetic factors should be integrated as a complementary treatment strategy in all patients who do not readily improve with standard ITP care.
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Affiliation(s)
- M Rinaldi
- 1Rheumatology, Allergology and Clinical Immunology, Department of Internal Medicine, University of Rome Tor Vergata, Italy
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22
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Comparación de guías internacionales sobre púrpura trombocitopénica autoinmunitaria primaria. Med Clin (Barc) 2014; 143:408-19. [DOI: 10.1016/j.medcli.2014.02.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Accepted: 02/06/2014] [Indexed: 11/23/2022]
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23
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Clinical use of polyvalent immunoglobulins. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2014; 11 Suppl 4:s33-9. [PMID: 24333311 DOI: 10.2450/2013.007s] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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24
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Grace RF. Standardized clinical assessment and management plans (SCAMPs): perspectives on a new method to understand treatment decisions and outcomes in immune thrombocytopenia. Semin Hematol 2014; 50 Suppl 1:S31-8. [PMID: 23664514 DOI: 10.1053/j.seminhematol.2013.03.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Modern evidence based guidelines in immune thrombocytopenia (ITP) are mostly based on expert opinion. Standardized clinical assessment and management plans (SCAMPs) are flexible, feedback-based practice guidelines that could be valuable for both managing patients with ITP and understanding treatment decisions and outcomes. At Boston Children's Hospital, we have implemented a SCAMP for patients with newly diagnosed and persistent ITP. To develop the algorithm, a group of local ITP experts devised an initial guideline, which was then modified by the attending hematologists who care for ITP patients until consensus was reached. Since deviations from the algorithm are encouraged, all clinicians did not need to agree with all aspects of the algorithm. At each clinic visit, clinicians fill out data collection forms explaining practice deviations. The goals of this process are to decrease practice variation and resource utilization and learn from the outcomes and deviations that occur to continually improve our practice. SCAMPs are an innovative approach to improve quality of care in ITP.
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Affiliation(s)
- Rachael F Grace
- Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
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25
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Loggetto SR, Braga JAP, Veríssimo MPDA, Bernardo WM, Medeiros L, Hoepers ATDC. Guidelines on the treatment of primary immune thrombocytopenia in children and adolescents: Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Guidelines Project: Associação Médica Brasileira - 2012. Rev Bras Hematol Hemoter 2014; 35:417-27. [PMID: 24478609 PMCID: PMC3905825 DOI: 10.5581/1516-8484.20130124] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 10/16/2013] [Indexed: 01/19/2023] Open
Affiliation(s)
| | | | | | - Wanderley Marques Bernardo
- Faculdade de Medicina da Universidade de São Paulo - USP, São Paulo, Brazil ; Associação Médica Brasileira - AMB, São Paulo, Brazil
| | | | - Andrea Thives de Carvalho Hoepers
- Centro de Hematologia e Hemoterapia de Santa Catarina - HEMOSC, Florianópolis, SC, Brazil ; Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil
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26
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Kuwana M. Helicobacter pylori-associated immune thrombocytopenia: Clinical features and pathogenic mechanisms. World J Gastroenterol 2014; 20:714-723. [PMID: 24574745 PMCID: PMC3921481 DOI: 10.3748/wjg.v20.i3.714] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Revised: 11/14/2013] [Accepted: 12/04/2013] [Indexed: 02/06/2023] Open
Abstract
Immune thrombocytopenia (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. There is growing evidence that the eradication of Helicobacter pylori (H. pylori) effectively increases platelet count in a considerable proportion of ITP patients infected with this bacterium. In the majority of ITP patients responding to H. pylori eradication therapy, the anti-platelet autoantibody response is completely resolved with no relapse for more than 7 years, indicating that the disease is cured. Therefore, adult patients with suspected ITP should be examined for H. pylori infection, and eradication therapy is recommended if the infection is present. Notably, however, the efficacy of H. pylori eradication therapy in ITP patients varies widely among countries, with a higher response rate in Japan compared with the United States and European countries other than Italy. The pathogenesis of H. pylori-associated ITP is still uncertain, although the mechanisms are known to involve multiple factors. H. pylori may modulate the Fcγ-receptor balance of monocytes/macrophages in favor of activating Fcγ receptors, and H. pylori components may mimic the molecular makeup of platelet antigens. Further studies of the pathogenic process of H. pylori-associated ITP may be useful for the development of new therapeutic strategies for ITP.
