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Triggianese P, Vitale A, Lopalco G, Mayrink Giardini HA, Ciccia F, Al-Maghlouth I, Ruscitti P, Sfikakis PP, Iannone F, de Brito Antonelli IP, Patrone M, Asfina KN, Di Cola I, Laskari K, Gaggiano C, Tufan A, Sfriso P, Dagna L, Giacomelli R, Hinojosa-Azaola A, Ragab G, Fotis L, Direskeneli H, Spedicato V, Dagostin MA, Iacono D, Ali HH, Cipriani P, Sota J, Kardas RC, Bindoli S, Campochiaro C, Navarini L, Gentileschi S, Martín-Nares E, Torres-Ruiz J, Saad MA, Kourtesi K, Alibaz-Oner F, Sevik G, Iagnocco A, Makowska J, Govoni M, Monti S, Maggio MC, La Torre F, Del Giudice E, Hernández-Rodríguez J, Bartoloni E, Emmi G, Chimenti MS, Maier A, Simonini G, Conti G, Olivieri AN, Tarsia M, De Paulis A, Lo Gullo A, Więsik-Szewczyk E, Viapiana O, Ogunjimi B, Tharwat S, Erten S, Nuzzolese R, Karamanakos A, Frassi M, Conforti A, Caggiano V, Marino A, Sebastiani GD, Gidaro A, Tombetti E, Carubbi F, Rubegni G, Cartocci A, Balistreri A, Fabiani C, Frediani B, Cantarini L. Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry. Intern Emerg Med 2023; 18:2231-2243. [PMID: 37828268 PMCID: PMC10635948 DOI: 10.1007/s11739-023-03408-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 08/23/2023] [Indexed: 10/14/2023]
Abstract
To characterize clinical and laboratory signs of patients with Still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. Patients with Still's disease classified according to internationally accepted criteria were enrolled in the AutoInflammatory Disease Alliance (AIDA) Still's Disease Registry. Clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p < 0.001), platelet abnormalities (p < 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p < 0.001). At multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. Clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data.
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Affiliation(s)
- Paola Triggianese
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- University of Rome Tor Vergata, Rome, Italy
| | - Antonio Vitale
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy.
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy.
- Policlinico "Le Scotte", Viale Bracci 1, 53100, Siena, Italy.
| | - Giuseppe Lopalco
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | | | - Francesco Ciccia
- Department of Precision Medicine, Università Degli Studi Della Campania Luigi Vanvitelli, Naples, Italy
| | - Ibrahim Al-Maghlouth
- Rheumatology Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- College of Medicine Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Piero Ruscitti
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Petros Paul Sfikakis
- Joint Academic Rheumatology Program, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Florenzo Iannone
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | | | - Martina Patrone
- Department of Precision Medicine, Università Degli Studi Della Campania Luigi Vanvitelli, Naples, Italy
| | - Kazi Nur Asfina
- College of Medicine Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Ilenia Di Cola
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Katerina Laskari
- Joint Academic Rheumatology Program, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Carla Gaggiano
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy
| | - Abdurrahman Tufan
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Paolo Sfriso
- Rheumatology Unit, Department of Medicine (DIMED), University of Padova, Padua, Italy
| | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Roberto Giacomelli
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policlinico Campus Bio-Medico, Via Álvaro del Portillo 200, 00128, Rome, Italy
- Rheumatology and Clinical Immunology, Department of Medicine, School of Medicine, University of Rome "Campus Biomedico", Rome, Italy
| | - Andrea Hinojosa-Azaola
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Gaafar Ragab
- Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
- Faculty of Medicine, Newgiza University, 6th of October City, Egypt
| | - Lampros Fotis
- Third Department of Paediatrics, National and Kapodistrian University of Athens, General University Hospital "Attikon", Athens, Greece
| | - Haner Direskeneli
- Department of Internal Medicine, Division of Rheumatology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Veronica Spedicato
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Marilia Ambiel Dagostin
- Rheumatology Division, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, Brazil
| | - Daniela Iacono
- Department of Precision Medicine, Università Degli Studi Della Campania Luigi Vanvitelli, Naples, Italy
| | - Hebatallah Hamed Ali
- College of Medicine Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Paola Cipriani
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Jurgen Sota
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy
| | - Riza Can Kardas
- Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Sara Bindoli
- Rheumatology Unit, Department of Medicine (DIMED), University of Padova, Padua, Italy
| | - Corrado Campochiaro
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Luca Navarini
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policlinico Campus Bio-Medico, Via Álvaro del Portillo 200, 00128, Rome, Italy
- Rheumatology and Clinical Immunology, Department of Medicine, School of Medicine, University of Rome "Campus Biomedico", Rome, Italy
| | - Stefano Gentileschi
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy
| | - Eduardo Martín-Nares
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jiram Torres-Ruiz
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Moustafa Ali Saad
- Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Katerina Kourtesi
- Third Department of Paediatrics, National and Kapodistrian University of Athens, General University Hospital "Attikon", Athens, Greece
| | - Fatma Alibaz-Oner
- Department of Internal Medicine, Division of Rheumatology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Gizem Sevik
- Department of Internal Medicine, Division of Rheumatology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Annamaria Iagnocco
- Academic Rheumatology Center, Dipartimento Scienze Cliniche e Biologiche, Università degli Studi di Torino, Turin, Italy
| | - Joanna Makowska
- Department of Rheumatology, Medical University of Lodz, Lodz, Poland
| | - Marcello Govoni
- Rheumatology Unit, Department of Medical Sciences, Azienda Ospedaliero-Universitaria S. Anna-Ferrara, University of Ferrara, Ferrara, Italy
| | - Sara Monti
- Rheumatology Department, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Fondazione, University of Pavia, Pavia, Italy
| | - Maria Cristina Maggio
- University Department Pro.Sa.M.I. "G. D'Alessandro", University of Palermo, Palermo, Italy
| | | | - Emanuela Del Giudice
- Pediatric and Neonatology Unit, Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Polo Pontino, Latina, Italy
| | - José Hernández-Rodríguez
- Vasculitis Research Unit and Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Barcelona, Spain
| | - Elena Bartoloni
- Department of Medicine and Surgery, MED/16- Rheumatology, Università degli Studi di Perugia, P.Zza Università, 06123, Perugia, Italy
| | - Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Melbourne, Australia
| | - Maria Sole Chimenti
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Armin Maier
- Rheumatology Unit, Department of Medicine, Central Hospital of Bolzano, Bolzano, Italy
| | - Gabriele Simonini
- NEUROFARBA Department, Rheumatology Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Giovanni Conti
- Pediatric Nephrology and Rheumatology Unit, AOU Policlinic G Martino, Messina, Italy
| | - Alma Nunzia Olivieri
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Tarsia
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy
| | - Amato De Paulis
- Section of Clinical Immunology, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Department of Translational Medical Sciences, Center for Basic and Clinical Immunology Research (CISI), World Allergy Organisation Center of Excellence, University of Naples Federico II, Naples, Italy
| | - Alberto Lo Gullo
- Unit of Rheumatology, Department of Medicine, ARNAS Garibaldi Hospital, Catania, Italy
| | - Ewa Więsik-Szewczyk
- Department of Internal Medicine, Pulmonology, Allergy and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defence, Military Institute of Medicine, National Research Institute, Warsaw, Poland
| | - Ombretta Viapiana
- Rheumatology Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Benson Ogunjimi
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
- Antwerp Center for Translational Immunology and Virology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Department of Paediatrics, Antwerp University Hospital, Antwerp, Belgium
- Center for Health Economics Research and Modeling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
| | - Samar Tharwat
- Rheumatology and Immunology Unit, Internal Medicine Department, Mansoura University, Mansoura, Egypt
- Department of Internal Medicine, Faculty of Medicine, Horus University, New Damietta, Egypt
| | - Sukran Erten
- Department of Rheumatology, Faculty of Medicine Ankara City Hospital, Ankara Yıldırım Beyazıt University, Ankara, Turkey
| | - Rossana Nuzzolese
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy
| | - Anastasios Karamanakos
- Joint Academic Rheumatology Program, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias Street 75 Goudi, 11527, Athens, Greece
| | - Micol Frassi
- Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Brescia, Italy
| | - Alessandro Conforti
- U.O. Medicina Generale, Ospedale San Paolo di Civitavecchia, ASL Roma 4, Civitavecchia, Rome, Italy
| | - Valeria Caggiano
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy
| | - Achille Marino
- Unit of Pediatric Rheumatology, ASST Gaetano Pini-CTO, Milan, Italy
| | | | - Antonio Gidaro
- Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Enrico Tombetti
- Internal Medicine, Fatebenefratelli Hospital, Milan, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Francesco Carubbi
- Department of Life, Health & Environmental Sciences and Internal Medicine and Nephrology Unit, Department of Medicine, University of L'Aquila and ASL Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | - Giovanni Rubegni
- Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena and Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
| | - Alessandra Cartocci
- Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Alberto Balistreri
- Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Claudia Fabiani
- Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena and Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
| | - Bruno Frediani
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy
| | - Luca Cantarini
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy
- UOC Reumatologia, Azienda Ospedaliero-Universitaria Senese, ERN-RITA Center, Siena, Italy
- Policlinico "Le Scotte", Viale Bracci 1, 53100, Siena, Italy
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Elber-Dorozko S, Kerem L, Wolf D, Brodie S, Berkun Y, Brooks R, Breuer O. Platelet count and risk of severe illness in hospitalised children with Influenza-Like illness. Acta Paediatr 2023; 112:2191-2198. [PMID: 37306590 DOI: 10.1111/apa.16875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 06/01/2023] [Accepted: 06/09/2023] [Indexed: 06/13/2023]
Abstract
AIM To examine the clinical significance of thrombocytosis (platelets > 500 × 109 /L) in admitted children with an influenza-like illness. METHODS We performed a database analysis consisting of patients evaluated at our medical centers with an influenza-like illness between 2009 and 2013. We included paediatric patients and examined the association between platelet count, respiratory viral infections, and admission outcomes (hospital length of stay and admission to the paediatric intensive care unit) using regression models adjusting for multiple variables. RESULTS A total of 5171 children were included in the study cohort (median age 0.8 years; interquartile range, 0.2-1.8; 58% male). Younger age, and not the type of viral infection, was associated with a high platelet count (p < 0.001). Elevated platelet count independently predicted admission outcomes (p ≤ 0.05). The presence of thrombocytosis was associated with an increased risk for a prolonged length of stay (odds ratio = 1.2; 95% Confidence interval = 1.1 to 1.4; p = 0.003) and admission to the paediatric intensive care unit (odds ratio = 1.5; 95% Confidence interval = 1.1 to 2.0; p = 0.002). CONCLUSION In children admitted with an influenza-like illness, a high platelet count is an independent predictor of admission outcomes. Platelet count may be used to improve risk assessment and management decisions in these paediatric patients.
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Affiliation(s)
- Sergei Elber-Dorozko
- Department of Pediatrics, Hadassah Medical Center, and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Liya Kerem
- Department of Pediatrics, Hadassah Medical Center, and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- Division of Pediatric Endocrinology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Dana Wolf
- Clinical Virology Unit, Hadassah Medical Center, and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Shlomit Brodie
- Department of Pediatrics, Hadassah Medical Center, and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Yackov Berkun
- Department of Pediatrics, Hadassah Medical Center, and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Rebecca Brooks
- Department of Pediatrics, Hadassah Medical Center, and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Oded Breuer
- Department of Pediatrics, Hadassah Medical Center, and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- Pediatric Pulmonology and CF Unit, Department of Pediatrics, Hadassah Medical Center, and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
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Zhang L, Chen X, Hu T, Xu Z, Yang W, Fu R, Zhang L, Zhu X. Clinical and molecular characteristics of forty Chinese children with essential thrombocythemia: A single-center, retrospective analysis. Br J Haematol 2023; 201:520-529. [PMID: 36695443 DOI: 10.1111/bjh.18646] [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: 11/11/2022] [Revised: 12/30/2022] [Accepted: 12/30/2022] [Indexed: 01/26/2023]
Abstract
Due to the infrequency of essential thrombocythemia (ET) in children, little is known about its pathophysiological mechanism. To learn about the clinical and molecular features of Chinese children with ET, we retrospectively analysed 40 children with ET in a single center from 2015-2021. More than half of the children (51.3%, 20/39) were asymptomatic at diagnosis. Nearly half of the children (48.7%, 19/39) had microvascular symptoms, including headache, dizziness, stomachache, and paresthesia. Only two cases experienced vascular events. The proportion of children with typical "driver gene mutations" (i.e., JAK2 p.V617F, CALR exon 9, or MPL exon 10 mutation) was low (12.5%, 5/40). The equivalent ratio of children carried atypical driver gene mutations; however, 30 (75%) patients did not harbour driver gene mutations. Children carrying JAK2 p.V617F had lower platelet count (938 × 109 /L vs. 1654 × 109 /L, p = 0.031) compared to those without driver gene mutations. Cases harbouring typical driver mutations had higher median WBC counts than those without driver gene mutations (15.14 × 109 /L vs. 8.01 × 109 /L, p = 0.015). Compared to those without driver gene mutations, cases carrying typical and atypical driver gene mutations were both younger (median ages were 12, 6, and 7 years old, respectively; p = 0.023). The most prevalent non-driver gene mutations and those mutations with prognostic significance in adult counterparts were less common in children with ET compared to adults with ET.
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Affiliation(s)
- Luyang Zhang
- Department of Pediatric Blood Disease Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Xiaoli Chen
- Department of Pediatric Blood Disease Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Tianyuan Hu
- Department of Pediatric Blood Disease Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Zefeng Xu
- MDS and MPN Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Wenyu Yang
- Department of Pediatric Blood Disease Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Rongfeng Fu
- Thrombosis and Hemostasis Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
| | - Lei Zhang
- Thrombosis and Hemostasis Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
| | - Xiaofan Zhu
- Department of Pediatric Blood Disease Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
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Mendes LC, de Oliveira Magalhães R, Pereira Dos Santos RK, Araújo RS. Pseudohypoaldosteronism associated with hypertrophic cardiomyopathy, hypertension and thrombocytosis due to mutation in the ELAC2 gene: a case report. J Pediatr Endocrinol Metab 2022; 35:1437-1442. [PMID: 35946480 DOI: 10.1515/jpem-2021-0626] [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: 11/21/2021] [Accepted: 07/13/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES PHA1 is a rare heterogeneous disorder featured by changes in renal electrolyte transport due to mineralocorticoid resistance. The aim of the current study is to report the case of a child with 5-year follow-up presenting mutation in the ElaC Ribonuclease Z 2 (ELAC2) gene and clinical-laboratory diagnosis of pseudohypoaldosteronism type 1 (PHA1), as well as atypical clinical manifestations such as thrombocytosis, borderline aldosterone levels, and plasma renin activity. CASE PRESENTATION The patient was treated with corticosteroids and salt replenishment. His cardiological condition presented gradual regression and the introduction of new food items in his diet dismissed the need of salt replenishment. CONCLUSIONS This new molecular mechanism should be taken into consideration in differential diagnoses in children with hyperkalemia, hyponatremia, delayed growth, hypertension and hypertrophic cardiomegaly.
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Jeon GW. Pathophysiology, classification, and complications of common asymptomatic thrombocytosis in newborn infants. Clin Exp Pediatr 2022; 65:182-187. [PMID: 34665959 PMCID: PMC8990953 DOI: 10.3345/cep.2021.00864] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 10/18/2021] [Indexed: 11/27/2022] Open
Abstract
We frequently encounter newborn infants with thrombocytosis in the neonatal intensive care unit. However, neonatal thrombocytosis is not yet fully understood. Thrombocytosis is more frequently identified in newborns and young infants, notably more often in those younger than 2 years than in older children or adults. The production of megakaryocytes (megakaryopoiesis) and platelets (thrombopoiesis) is mainly regulated by thrombopoietin (TPO). Increased TPO levels during infection or inflammation can stimulate megakaryopoiesis, resulting in thrombopoiesis. TPO concentrations are higher in newborn infants than in adults. Levels increase after birth, peak on the second day after birth, and start decreasing at 1 month of age. Initial platelet counts at birth increase with gestational age. Thus, preterm infants have lower initial platelet counts at birth than late-preterm or term infants. Postnatal thrombocytosis is more frequently observed in preterm infants than in term infants. A high TPO concentration and low TPO receptor expression on platelets leading to elevated plasma-free TPO, increased sensitivity of megakaryocyte precursor cells to TPO, a decreased red blood cell count, and immaturity of platelet regulation are speculated to induce thrombocytosis in preterm infants. Thrombocytosis in newborn infants is considered a reactive process (secondary thrombocytosis) following infection, acute/chronic inflammation, or anemia. Thrombocytosis in newborn infants is benign, resolves spontaneously, and, unlike in adults, is rarely associated with hemorrhagic and thromboembolic complications.