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27
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Alternative therapy for persistent childhood immune thrombocytopenic purpura unresponsive to intravenous immunoglobulin. Complement Ther Med 2013; 21:525-8. [DOI: 10.1016/j.ctim.2013.08.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2013] [Revised: 07/31/2013] [Accepted: 08/11/2013] [Indexed: 11/22/2022] Open
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28
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Yacob M, Raju RS, Vyas FL, Joseph P, Sitaram V. Management of colorectal cancer liver metastasis in a patient with immune thrombocytopaenia. Ann R Coll Surg Engl 2013; 95:e50-1. [PMID: 23484984 PMCID: PMC4098605 DOI: 10.1308/003588413x13511609957498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Immune thrombocytopaenia (ITP) was referred to previously as idiopathic thrombocytopaenic purpura and is usually of autoimmune or viral aetiology. Colorectal cancer liver metastasis with concomitant ITP is rare and only three cases have been reported in the English literature. Adverse effects of adjuvant chemotherapy may aggravate ITP. The sequencing of chemotherapy, operation for the primary and liver metastasis, and a decision on splenectomy is important. We present our experience in the management of a 52-year-old man who, having undergone anterior resection one year earlier for carcinoma of the rectum, presented with liver metastasis and ITP. He underwent splenectomy with hepatectomy prior to chemotherapy.
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Affiliation(s)
- M Yacob
- Department of HPB Surgery, Christian Medical College, Vellore, India.
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29
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Braga JAP, Loggetto SR, Hoepers ATDC, Bernardo WM, Medeiros L, Veríssimo MPDA. Guidelines on the diagnosis of primary immune thrombocytopenia in children and adolescents: Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Guidelines Project: Associação Médica Brasileira - 2012. Rev Bras Hematol Hemoter 2013; 35:358-65. [PMID: 24255621 PMCID: PMC3832318 DOI: 10.5581/1516-8484.20130105] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 07/20/2013] [Indexed: 01/19/2023] Open
Affiliation(s)
| | | | - Andrea Thives de Carvalho Hoepers
- Centro de Hematologia e Hemoterapia de Santa Catarina - HEMOSC,
Florianópolis, SC, Brazil
- Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC,
Brazil
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30
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Abstract
Primary immune thrombocytopenia (ITP) is one of the most common bleeding disorders of childhood. In most cases, it presents with sudden widespread bruising and petechiae in an otherwise well child. Thought to be mainly a disorder of antibody-mediated platelet destruction, ITP can be self-limited or develop into a chronic condition. In this review, we discuss current concepts of the pathophysiology and treatment approaches to pediatric ITP.
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31
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Anoop P. Immune thrombocytopenic purpura: historical perspective, current status, recent advances and future directions. Indian Pediatr 2012; 49:811-8. [PMID: 23144100 DOI: 10.1007/s13312-012-0195-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Immune thrombocytopenic purpura (ITP) has witnessed many changes and updates over the past decade. The definitions of disease subtypes, course and response to treatment have all been standardized recently. Consequent to the lack of an international consensus management guideline, wide variations exist in treatment practice. This is now being addressed to an extent by the much awaited ITP International Working Group 2010 recommendations. The pathophysiologic mechanisms have been unfolded at cellular, molecular and humoral levels. As a result, many recent advances have taken place in the management of this disorder. This review revisits the history of evolution of ITP, summarizes the current recommendations for management and lists the recent advances and future prospects in this field.