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Affiliation(s)
- Ga Won Jeon
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
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6
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Clinical implications of thrombocytosis in acute phase Kawasaki disease. Eur J Pediatr 2021; 180:1841-1846. [PMID: 33527178 DOI: 10.1007/s00431-021-03966-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 01/19/2021] [Accepted: 01/25/2021] [Indexed: 10/22/2022]
Abstract
In Kawasaki disease (KD), thrombocytosis is commonly found in the subacute phase. However, the exact significance of thrombocytosis in the acute phase of KD is unclear. To evaluate serum platelet counts in patients during the acute phase of KD and assess the clinical outcomes according to the degree of thrombocytosis, we collected data of KD patients between 2009 and 2017. A total of 505 patients with KD were enrolled, and 249 (49.3%) patients had thrombocytosis, including mild (69.5%), moderate (21.7%), severe (4.8%), and extreme (4.0%) thrombocytosis. Correlation analysis revealed a positive correlation between the maximum platelet count and admission duration (r = 0.359, p < 0.001) and fever duration (r = 0.204, p < 0.001). The maximum platelet count was significantly higher in IVIG non-responders than that in IVIG responders (629 ± 201 × 109/L vs. 499 ± 154 × 109/L, p < 0.001), and in patients with coronary artery dilatation (CAD) than in those without CAD (602 ± 201 × 109/L vs. 512 ± 164 × 109/L, p < 0.001).Conclusion: Thrombocytosis in acute phase KD was associated with poor clinical outcomes such as IVIG non-responsiveness, CAD, and prolonged admission and fever durations. What is Known: • Thrombocytopenia in the acute phase of KD is related to non-responsiveness to IVIG and the risk of coronary artery dilatation. • The exact significance of thrombocytosis in the acute phase of KD as a benign phenomenon or a signal of poor outcome of KD is unclear. What is New: • Thrombocytosis in acute phase KD was associated with poor clinical outcomes such as IVIG non-responsiveness, CAD, and prolonged admission and fever durations.
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Extreme Thrombocytosis after Pediatric Pancreatectomy with Islet Autotransplantation Is Unique Compared to Other Postsplenectomy States. J Pediatr Surg 2020; 55:1645-1650. [PMID: 31677823 DOI: 10.1016/j.jpedsurg.2019.09.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/25/2019] [Accepted: 09/01/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hematologic trends after pancreatectomy with islet autotransplantation (IAT), which involves splenectomy, have been rarely studied. Reactive thrombocytosis (RT, platelets ≥500 K/μL) often occurs postoperatively, similar to other postsplenectomy states, but the degree of similarities and true incidence are unknown. STUDY DESIGN A single-site, retrospective, observational cohort study of patients who underwent total splenectomy between 2010 and 2018 was performed. Thrombocytosis incidence and pharmacologic management strategies were evaluated, including cohort-based analyses for IAT versus other splenectomy indications. RESULTS Analyses included 112 patients overall, 42 of whom underwent IAT. RT occurred frequently (93.8%) despite most patients having normal preoperative platelet counts. IAT patients had significantly higher peak platelet counts compared to non-IAT patients and the rate of platelet rise for IAT patients was significantly faster. IAT was uniquely predictive of developing extreme thrombocytosis (ExT, platelets ≥1000 K/μL, 90% vs. 15.7%, risk ratio 4.11, P < 0.0001) despite standardized hydroxyurea use. Thrombotic events were infrequent and did not differ between groups. CONCLUSIONS RT was common regardless of splenectomy indication but ExT was uniquely associated with IAT despite cytoreductive pharmacotherapy. These results strongly suggest that splenectomy is unlikely to be the sole contributor to post-IAT RT but further investigations into this phenomenon are needed. LEVEL-OF-EVIDENCE RATING Treatment study, Level III (retrospective comparative study).
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Del Rey Hurtado de Mendoza B, Esponera CB, Izquierdo Renau M, Iglesias Platas I. Asymptomatic late thrombocytosis is a common finding in very preterm infants even in the absence of erythropoietin treatment. J Int Med Res 2019; 47:1504-1511. [PMID: 30732496 PMCID: PMC6460626 DOI: 10.1177/0300060518821033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Objectives Thrombocytosis is more prevalent in pediatric than in adult patients and is associated with complications or worsened outcomes after vascular events. This study aimed to determine the prevalence of thrombocytosis in very preterm infants who had not received human recombinant erythropoietin treatment (rHuEPO) and its relationship with other hematological parameters and clinical complications. Methods We performed a retrospective study of hematological and clinical data of very preterm infants who were admitted to our unit in their first 48 hours of life and stayed for longer than 1 week. Results Thrombocytosis was prevalent (32.6% of patients) in very preterm infants (≤32 weeks of gestational age, n = 193) who had not received rHuEPO. The platelet count was positively correlated with calendar age. Infants with thrombocytosis were significantly more premature (28.0 ± 2.1 versus 29.6 ± 2.2 weeks) and had a lower birth weight (1036 ± 304 versus 1303 ± 304) than those without thrombocytosis. Thrombocytosis was associated with retinopathy of prematurity after adjusting for gestational age and comorbidities, but not with other prematurity-associated complications. Conclusions Late asymptomatic thrombocytosis is common in very preterm infants at approximately 1 month of postnatal age and it may be associated with retinopathy of prematurity.
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Affiliation(s)
- Beatriz Del Rey Hurtado de Mendoza
- Neonatal Service, Institut de Recerca Sant Joan de Déu, BCNatal, Hospital Sant Joan de Déu i Clinic, Universitat de Barcelona, C/ Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
| | - Carla Balcells Esponera
- Neonatal Service, Institut de Recerca Sant Joan de Déu, BCNatal, Hospital Sant Joan de Déu i Clinic, Universitat de Barcelona, C/ Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
| | - Montserrat Izquierdo Renau
- Neonatal Service, Institut de Recerca Sant Joan de Déu, BCNatal, Hospital Sant Joan de Déu i Clinic, Universitat de Barcelona, C/ Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
| | - Isabel Iglesias Platas
- Neonatal Service, Institut de Recerca Sant Joan de Déu, BCNatal, Hospital Sant Joan de Déu i Clinic, Universitat de Barcelona, C/ Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
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Abstract
OBJECTIVES The purpose of this article is to review the current literature on drug-induced thrombocytosis with the goal of critically assessing causality and providing a comprehensive review of the topic. Thrombopoietic growth factors, such as thrombopoietin-receptor agonists (romiplostim and eltrombopag) and erythropoietin are not included in our review. DATA SOURCES The literature search included published articles limited to the English language and humans in MEDLINE, EMBASE, and Web of Science databases. MEDLINE/PubMed (1966 to September 2018) was searched using the MeSH terms thrombocytosis/chemically-induced and thrombocytosis/etiology. EMBASE (1980 to September 2018) was searched using the EMTAGS thrombocytosis/side effect. Web of Science (1970 to September 2018) was searched using the search term thrombocytosis. References of all relevant articles were reviewed for additional citations and information. STUDY SELECTION AND DATA EXTRACTION Review articles, clinical trials, background data, case series, and case reports of drug-induced thrombocytosis were collected, and case reports were assessed for causality using a modified Naranjo nomogram. DATA SYNTHESIS Drug-induced thrombocytosis, a form of reactive thrombocytosis cannot be easily differentiated from more common etiologies of reactive thrombocytosis. In all, 43 case reports of drug-induced thrombocytosis from a wide variety of drugs and drug classes were reviewed using a modified Naranjo probability scale that included criteria specific for thrombocytosis. CONCLUSIONS Drug-induced thrombocytosis is a relatively rare adverse drug reaction. The strongest evidence of causality supports low-molecular-weight heparins and neonatal drug withdrawal. Weaker evidence exists for all-trans retinoic acid, antibiotics, clozapine, epinephrine, gemcitabine, and vinca alkaloids.
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Affiliation(s)
- Quyen T Vo
- 1 Southwestern Oklahoma State University, Weatherford, OK, USA
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10
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Shin J, Lee DH, Jung N, Choi HJ, Shim YJ. A cross-sectional retrospective study to analyze the underlying causes and clinical characteristics of children with reactive thrombocytosis at a Korean tertiary medical center. Blood Res 2018; 53:233-239. [PMID: 30310791 PMCID: PMC6170300 DOI: 10.5045/br.2018.53.3.233] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 06/04/2018] [Accepted: 06/26/2018] [Indexed: 12/18/2022] Open
Abstract
Background Reactive thrombocytosis (RT) is a common condition among children, although no studies have examined the etiology or clinical characteristics of RT among Korean children. Methods This retrospective study evaluated children with RT at a single Korean tertiary center during a 10-year period. Results RT accounted for 13.5% of children who were admitted to the pediatric ward (4,113/30,355): mild RT, 82.7%; moderate RT, 14.1%; severe RT, 1.1%; and extreme RT, 2.1%. There was a negative correlation between platelet count and Hb level (P=0.008). There were positive correlations between platelet count and WBC (P=0.001), erythrocyte sedimentation rate (ESR) (P=0.007), and admission duration (P=0.006). The most common cause of RT was infection and the second most common was Kawasaki disease (KD). The highest proportion of lower respiratory tract infection was observed in extreme RT (P<0.001). The proportion of KD was highest in extreme RT (P<0.001) and in children aged 1–7.9 years (P<0.001). The proportion of refractory KD was highest in extreme RT (P=0.005). In cases of KD, there was a positive correlation between platelet count and fever duration (P=0.006). Non-KD autoimmune inflammation was only observed in mild/moderate RT, and its proportion was highest in children aged 8–18 years (P<0.001). Conclusion In children, more severe RT was associated with lower Hb, increased WBC, ESR, and prolonged admission. With respiratory infection or KD, extreme RT was associated with more severe disease course.
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Affiliation(s)
- Juhee Shin
- Department of Pediatrics, Keimyung University School of Medicine and Dongsan Medical Center, Daegu, Korea
| | - Dong Hyun Lee
- Department of Pediatrics, Keimyung University School of Medicine and Dongsan Medical Center, Daegu, Korea
| | - Nani Jung
- Department of Pediatrics, Keimyung University School of Medicine and Dongsan Medical Center, Daegu, Korea
| | - Hee Joung Choi
- Department of Pediatrics, Keimyung University School of Medicine and Dongsan Medical Center, Daegu, Korea
| | - Ye Jee Shim
- Department of Pediatrics, Keimyung University School of Medicine and Dongsan Medical Center, Daegu, Korea
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11
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Al Shibli A, Alkuwaiti N, Hamie M, Abukhater D, Noureddin MB, Amri A, Al Kaabi S, Al Kaabi A, Harbi M, Narchi H. Significance of platelet count in children admitted with bronchiolitis. World J Clin Pediatr 2017; 6:118-123. [PMID: 28540196 PMCID: PMC5424280 DOI: 10.5409/wjcp.v6.i2.118] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 08/11/2016] [Accepted: 11/22/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the true prevalence of thrombocytosis in children less than 2 years of age with bronchiolitis, its association with risk factors, disease severity and thromboembolic complications.
METHODS A retrospective observational medical chart review of 305 infants aged two years or less hospitalized for bronchiolitis. Clinical outcomes included disease severity, duration of hospital stay, admission to pediatric intensive care unit, or death. They also included complications of thrombocytosis, including thromboembolic complications such as cerebrovascular accident, acute coronary syndrome, deep venous thrombosis, pulmonary embolus, mesenteric thrombosis and arterial thrombosis and also hemorrhagic complications such as bleeding (spontaneous hemorrhage in the skin, mucous membranes, gastrointestinal, respiratory, or genitourinary tracts).
RESULTS The median age was 4.7 mo and 179 were males (59%). Respiratory syncytial virus was isolated in 268 (84%), adenovirus in 23 (7%) and influenza virus A or B in 13 (4%). Thrombocytosis (platelet count > 500 × 109/L) occurred in 88 (29%; 95%CI: 24%-34%), more commonly in younger infants with the platelet count declining with age. There was no significant association with the duration of illness, temperature on admission, white blood cell count, serum C-reactive protein concentration, length of hospital stay or admission to the intensive care unit. No death, thrombotic or hemorrhagic events occurred.
CONCLUSION Thrombocytosis is common in children under two years of age admitted with bronchiolitis. It is not associated with disease severity or thromboembolic complications.
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12
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Xuemei Z, Yongshu D, Ling Z, Yingying Y, Ping F. Extreme Thrombocytosis Presenting in Anti-Neutrophil Cytoplasmic Autoantibodies-Associated Crescentic Glomerulonephritis with Immune Complex Deposits: A Case Report. IRANIAN RED CRESCENT MEDICAL JOURNAL 2017; 18:e23272. [PMID: 28180010 PMCID: PMC5285513 DOI: 10.5812/ircmj.23272v2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/16/2014] [Accepted: 03/20/2015] [Indexed: 02/05/2023]
Abstract
INTRODUCTION We describe a female patient with extreme reactive thrombocytosis (RT) in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated crescentic glomerulonephritis (CGN) with immune complex deposits, which has never been reported before. CASE PRESENTATION A female adolescent with symptoms of oliguria and gross hematuresis had serious renal function impairment (crescent formation and immune complex deposits in renal pathology examination with positive serum ANCA) and extreme thrombocytosis. We made a diagnosis of CGN and RT. After treatment with Prednisone, Cyclophosphamide, and plasmapheresis, the symptoms of oliguria and gross hematuresis were relieved remarkably and the serum creatinine and platelet count declined significantly. CONCLUSIONS The diagnosis of thrombocytosis is not easy in all cases. The coexistence of ANCA and the immune complex in CGN may cause a severe inflammatory state, leading to extreme RT. The roles that the immune complex and ANCA play on the effect of the platelet count and function in CGN need further research.
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Affiliation(s)
- Zhang Xuemei
- Division of Nephrology, West China Hospital, Sichuan University, Chengdu, China
| | - Diao Yongshu
- Division of Nephrology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhang Ling
- Division of Nephrology, West China Hospital, Sichuan University, Chengdu, China
| | - Yang Yingying
- Division of Nephrology, West China Hospital, Sichuan University, Chengdu, China
| | - Fu Ping
- Division of Nephrology, West China Hospital, Sichuan University, Chengdu, China
- Corresponding Author: Fu Ping, Division of Nephrology, West China Hospital, Sichuan University, Chengdu, China. Tel: +86-18980601201, Fax: +86-28 85421085, E-mail:
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Singh A, Nityanand S, Sonker A, Kumar S. Successful use of the cell separator hemonetics multicomponent collection system+ for therapeutic thrombocytapheresis in a low body weight child of essential thrombocythemia. Asian J Transfus Sci 2015; 9:207-9. [PMID: 26420947 PMCID: PMC4562148 DOI: 10.4103/0973-6247.162722] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
In children, essential thrombocythemia (ET) is extremely rare with an incidence of 1/million. Since thromboembolic complications are more common than hemorrhagic manifestation, immediate thromboctyapheresis by an automated cell separator can prevent untoward consequences in the form of cerebrovascular, coronary or peripheral vascular occlusive events. Due to varied options of automated cell separators, selecting an appropriate cell separator in such acute emergency situation can be confusing for a treating physician, especially if the patient is a child of low body weight. We present here the successful use of hemonetics multicomponent collection system (MCS+) for therapeutic platelet reduction (TPR) in a 12-year-old male child of 28 kg with extreme thrombocytosis (TS) (3072 × 109/l) due to ET. A total of three procedures were performed without priming of the machine with allogenic blood. We observed hemonetics MCS+, best suited for TPR even in children with low body weight.
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Affiliation(s)
- Abhay Singh
- Department of Transfusion Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Soniya Nityanand
- Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Atul Sonker
- Department of Transfusion Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Sanjeev Kumar
- Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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14
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Bertrand A, Heissat S, Caron N, Viremouneix L, Pracros JP, Javouhey E, Lachaux A, Mialou V. [Deep vein thrombosis revealing myeloproliferative syndrome in two adolescents]. Arch Pediatr 2014; 21:497-500. [PMID: 24709317 DOI: 10.1016/j.arcped.2014.02.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Revised: 09/05/2013] [Accepted: 02/06/2014] [Indexed: 10/25/2022]
Abstract
Deep vein thrombosis occurs in 30% of patients with essential thrombocythemia, but rarely at initial diagnosis. We report two pediatric patients with essential thrombocythemia revealed by atypical deep vein thrombosis. First, a 16-year-old girl presented Budd-Chiari syndrome revealed by a hemorrhagic shock. Clinical exam revealed isolated splenomegaly. A search for thrombophilia found a factor V Leiden homozygous mutation and a Jak2 mutation. Bone marrow biopsy confirmed the diagnosis of a myeloproliferative disorder. The second case, a 17-year-old girl, had a routine examination by her physician that revealed splenomegaly. Ultrasonography displayed thrombus in the splenic and portal vein. An isolated Jak2 mutation was found and a myeloproliferative disorder was confirmed by bone marrow biopsy. The diagnosis of myeloproliferative disorder was made in both patients presenting atypical venous thrombosis with a Jak2 mutation and confirmed by bone marrow biopsy. These initial presentations of myeloproliferative disorders are rare in childhood and possibly underdiagnosed.
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Affiliation(s)
- A Bertrand
- Institut d'hématologie et d'oncologie pédiatrique, 2, place Joseph-Renault, 69008 Lyon, France.
| | - S Heissat
- Gastro-entérologie, hôpital-Femme-Mère Enfant, 69500 Bron, France
| | - N Caron
- Urgences Pédiatriques, CHU d'Estaing, Clermont-Ferrand, France
| | | | - J-P Pracros
- Radiologie, hôpital Femme-Mère-Enfant, Lyon, France
| | - E Javouhey
- Réanimation pédiatrique, hôpital Femme-Mère-Enfant, Lyon, France
| | - A Lachaux
- Gastro-entérologie, hôpital-Femme-Mère Enfant, 69500 Bron, France
| | - V Mialou
- Banque de tissus et cellules, établissement français du sang, hôpital Édouard-Herriot, Lyon, France
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15
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Two cases of pediatric essential thrombocythemia managed effectively with hydroxyurea. Int J Hematol 2012; 96:810-3. [PMID: 23054653 DOI: 10.1007/s12185-012-1193-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2012] [Revised: 09/21/2012] [Accepted: 09/24/2012] [Indexed: 10/27/2022]
Abstract
Thrombocytosis is common in infancy and childhood. Essential thrombocythemia (ET), a myeloproliferative disorder, is a much less common cause of thrombocytosis in childhood. We report two cases of essential thrombocythemia in 5- and 10-year-old children, who presented with platelet counts of more than 1,000,000/mm(3). Treatment is not recommended for ET in an asymptomatic patient in the absence of bleeding or thrombosis and a platelet count <1,500,000/mm(3). Our first case had platelets >1,500,000/mm(3), and a second child was symptomatic with recurrent headache. Both responded well to therapy with hydroxyurea (dose 15-30 mg/kg/day) and tolerated it well.