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Affiliation(s)
- P Anoop
- Department of Pediatric Hemato-Oncology, Great Ormond Street Hospital for Children, London, United Kingdom.
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32
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Kühne T, Imbach P. Management of children and adolescents with primary immune thrombocytopenia: controversies and solutions. Vox Sang 2012; 104:55-66. [PMID: 22804721 DOI: 10.1111/j.1423-0410.2012.01636.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The management including diagnostic procedures, prophylaxis, treatment and follow-up of patients with primary immune thrombocytopenia (ITP) in childhood is controversial due to limited clinical data, difficulties in the estimation of individual bleeding risk and heterogeneity of pathophysiology potentially causing various treatment responses. Advances in the management of children include increased international collaborations, improved quality of diagnosis and treatment, increased clinical data, refinement of consensus statements where clinical evidence is absent, new drugs and last but not least establishment of watch-and-wait strategies. The Intercontinental Cooperative ITP Study Group promotes international collaboration since more than 10 years based on a worldwide network and experience in registries. Future considerations include concentration of available resources, strengthening international collaboration, focusing on most important scientific and clinical questions, such as identification of the subgroup of patients that benefits most from prophylactic platelet-enhancing treatments and investigation of treatment endpoints other than concepts solely based on the platelet count, including bleeding symptoms, health-related quality of life and economical aspects of treatments.
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Affiliation(s)
- T Kühne
- Division of Oncology/Hematology, University Children's Hospital, Basel, Switzerland.
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Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura. Gene 2012; 505:53-6. [PMID: 22677268 DOI: 10.1016/j.gene.2012.05.050] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2012] [Revised: 05/08/2012] [Accepted: 05/23/2012] [Indexed: 11/22/2022]
Abstract
Derangement of genetic and immunological factors seems to have a pivotal role in the pathophysiology of immune thrombocytopenic purpura (ITP). We investigated interleukin(IL)-10 genetically determined expression in children with an acute progression of ITP (n=41) compared to young patients with chronic ITP (n=44) and healthy controls (n=60), and attempted to correlate IL-10 production with the course of the disease. We genotyped our study population for three single nucleotide polymorphisms at positions -1082 (A/G), -819 (C/T) and -592 (C/A) in the promoter region of the IL-10 gene. IL-10 levels were measured by enzyme-linked immunoassay. The IL-10 production in our study population was significantly higher in patients carrying the GCC haplotype than those bearing ACC and ATA haplotypes (6.9 ± 1.5 vs 3.6 ± 0.8 vs 3.3 ± 0.3, p=0.03). The serum concentration of IL-10 was significantly higher in patients with an acute course of their disease, who mainly carried the GCC haplotype (92%), compared to chronic subjects, bearing the non-GCC haplotypes, and controls [17 pg/mL (1.7-18) vs 3.5 pg/mL (0.6-11) vs 3 pg/mL (1-7), p<0.01)]. Our findings show that patients carrying the GCC-high producer IL-10 haplotype have an acute development of ITP and that IL-10 levels might represent a useful predictive biomarker of the disease course.