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16
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Wang JL, Huang LT, Wu KH, Lin HW, Ho MY, Liu HE. Associations of reactive thrombocytosis with clinical characteristics in pediatric diseases. Pediatr Neonatol 2011; 52:261-6. [PMID: 22036221 DOI: 10.1016/j.pedneo.2011.06.004] [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] [Received: 06/08/2010] [Revised: 10/04/2010] [Accepted: 10/22/2010] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Reactive thrombocytosis (RT) in pediatric patients is common, but usually without symptoms. The incidence of RT is different depending on age. Mostly, we reason that RT is a phenomenon, nevertheless the diagnostic value of RT is little known. Therefore, the aim of this study was to determine the association of RT and clinical or laboratory characteristics in pediatric diseases. METHODS We retrospectively analyzed the medical records of pediatric patients hospitalized at Wan Fang hospital from January 2002 to July 2009. Thrombocytosis was defined as a platelet count more than 500 × 10(9)/L. There were 822 patients enrolled to this study. The clinical parameters, including age, gender, disease type, and hospitalization days, were investigated. The association between RT and clinical manifestations and the relationship of leukocytes, hemoglobin, C-reactive protein, and platelet counts were analyzed. RESULTS The overall incidence of RT in hospitalized pediatric patients was 6.3%. Infants had a significantly higher incidence (11.3%, p<0.001). Mild RT was found in most patients (83.6%). Infections (75.4%) were the most common cause, followed by perinatal diseases (11.1%). The relationship of RT and age revealed a positive correlation (p=0.045, r=0.70 after adjustment). The degree of RT was an independent factor for hospitalization days (p<0.001, r=0.126 after adjustment). There was a positive correlation between white blood cell count and platelets (p=0.002, r=0.017); on the contrary, the relationship between hemoglobin level and platelets was an inverse correlation (p<0.001, r=-0.193). CONCLUSIONS In children, the degree of RT was associated with age, and patients had significantly longer hospitalization days in proportion to the increase in platelet count. Laboratory association revealed that the degree of RT was positively correlated to white cell count and negatively correlated to hemoglobin level. Therefore, the degree of RT might be a predictive factor with regard to hospitalization days in pediatric diseases.
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Affiliation(s)
- Jinn-Li Wang
- Department of Pediatrics, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
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Wiedmeier SE, Henry E, Burnett J, Anderson T, Christensen RD. Thrombocytosis in neonates and young infants: a report of 25 patients with platelet counts of > or = 1000000 microl(-1). J Perinatol 2010; 30:222-6. [PMID: 19798040 DOI: 10.1038/jp.2009.146] [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: 01/28/2023]
Abstract
OBJECTIVE Thrombocytosis has been reported in neonates and young infants, but little is known of its prevalence, timing of onset, associated conditions, sequelae and outcomes. To better understand this condition, we used the data repositories of a multi-hospital health-care system to identify all individuals <or=140 days old (20 weeks) who, during the past 6 years, had a platelet count of >or=1000000 microl(-1). STUDY DESIGN We identified all infants with extreme thrombocytosis (using the Sutor definition of a platelet count of >or=1000000 microl(-1)) during the period of January 2003 through December 2008 in any Intermountain Healthcare facility. We obtained the information provided in this report from electronic and paper records. RESULT Among 40 471 infants who had one or more platelet counts performed in this period, 25 had extreme thrombocytosis. No cases were identified in the first week after birth, 40% were recognized between the second and fourth weeks and 40% between the fifth and eighth week. The prevalence of thrombocytosis had no relationship with birth weight or gestational age but a slight predominance of female patients (15/25) was noted. In all, 26 episodes were found among the 25 infants: 12 episodes involved an antecedent infectious disease, 8 had an antecedent surgical procedure, 4 had the anemia of prematurity and 1 each had congenital adrenal hyperplasia and opiate withdrawal syndrome. No pathological thromboses or hemorrhages or other sequelae were detected and all episodes resolved with no deaths. CONCLUSION The thrombocytosis cases that we report were all consistent with reactive thrombocytosis (also known as secondary thrombocytosis); none seemed to be essential (primary) thrombocytosis. We speculate that the pathogenesis involves increased platelet production due to megakaryopoietic stimulators induced by an infectious or inflammatory condition. From this series and previous reports, young infants with platelet counts up to 1300000 microl(-1) do not seem to have a significant risk of thrombotic or hemorrhagic problems, and do not generally require anti-platelet or cytoreductive treatment.
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Affiliation(s)
- S E Wiedmeier
- Department of Women and Newborns, Intermountain Healthcare, Salt Lake City, UT 84157-7000, USA.
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18
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Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 2009; 29:130-6. [PMID: 18818663 DOI: 10.1038/jp.2008.141] [Citation(s) in RCA: 125] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Identifying a platelet count as abnormal (thrombocytopenia or thrombocytosis) can facilitate recognizing various disease states. However, the published reference ranges for platelet counts in neonates may be imprecise, as they were generated from relatively small sample sizes and compiled before modern platelet enumeration methods. STUDY DESIGN We derived new neonatal reference ranges for platelet counts and mean platelet volume (MPV) measurements using electronic data accumulated during a recent 6-year period from a multihospital healthcare system. RESULT Platelet counts were obtained between the first and the 90th day after birth, from 47,291 neonates delivered at 22 to 42 weeks gestation. The first platelet counts obtained in the first 3 days of life, increased over the range of 22 to 42 weeks gestation. In those born < or =32 weeks gestation, the lower reference range (5th percentile) was 104,200 microl(-1), but it was 123,100 microl(-1) in late-preterm and -term neonates. Advancing postnatal age had a significant effect on platelet counts; during the first 9 weeks, the counts fit a sinusoidal pattern with two peaks; one at 2 to 3 weeks and a second at 6 to 7 weeks. The upper limit of expected counts (95th percentile) during these peaks were as high as 750,000 microl(-1). CONCLUSION The figures herein describe reference ranges for platelet counts and MPV determinations of neonates at various gestational ages during their first 90 days. Expected values differ substantially from the 150,000 microl(-1) to 450,000 microl(-1) range previously used to define neonatal thrombocytopenia and thrombocytosis. The new definitions will render the diagnoses of neonatal thrombocytopenia and thrombocytosis less commonly than when the old definitions were used, because the new ranges are wider than 150,000 microl(-1) to 450,000 microl(-1).
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Abstract
Thrombocytosis in childhood is not rare but essential thrombocythemia is an extremely rare myeloproliferative disorder in childhood. The authors report a case of essential thrombocythemia in an 8-year-old boy who was diagnosed during further evaluation of an incidental finding of thrombocythemia in a school health examination.
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Affiliation(s)
- Jayoung Hwang
- The Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Mialou V, Kagialis-Girard S, Galambrun C, Pondarré C, Kebaili K, Ffrench M, Pagès MP, Bertrand Y. [Thrombocytosis and essential thrombocythemia in childhood]. Arch Pediatr 2005; 12:1249-54. [PMID: 15908186 DOI: 10.1016/j.arcped.2005.04.072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2004] [Accepted: 04/14/2005] [Indexed: 10/25/2022]
Abstract
Thrombocytosis is frequently observed in pediatric patients. Among them the secondary thrombocytosis are the most frequent and result from several causes. The rarely primary thrombocytosis can be either constitutive (and often familial) or acquired (essential thrombocythemia). The purpose of this article is to give diagnostic orientation and to suggest which biological tests should be performed.
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Affiliation(s)
- V Mialou
- Service d'hématologie pédiatrique, hôpital Debrousse, 27, rue Soeur-Bouvier, 69005 Lyon, France.
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21
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Abstract
This review summarizes current data on the pathomechanisms and clinical aspects of primary and secondary thrombocytosis in childhood. Primary thrombocytosis is extremely rare in childhood, mostly diagnosed at the beginning of the second decade of life. As in adults, the criteria of the Polycythemia Vera Group are appropriate to diagnose primary thrombocytosis. The pathomechansims of non-familial forms are complex and include spontaneous formation of megakaryopoietic progenitors and increased sensitivity to thrombopoietin (Tpo). Familial forms can be caused by mutations in Tpo or Tpo receptor (c-mpl) genes. These mutations result in overexpression of Tpo, sustained intracellular signalling or disturbed regulation of circulating Tpo. Treatment of primary thrombocytosis is not recommended if platelet counts are <1500/nl and bleeding or thrombosis did not occur in patient's history. In severe cases, decision on treatment should weigh potential risks of treatment options (hydroxyurea, anagrelide) against expected benefits for preventing thrombosis or haemorrhage. Secondary thrombocytosis is frequent in children, in particular in the first decade of life. Hepatic Tpo production is stimulated in acute response reaction to a variety of disorders. Thrombosis prophylaxis is not required, even at platelet counts >1000/nl, except for cases with additional prothrombotic risk factors.
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Affiliation(s)
- Christof Dame
- Department of Neonatology, Charité- University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
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22
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Abstract
The myeloproliferative disorder, essential thrombocythaemia (ET), is extremely rare in children. In adults, thrombosis is the most common complication whereas a low number of children develop thrombosis and/or haemorrhages. Diagnosis of ET is often difficult, but identifying ET from other causes of thrombocytosis is essential, otherwise therapy may be ineffective as the wrong disease will be treated. Only anecdotal experiences have been published with regard to the treatment of paediatric ET. A watch-and-wait strategy seems appropriate in asymptomatic cases and low-dose aspirin should be used to reduce microvascular disturbances. Anagrelide or IFNs may be considered as first-line, and hydroxyurea as second-line therapy. Anagrelide may become the treatment of choice for ET in children if a lack of leukaemogenic potential is confirmed.
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23
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Abstract
OBJECTIVE We sought to identify changes in platelet (PLT) counts over time, and to evaluate the patterns of thrombocytopenia and thrombocytosis in hospitalized infants 23.8 weeks to term gestation. STUDY DESIGN Neonates were divided into four gestational age groups and their PLT counts were retrospectively compared for prevalence of thrombocytopenia, thrombocytosis, and associated conditions. RESULTS Postconceptional age, postnatal age, and sepsis (among other factors) affected PLT counts. When counts from noninfected appropriately grown infants were evaluated, the risk of thrombocytopenia and thrombocytosis were highest in the most preterm infants, and these risks changed with corrected gestational age. PLT counts increased weekly over the first 4 weeks of life for all but the most preterm infants. CONCLUSIONS These data characterize the incidence of thrombocytopenia and thrombocytosis across a wide range of gestational ages and show that, even in noninfected neonates, these conditions are common, and risk decreases with increasing maturity. The age-related changes in PLT patterns may reflect maturation of platelet regulation.
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Affiliation(s)
- Ronald J McPherson
- Department of Pediatrics/Neonatology, University of Washington, Seattle, WA 98195-6320, USA
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24
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Nakayama H, Ihara K, Hikino S, Yamamoto J, Nagatomo T, Takemoto M, Hara T. Thrombocytosis in preterm infants: a possible involvement of thrombopoietin receptor gene expression. J Mol Med (Berl) 2005; 83:316-20. [PMID: 15647951 DOI: 10.1007/s00109-004-0619-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2004] [Accepted: 11/01/2004] [Indexed: 11/29/2022]
Abstract
Transient thrombocytosis is commonly observed in preterm infants after birth, but its physiological mechanism is still unknown. To understand the mechanism of the transient thrombocytosis in preterm infants we firstly evaluated a correlation between platelet counts and thrombopoietin (TPO) levels in preterm infants and next c-mpl mRNA levels on platelets in healthy preterm infants longitudinally during a half-year of life. The mean platelet counts in 45 very low birth weight infants (mean gestational age 27.4+/-1.8 weeks, mean birth weight 1047+/-249 g) was 230+/-71x10(9)/l just after birth and thereafter gradually increased to 579+/-178x10(9)/l by 5 weeks of age. The platelet counts continued this level for about next 8 weeks. Serum TPO levels soon after birth and at 1 month of age were significantly higher than those at the age of 2-6 months. There was a significant negative correlation between platelet counts and serum TPO values. The c-mpl expression levels on platelets at birth and at 1 month of age tended to be lower than those on platelets from adults, and the c-mpl levels gradually increased through 6 months of age, although they were still lower than those of adults. Our results suggest that low expression of TPO receptor on platelets until 1 month after birth cause a decreased TPO clearance and keep a high level of free TPO in blood, thereby promoting platelet production from megakaryocytes or their progenitors in bone marrow, resulting in the subsequent thrombocytosis in preterm infants.
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Affiliation(s)
- Hideki Nakayama
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, 812-8582 Fukuoka, Japan
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25
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Affiliation(s)
- Paul T Jubinsky
- Section of Pediatric Hematology/Oncology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
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26
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Benedict SL, Bonkowsky JL, Thompson JA, Van Orman CB, Boyer RS, Bale JF, Filloux FM. Cerebral sinovenous thrombosis in children: another reason to treat iron deficiency anemia. J Child Neurol 2004; 19:526-31. [PMID: 15526958 DOI: 10.1177/08830738040190070901] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Iron deficiency anemia is a rare cause of cerebral sinovenous thrombosis in children. We report three cases of cerebral sinovenous thrombosis and iron deficiency anemia treated at Primary Children's Medical Center in Salt Lake City, Utah, between 1998 and 2001. The children were 9, 19, and 27 months old at the time of admission. Hemoglobin levels ranged from 6.6 to 7.0 g/dL, mean corpuscular volume levels from 45 to 56 fL, and platelet counts from 248,000 to 586,000/microL. Magnetic resonance imaging and magnetic resonance venography revealed thrombosis of the straight sinus and internal cerebral veins in all three children, with the addition of the vein of Galen, left transverse and sigmoid sinuses, and upper left internal jugular vein in one child. Recovery ranged from excellent to poor in 3 months to 3 years of follow-up. Four additional cases, ages 6 to 22 months, were found in the English-language literature. Evaluation for prothrombotic disorders was negative in all children, including the current cases. Treatments have included thrombectomy, corticosteroids, mannitol, heparin, low-molecular-weight heparin, warfarin, aspirin, blood transfusion, and iron supplementation, but there is no consensus regarding therapy, other than to correct the anemia and treat iron deficiency. Iron deficiency anemia, a preventable cause of cerebral sinovenous thrombosis, deserves consideration when cerebral sinovenous thrombosis is detected in young children.
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Affiliation(s)
- Susan L Benedict
- Division of Pediatric Neurology, Department of Pediatrics, The University of Utah and Primary Children's Medical Center, Salt Lake City, UT 84113, USA.
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27
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Abstract
Essential thrombocythemia is a distinct clinical entity within the spectrum of myeloproliferative disorders. There is as yet no pathognomonic diagnostic test, and patients who currently fall into the category of essential thrombocythemia are likely to be heterogeneous. This article discusses diagnostic criteria, clinical features, prognosis, and management.
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Affiliation(s)
- Claire N Harrison
- Department of Haematology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
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28
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Florensa L, Zamora L, Besses C, Ortega JJ, Bastida P, Toll T, Mayayo P, Espinet B, Solé F, Serrano S, Woessner S. Cultures of myeloid progenitor cells in pediatric essential thrombocythemia. Leukemia 2002; 16:1876-7. [PMID: 12200712 DOI: 10.1038/sj.leu.2402574] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2002] [Accepted: 03/28/2002] [Indexed: 11/08/2022]
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29
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Kuo YR, Yang KD, Yang MY, Huang MNL, Lin CW, Lin FC, Wei FC, Jeng SF. Reactive thrombocytosis alone does not affect the patency of microvascular anastomosis in the splenectomy rat. Plast Reconstr Surg 2002; 110:812-7. [PMID: 12172143 DOI: 10.1097/00006534-200209010-00014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Vascular thrombosis is a harbinger of failure in microsurgery. However, there is still controversy regarding the correlation of the complications of thrombocytosis and thrombosis. Some evidence indicates that patients with elevated platelet counts tend to have a higher flap failure rate, and surgeons usually hesitate to operate on patients with thrombocytosis. Nevertheless, the authors have experienced successful free tissue transfer in seven patients with thrombocytosis resulting from traumatic splenectomy or multiple trauma. On the basis of clinical observation, the authors investigated whether reactive thrombocytosis contributes to the patency of a microvascular anastomosis. In a rodent splenectomy-induced thrombocytosis model (n = 40), stable reactive thrombocytosis occurred after postoperative days 5 to 10, with the peak on postoperative day 7. Femoral artery division and reanastomosis was performed in rats with or without splenectomy-induced thrombocytosis, and vascular patency was assessed. Platelet counts and platelet activation were studied in correlation to microvascular patency. Platelet activation as demonstrated by CD62P expression on platelets was not significantly different between rats with and without thrombocytosis (6.41 +/- 0.95 percent versus 4.51 +/- 0.55 percent, respectively; p = 0.089). As immature platelets were not increased (2.86 +/- 0.33 percent versus 1.99 +/- 0.32 percent, p = 0.074), it seems that the splenectomy-induced thrombocytosis is the result of redistribution of platelets instead of an increase in bone marrow production. There were no significant differences in the patency rates or perfusion units of femoral artery after arterial anastomosis between rats with and without thrombocytosis (90 percent and 95 percent, respectively; p = 0.561). In conclusion, this study demonstrates that microvascular anastomosis can be performed safely in patients with reactive thrombocytosis without platelet activation.