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Garnock-Jones KP. Eltrombopag: a review of its use in treatment-refractory chronic primary immune thrombocytopenia. Drugs 2011; 71:1333-53. [PMID: 21770480 DOI: 10.2165/11207390-000000000-00000] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Eltrombopag (Revolade(®)) is an orally bioavailable, low molecular weight, synthetic nonpeptide thrombopoietin receptor agonist, which selectively binds to the transmembrane and juxtamembrane domains of the thrombopoietin receptor on the surface of platelets, megakaryocytes and megakaryocyte precursor cells, resulting in responses similar to those induced by recombinant human thrombopoietin. Eltrombopag does not compete with thrombopoietin for its binding domain on the thrombopoietin receptor, and is highly selective. This article provides an overview of the pharmacological properties of eltrombopag and reviews the clinical efficacy and tolerability of the drug in adult patients with chronic primary immune thrombocytopenia (ITP). In well designed, 6-week and 6-month trials, eltrombopag was more effective than placebo at increasing platelet count and decreasing the incidence of bleeding in patients with treatment-refractory chronic ITP, and was generally well tolerated in these patients. Long-term (median duration 100 weeks) data from a noncomparative trial support these results. Importantly, previous splenectomy did not appear to have an effect on the efficacy of eltrombopag. As the first licensed oral thrombopoietin receptor agonist, eltrombopag may be a more convenient option than other ITP medications; however, it may be a costly option long term, as platelet counts generally return to baseline levels following treatment cessation, implying that continued treatment may be advised. Long-term treatment is often necessary in patients with chronic ITP, as curative rates with any treatment are very low. Eltrombopag was generally well tolerated in clinical trials in patients with chronic ITP. Hepatobiliary abnormalities occurred in a greater proportion of eltrombopag than placebo recipients; however, these were usually mild and reversible. Other potential concerns, such as thromboembolic events, cataracts and increased bone marrow reticulin, need to be further investigated. Eltrombopag is an effective treatment option for adult patients with chronic ITP and an increased risk of bleeding who are refractory to previous treatments, including splenectomy, as demonstrated in well designed clinical trials.
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35
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Rossi F, Mancusi S, Bellini G, Roberti D, Punzo F, Vetrella S, Matarese SMR, Nobili B, Maione S, Perrotta S. CNR2 functional variant (Q63R) influences childhood immune thrombocytopenic purpura. Haematologica 2011; 96:1883-5. [PMID: 21828121 DOI: 10.3324/haematol.2011.045732] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Immune thrombocytopenic purpura is an acquired autoimmune disorder that is the most common cause of thrombocytopenia in children. The endocannabinoid system is involved in immune regulation. We evaluated a common missense variant (CAA/CGG; Q63R) of the gene encoding the cannabinoid receptor type 2 (GeneID 1269) in 190 children with immune thrombocytopenic purpura and 600 healthy controls. The allelic frequencies and genotype distribution of the polymorphism in the patients were significant compared to control samples (P=0.006 and P=0.0001, respectively). Interestingly, when acute and chronic immune thrombocytopenic purpura patients were analyzed separately with respect to controls, a significant overrepresentation of the RR genotype and of the R allele was observed only for the chronic form (P=0.00021 and P=0.011, respectively). The relative odds ratio suggested the risk of developing chronic form was more than double in immune thrombocytopenic purpura children homozygous for the variant (odds ratio=2.349, 95% CI: 1.544-3.573; P<0.001).
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Affiliation(s)
- Francesca Rossi
- Department of Paediatrics, Second University of Naples, Naples, Italy
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36
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Bredlau AL, Semple JW, Segel GB. Management of immune thrombocytopenic purpura in children: potential role of novel agents. Paediatr Drugs 2011; 13:213-23. [PMID: 21692546 DOI: 10.2165/11591640-000000000-00000] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10 000/μL and the patient is asymptomatic, a 'watch and wait' strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of bleeding or a platelet count <10 000/μL, then treatment with glucocorticoids, intravenous immunoglobulin (IVIg), or anti-D are possible initial choices. Glucocorticoid treatment is the least expensive and is our usual first choice of therapy. Its use assumes that the blood counts and blood film have been evaluated to ensure the absence of evidence of alternative diagnoses, such as thrombotic thrombocytopenic purpura or incipient acute leukemia. IVIg is expensive and often causes severe headache, nausea and vomiting, and requires hospitalization at our institution. Anti-D therapy is also expensive and can only be used in patients who are Rhesus D positive. These therapies, even if only transiently effective, can be repeated if necessary. Children usually recover from newly diagnosed ITP, with or without multiple courses of medical therapy. If the disease becomes 'persistent' with severe thrombocytopenia and/or bleeding, and is no longer responsive to the three first-line therapies, the next approach includes the use of thrombopoietin receptor agonists or rituximab. When the disease persists for more than 1 year, it is considered chronic, and, if symptomatic, it may become necessary to consider third-line therapies, including splenectomy, alternative immunosuppressive agents, or combination or investigative chemoimmunotherapy. This review considers the indications, mechanism of action, and effectiveness of the traditional and novel treatment options for patients with ITP.