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Affiliation(s)
- Yur-Ren Kuo
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital Kaohsiung, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan
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30
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Ishiguro A, Suzuki Y, Mito M, Shimbo T, Matsubara K, Kato T, Miyazaki H. Elevation of serum thrombopoietin precedes thrombocytosis in acute infections. Br J Haematol 2002; 116:612-8. [PMID: 11849220 DOI: 10.1046/j.0007-1048.2001.03304.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
To clarify the mechanisms underlying thrombocytosis secondary to infections, we longitudinally studied serum levels of thrombopoietin (TPO) and interleukin (IL)-6 in 15 infants and young children with prominent thrombocytosis (platelets >700 x 10(9)/l) following acute infections and 116 age-matched controls using an enzyme-linked immunosorbent assay. The subjects included nine patients with bacterial infections, three with viral infections and three with non-determined pathogens. TPO values in the controls were 2.24 +/- 0.87 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85-4.47 fmol/ml. In the first week of infection, platelet counts were normal, but TPO values increased (approximately 10.73 fmol/ml). TPO levels peaked on day 4 +/- 2 at 6.44 +/- 2.37 fmol/ml and then fell gradually. When platelet counts peaked in the second and third weeks, TPO levels were similar to the controls. IL-6 levels in the first week rose and dropped more rapidly than TPO. Serum TPO values were significantly correlated with C-reactive protein levels (r = 0.688, P < 0.001) and IL-6 levels (r = 0.481, P = 0.027). These results suggest that TPO contributes to thrombocytosis following infections in conjunction with IL-6, arguing for additional regulatory mechanisms of blood TPO levels.
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Affiliation(s)
- Akira Ishiguro
- Department of Paediatrics, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan.
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31
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Randi ML, Putti MC, Fabris F, Sainati L, Zanesco L, Girolami A. Features of essential thrombocythaemia in childhood: a study of five children. Br J Haematol 2001; 108:86-9. [PMID: 10651728 DOI: 10.1046/j.1365-2141.2000.01817.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Essential thrombocythaemia (ET) is usually considered a disease of the middle-aged but, with the advent of automated platelet counting, ET is diagnosed with increasing frequency in young adults and, even more rarely, in children. We report five paediatric patients (four girls and one boy, mean age 89 months) diagnosed with ET in agreement with Polycythaemia Vera Study Group criteria. The patients had a persistent thrombocytosis over 900 x 10(9)/l and, at the time of diagnosis, their platelet count ranged between 1,112 and 3,178 x 10(9)/l. A 9-month-old girl had thrombosis of the inferior cava vein, two children had headaches and two others remained asymptomatic throughout the follow-up period. Megakaryocytes in the bone marrow were increased in number. The chromosomal analysis was normal, and bcr rearrangement was always negative. None of the patients had spontaneous BFU-E or altered levels of serum erythropoietin and thrombopoietin. Two patients showed alteration of platelet aggregation, and all had decreased levels of intraplatelet serotonin. In spite of the diagnosis of ET in our patients, we are not sure that the cases reported here are really myeloproliferative disorders. The features could suggest that the cases observed may be affected by an 'idiopathic thrombocytosis' without myeloproliferation. Possible variants of ET are described in young adults, and the heterogeneous nature of ET is also suggested by our paediatric patients. Only careful long-term follow-up of patients such as these will clarify the natural history of these disorders and suggest therapeutic management.
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Affiliation(s)
- M L Randi
- Department of Medical and Surgical Science, University of Padua Medical School, Italy
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32
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Matsubara K, Baba K, Nigami H, Harigaya H, Ishiguro A, Kato T, Miyazaki H. Early elevation of serum thrombopoietin levels and subsequent thrombocytosis in healthy preterm infants. Br J Haematol 2001; 115:963-8. [PMID: 11843834 DOI: 10.1046/j.1365-2141.2001.03183.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
To verify pathophysiological mechanisms underlying thrombocytosis in low-birth-weight (LBW) preterm babies, we evaluated kinetic changes in platelet counts and thrombopoietic cytokines including thrombopoietin (TPO), interleukin 6 (IL-6) and IL-11 in 24 uncomplicated preterm infants. Platelet counts in cord blood (CB) (265 +/- 64 x 10(9)/l) were similar to adult levels, increased by d 14 (473 +/- 140 x 10(9)/l), and then remained fairly constant. Thrombocytosis (> 500 x 10(9)/l) was observed in 9/24 (38%) subjects. Mean TPO level in CB was 5.11 +/- 1.51 fmol/ml, peaked at d 2 (7.64 +/- 3.28 fmol/ml), decreased at d 5 (3.93 +/- 1.67 fmol/ml), and thereafter kept fairly constant during the remaining neonatal period. Compared with term infants, mean TPO levels of preterm infants in CB and at d 2 were significantly higher (P < 0.01). There was an inverse correlation between platelet counts and TPO levels (r = 0.45, P < 0.001, n = 88). Preterm neonates with thrombocytosis had significantly higher TPO values in CB than those without thrombocytosis (P < 0.05). There was no significant relationship between platelet counts and IL-6. IL-11 was not detectable. These results suggest that an early elevation of serum TPO levels is related to the subsequent thrombocytosis in LBW preterm infants.
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Affiliation(s)
- K Matsubara
- Department of Paediatrics, Nishi-Kobe Medical Centre, 5-7-1 Kojidai, Nishi-ku, Kobe 651-2273, Japan.
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33
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Nako Y, Tachibana A, Fujiu T, Tomomasa T, Morikawa A. Neonatal thrombocytosis resulting from the maternal use of non-narcotic antischizophrenic drugs during pregnancy. Arch Dis Child Fetal Neonatal Ed 2001; 84:F198-200. [PMID: 11320049 PMCID: PMC1721247 DOI: 10.1136/fn.84.3.f198] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Neonatal thrombocytosis can result from maternal narcotic drug abuse. The case of a male infant is reported who was born to a woman with schizophrenia treated with non-narcotic psychotropic drugs during pregnancy; he developed severe prolonged thrombocytosis. The platelet count reached 1310 x 10(9)/l on day 15. This thrombocytosis persisted for three months. The patient was treated with dipyridamole. A bone marrow aspirate showed normal myeloid and erythroid precursors with an increased number of megakaryocytes. Plasma concentrations of interleukin 6 and thrombopoietin were suppressed. No obvious complications from the thrombocytosis occurred, and the platelet count fell to within the upper limit of normal after 3 months of age. This case indicates that thrombocytosis may occur in infants born to mothers treated with non-narcotic psychopharmaceutical drugs during pregnancy. The thrombocytosis in this case may have been induced by factors other than interleukin 6 or thrombopoietin.
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Affiliation(s)
- Y Nako
- Department of Paediatrics, Gunma University School of Medicine, Maebashi, Gunma, Japan.
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34
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Grisaru D, Deutsch V, Shapira M, Pick M, Sternfeld M, Melamed-Book N, Kaufer D, Galyam N, Gait MJ, Owen D, Lessing JB, Eldor A, Soreq H. ARP, A Peptide Derived from the Stress-Associated Acetylcholinesterase Variant, Has Hematopoietic Growth Promoting Activities. Mol Med 2001. [DOI: 10.1007/bf03401943] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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35
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Lin CH, Lo LJ, Wang ML, Chen YR, Noordhoff MS. Major Hematological Diseases Associated With Cleft Lip and Palate. Cleft Palate Craniofac J 2000. [DOI: 10.1597/1545-1569(2000)037<0512:mhdawc>2.0.co;2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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36
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Lin CH, Lo LJ, Wang ML, Chen YR, Noordhoff MS. Major hematological diseases associated with cleft lip and palate. Cleft Palate Craniofac J 2000; 37:512-5. [PMID: 11034036 DOI: 10.1597/1545-1569_2000_037_0512_mhdawc_2.0.co_2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE Cleft lip and palate is among the most common congenital anomalies. Its association with major blood disorders has rarely been reported. The purpose of this study was to report two patients who had major blood diseases associated with cleft lip and palate. PATIENTS AND RESULTS From June 1995 to December 1997, there were 2700 patients with cleft lip, cleft palate, or both who received treatment at Chang Gung Memorial Hospital. Two of them were found to have major hematological disorders. In both cases, the disorder was detected by preoperative blood cell counts and white cell differentiation. Case 1 was a 21-year-old woman patient with repaired right cleft lip. She was admitted for alveolar bone grafting and closure of oronasal fistula. Abnormal presentation of blast cells was found, and subsequent bone marrow study confirmed acute lymphocytic leukemia. Case 2 was a 26-year-old man with left secondary cleft lip nasal deformity scheduled to receive staged reconstructive operations. An elevated platelet count was found and subsequently confirmed to represent essential thrombocytosis. In both cases, reconstructive operations for the cleft-related deformities were performed. CONCLUSIONS Association of major hematological disorders and cleft lip, palate, or both is rare and is reported herein.
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Affiliation(s)
- C H Lin
- Chang Gung Memorial Hospital, Taipei, Taiwan
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37
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Wolber EM, Jelkmann W. Interleukin-6 increases thrombopoietin production in human hepatoma cells HepG2 and Hep3B. J Interferon Cytokine Res 2000; 20:499-506. [PMID: 10841078 DOI: 10.1089/10799900050023915] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
The concentration of circulating thrombopoietin (TPO) is relatively high in patients with thrombocytosis reactive to inflammatory diseases. We investigated whether immunomodulatory cytokines stimulate TPO synthesis in cultured human hepatoma cells (lines HepG2 and Hep3B), renal proximal tubular cells, and bone marrow fibroblasts. The effects of interleukins (IL) IL-1beta, IL-6, and IL-11 and of tumor necrosis factor-a (TNF-alpha) on the rate of TPO secretion were measured by ELISA. TPO mRNA levels were quantitated by competitive reverse transcription PCR. HepG2 and Hep3B cells produced significant amounts of TPO mRNA and TPO protein. Renal tubular cells synthesized less TPO, and in bone marrow fibroblasts, neither TPO mRNA nor TPO protein was detected. Only IL-6 affected TPO protein secretion, causing a 1.5-fold stimulation in HepG2 and Hep3B cells in 24-h incubation periods. The TPO mRNA content in these cells was doubled by IL-6 after 2, 6, or 24 h of stimulation. Thus, IL-6 could cause thrombocytosis in inflammatory disease partly by increasing hepatic TPO production.
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Affiliation(s)
- E M Wolber
- Institute of Physiology, Medical University of Luebeck, Germany
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38
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Abstract
Pulmonary hypertension (PH) is a chronic and disabling condition that affects the pulmonary vasculature. Once PH is diagnosed, the prognosis is generally poor with a rapid downhill course. PH management is largely empirical because the underlying pathophysiologic mechanisms that are responsible for the excessive vasoconstrictor and vascular smooth muscle proliferative responses are poorly understood. Based on new information concerning the role of adrenergic receptors in regulating various cellular functions, a new perspective on the genesis of PH has emerged, along with a unifying hypothesis for the role of alpha1-adrenergic receptors present in the pulmonary vasculature as the major contributor to the pathophysiologic changes associated with PH. Adrenergic receptors that are present on vascular smooth muscle cells regulate vascular tone and growth. The alpha1-adrenergic receptors that are present on the small- and medium-sized pulmonary arteries have a unique and greatly enhanced affinity and activity to alpha1-adrenergic agonists. Under physiologic conditions, this helps in regulating vascular tone and maintains an adequate ventilation/perfusion matching. However, the excessive stimulation of alpha1-adrenergic receptors produces not only smooth muscle contraction but also proliferation and growth. The conditions that produce an increase in alpha1-adrenoreceptor gene synthesis, density, and activity (such as hypoxia or changes in vessel wall pressure) or increase the levels of its agonists (such as norepinephrine, appetite suppressants, or cocaine) greatly enhance pulmonary vascular smooth muscle contractile and proliferative responses and lead to the development of PH. An understanding of the role played by these receptors in the pathophysiology of PH would not only help to avoid the use of alpha1-agonists for appetite suppression and other disease states, but also would help in developing new drugs to block these receptors. A further understanding of the alpha1-adrenoreceptor subtypes present in the pulmonary vasculature, the factors that regulate their expression, and their intracellular signaling pathways would help researchers to devise newer therapeutic strategies and, hopefully, to find a cure for this crippling condition.
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Affiliation(s)
- S S Salvi
- Department of Medicine, Southampton General Hospital, UK.
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39
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Salvi S, Blomberg A, Rudell B, Kelly F, Sandström T, Holgate ST, Frew A. Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers. Am J Respir Crit Care Med 1999; 159:702-9. [PMID: 10051240 DOI: 10.1164/ajrccm.159.3.9709083] [Citation(s) in RCA: 558] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Several epidemiologic studies have demonstrated a consistent association between levels of particulate matter (PM) in the ambient air with increases in cardiovascular and respiratory mortality and morbidity. Diesel exhaust (DE), in addition to generating other pollutants, is a major contributor to PM pollution in most places in the world. Although the epidemiologic evidence is strong, there are as yet no established biological mechanisms to explain the toxicity of PM in humans. To determine the impact of DE on human airways, we exposed 15 healthy human volunteers to air and diluted DE under controlled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy were performed 6 h after each exposure to obtain airway lavages and endobronchial biopsies. While standard lung function measures did not change following DE exposure, there was a significant increase in neutrophils and B lymphocytes in airway lavage, along with increases in histamine and fibronectin. The bronchial biopsies obtained 6 h after DE exposure showed a significant increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along with upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, with increases in the numbers of LFA-1+ cells in the bronchial tissue. Significant increases in neutrophils and platelets were observed in peripheral blood following DE exposure. This study demonstrates that at high ambient concentrations, acute short-term DE exposure produces a well-defined and marked systemic and pulmonary inflammatory response in healthy human volunteers, which is underestimated by standard lung function measurements.
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Affiliation(s)
- S Salvi
- University Medicine Department, Southampton General Hospital, Southampton, and Cardiovascular Research, The Rayne Institute, St Thomas Hospital, London, United Kingdom.
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40
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Griesshammer M, Bangerter M, Sauer T, Wennauer R, Bergmann L, Heimpel H. Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count. J Intern Med 1999; 245:295-300. [PMID: 10205592 DOI: 10.1046/j.1365-2796.1999.00452.x] [Citation(s) in RCA: 178] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
OBJECTIVE To determine the aetiology and clinical significance of an elevated platelet count (thrombocytosis) in a large cohort of patients. DESIGN A retrospective review of the medical records was performed on all patients, who had at least one platelet count > or = 500 x 10(9) L-1. SETTING Departments of Medicine and Surgery, University of Ulm, Germany. SUBJECTS A total of 732 patients with thrombocytosis. MAIN OUTCOME MEASURES Classification of thrombocytosis and thromboembolic complications, and evaluation of laboratory parameters distinguishing between primary and secondary thrombocytosis. RESULTS Of the total of 732 patients, 89 (12.3%) had primary and 643 (87.7%) had secondary thrombocytosis. Essential thrombocythaemia was observed in 40 of 89 patients (45%) with primary thrombocytosis. The most frequent causes of secondary thrombocytosis were tissue damage (42%), infection (24%), malignancy (13%) and chronic inflammation (10%). Primary thrombocytosis was significantly associated with a higher platelet count and an increased incidence of both arterial and venous thromboembolic complications. In secondary thrombocytosis, thromboembolic events were restricted to the venous system and occurred only in the presence of other risk factors. Mean values of leucocyte count, haematocrit, erythrocyte sedimentation rate, fibrinogen, serum potassium and lactate dehydrogenase were significantly different in primary and secondary thrombocytosis. CONCLUSIONS The finding of an elevated platelet count on routine blood examination has diagnostic, prognostic and therapeutic implications. It is of clinical importance to distinguish between primary and secondary thrombocytosis, as thrombotic complications occur more frequently in primary thrombocytosis. Unless additional risk factors are present, secondary thrombocytosis is not associated with a significant risk for thromboembolic events.
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41
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Bardo DM, Applegate KE, Goske MJ, Kuivila TE, Goldfarb J. Superficial venous thrombosis presenting as a painful popliteal fossa mass in a child. JOURNAL OF CLINICAL ULTRASOUND : JCU 1998; 26:470-473. [PMID: 9800162 DOI: 10.1002/(sici)1097-0096(199811/12)26:9<470::aid-jcu7>3.0.co;2-k] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
We report an unusual case of superficial venous thrombosis in a cyanotic 12-year-old child who had undergone recent appendectomy. Although compression, color Doppler, and duplex ultrasound techniques remain the keys to the diagnosis of venous thrombosis, SieScape sonography was beneficial in demonstrating the extent of the thrombi and their location along a superficial thrombosed vein.
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Affiliation(s)
- D M Bardo
- Department of Radiology Hb6, Cleveland Clinic Foundation, OH 44195, USA
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