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Affiliation(s)
- Amy Lee Bredlau
- Department of Pediatrics, Division of Hematology/Oncology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
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Xu W, Wang TY, Becker RC. Enfermedades hematológicas: desde dentro del corazón. Rev Esp Cardiol 2011; 64:606-13. [DOI: 10.1016/j.recesp.2011.02.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Accepted: 02/22/2011] [Indexed: 10/18/2022]
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Russo G, Miraglia V, Branciforte F, Matarese SMR, Zecca M, Bisogno G, Parodi E, Amendola G, Giordano P, Jankovic M, Corti A, Nardi M, Farruggia P, Battisti L, Baronci C, Palazzi G, Tucci F, Ceppi S, Nobili B, Ramenghi U, De Mattia D, Notarangelo L. Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: a prospective, controlled, multicenter study. Pediatr Blood Cancer 2011; 56:273-8. [PMID: 20830773 DOI: 10.1002/pbc.22770] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia (ITP) in approximately half of eradicated patients. Data on children are limited to small case series. PROCEDURE Children from 16 centers in Italy, who were less than 18 years of age and diagnosed with chronic ITP (cITP), were screened for H. pylori infection. Positive patients underwent standard triple therapy with amoxicillin, clarithromycin, and omeprazole. The eradication response was defined as follows: complete response, platelet (PLT) count ≥ 150 × 10(9) /L; partial response, PLT count of at least 50 × 10(9) /L; no response, PLT count <50 × 10(9) /L. RESULTS Of 244 screened patients, 50 (20%) had H. pylori infection, 37 of which received eradication therapy and completed follow-up. Eradication was successful in 33/37 patients (89%). PLT recovery was demonstrated in 13/33 patients after eradication (39%), whereas spontaneous remission was observed in 17/166 (10%) H. pylori-negative patients (P < 0.005). Responders more often required second line eradication (9/13), whereas a second cycle was required in 3/20 non-responders (P < 0.005). CONCLUSIONS Among the large cohort of patients, those who underwent successful H. pylori eradication showed a significantly higher PLT response. Therefore, it may be appropriate to look for H. pylori and eventually eradicate it in children with cITP.
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Affiliation(s)
- Giovanna Russo
- Centro di Riferimento di Ematologia ed Oncologia Pediatrica, Università di Catania, Catania, Italy.
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Bolton-Maggs PHB, Kok VSL. Chronic immune thrombocytopenic purpura-who needs medication? Ann Hematol 2010; 89 Suppl 1:61-5. [PMID: 20309689 DOI: 10.1007/s00277-010-0918-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2009] [Accepted: 02/01/2010] [Indexed: 01/20/2023]
Abstract
Chronic ITP (immune thrombocytopenic purpura; now defined as duration of more than 12 months) is not always associated with significant bleeding problems so that most children and adults can be managed expectantly with no medication unless surgery, accidents or other pathology mandate it. A cut-off platelet count of 30 x 10(9)/l divides a group with no increased mortality from those whose risk is greater and in whom medication is usually appropriate. There is increasing recognition of long-term morbidity and mortality associated with immune suppression induced by medication and more recently new concerns have arisen about the long-term vascular complications of splenectomy. A more conservative approach to medication is warranted in many patients with chronic ITP.
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Affiliation(s)
- Paula H B Bolton-Maggs
- Department of Clinical Haematology, Central Manchester and Manchester Children's University NHS Foundation Trust, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK,
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