RESUMO
BACKGROUND: Primary immune thrombocytopenia is an autoimmune disorder mediated partly by platelet autoantibodies, resulting in thrombocytopenia, bleeding, and constitutional symptoms. Efgartigimod, a first-in-class novel human IgG1 Fc fragment, binds the neonatal Fc receptor with high affinity and thus reduces serum IgG concentrations, including autoantibodies. The objective of this study was to evaluate the efficacy and safety of efgartigimod in adults with persistent and chronic primary immune thrombocytopenia. METHODS: This phase 3, multicentre, randomised, double-blinded, placebo-controlled, 24-week study evaluated the efficacy and safety of intravenous efgartigimod in adults aged 18 years or older with chronic or persistent primary immune thrombocytopenia who had an average platelet count of less than 30 000, had responded to at least one previous immune thrombocytopenia therapy, and were on a concurrent therapy at baseline or had received at least a second previous immune thrombocytopenia therapy. The study took place in 71 participating sites from Asia, Europe, and North America. Patients were randomly assigned 2:1 to receive either efgartigimod (10 mg/kg) or placebo intravenously for the first 4 weeks, after which the dosing schedule could be altered to once per week or every other week depending on the patients' platelet count. The primary endpoint, evaluated in the chronic population, was sustained platelet count response (≥50 × 109 for at least 4 of the last 6 weeks). This study is registered with ClinicalTrials.gov (NCT04188379) and is completed. FINDINGS: A total of 205 patients were screened from Dec 9, 2019, to Feb 3, 2022, and 131 (86 in the efgartigimod group; 45 in the placebo group) were randomly assigned. These patients represented a population with long-term disease who had a mean time since diagnosis of 10·6 years and 67% (88/131) of whom had received at least three previous immune thrombocytopenia treatments. 22% (17/78) of patients with chronic immune thrombocytopenia receiving efgartigimod reached the primary endpoint compared with 5% (2/40) of those receiving placebo (p=0·032; adjusted difference in response, 16% [95% CI 2·6-26·4]). The median number of weeks of disease control in patients with chronic immune thrombocytopenia was 2·0 (IQR 0·0-11·0) for efgartigimod versus 0·0 (0·0-1·0) for placebo (p=0·0009). Efgartigimod was well tolerated; most adverse events were mild to moderate in severity. The most common adverse events of interest in both groups were headache (16% in efgartigimod and 13% in placebo), haematuria (16% in efgartigimod and 16% in placebo), and petechiae (15% in efgartigimod and 27% in placebo). INTERPRETATION: Efgartigimod significantly increased sustained platelet count responses compared with placebo in patients with chronic immune thrombocytopenia, including those who had received multiple previous immune thrombocytopenia therapies. Upon completion of the ADVANCE IV study, patients could enroll in the ongoing open-label extension. Subcutaneous efgartigimod is currently being evaluated in patients with immune thrombocytopenia in the ADVANCE SC+ trial. FUNDING: argenx.
Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adulto , Humanos , Autoanticorpos , Método Duplo-Cego , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Resultado do TratamentoRESUMO
Cases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 117 patients with preexisting ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count <30 × 109/L with >20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK patients with ITP, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in preexisting ITP or be identified de novo post-SARS-CoV2 vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those postsplenectomy and with more refractory disease, is indicated.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Púrpura Trombocitopênica Idiopática , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , Plaquetas/imunologia , Plaquetas/metabolismo , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/imunologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Esplenectomia , Reino Unido/epidemiologiaRESUMO
Primary immune thrombocytopenia (ITP) is an acquired blood disorder that causes a reduction in circulating platelets with the potential for bleeding. The incidence of ITP is slightly higher in adults and affects more women than men until 60 years, when males are more affected. Despite advances in basic science, primary ITP remains a diagnosis of exclusion. The disease is heterogeneous in its clinical behavior and response to treatment. This reflects the complex underlying pathophysiology, which remains ill-understood. Platelet destruction plays a role in thrombocytopenia, but underproduction is also a major contributing factor. Active ITP is a proinflammatory autoimmune disease involving abnormalities within the T and B regulatory cell compartments, along with several other immunological abnormalities. Over the last several years, there has been a shift from using immunosuppressive therapies for ITP towards approved treatments, such as thrombopoietin receptor agonists. The recent COVID-19 pandemic has hastened this management shift, with thrombopoietin receptor agonists becoming the predominant second-line treatment. A greater understanding of the underlying mechanisms has led to the development of several targeted therapies, some of which have been approved, with others still undergoing clinical development. Here we outline our view of the disease, including our opinion about the major diagnostic and therapeutic challenges. We also discuss our management of adult ITP and our placement of the various available therapies.
Assuntos
COVID-19 , Púrpura Trombocitopênica Idiopática , Adulto , Feminino , Humanos , Púrpura Trombocitopênica Idiopática/terapia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores de Trombopoetina/agonistas , Receptores de Trombopoetina/uso terapêutico , Pandemias , Plaquetas , Teste para COVID-19RESUMO
BACKGROUND: Adult primary immune thrombocytopenia (ITP) is a rare bleeding disorder of unknown cause. Recent estimates of its incidence and trend over time were acquired for England. METHOD: The primary ITP population (using ICD 10 code D693 and excluding secondary ITP cases; positive predictive value: 82.6%) was sourced from NHS Digital inpatient and outpatient. Incidence rate (IR) for England and by age groups, sex, and regions were calculated and trends were assessed using average annual percent change (AAPC). RESULTS: A total of 25 805 patients (mean age 59 years; females 57.8%) diagnosed between 2003 and 2014 was identified. IRs increased from 4.2/100 000 to 6.4/100 000 over this period (AAPC:4.3%). For all sex-specific age groups, the IRs significantly increased over time, except 18-29 years males. The greatest increase was among females aged 30-39 (AAPC:8.7%). In contrast, among ≥70 years, ITP was more common in males (highest IR among ≥80 years males: 23.9/100 000). England's average annual IR was 6.1/100 000 for 2010-14. An estimated 2.5/100 000 (based on UKITP Registry data) was estimated to require 1st line treatment whereas 2.4/100 000 would have 1st and 2nd line treatments within 6 months from diagnosis. IRs for London and East Midlands were the highest (6.5/100 000). CONCLUSIONS: This study found a rising incidence of primary ITP, with sharp increases among young women and elderly men. These findings put in context the impact of ITP on patients' lives and the healthcare services in England, especially with 17%-50% who may develop chronic ITP and require long-term care.
Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adulto , Idoso , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/terapia , Sistema de RegistrosRESUMO
Immune thrombocytopenia (ITP) is an autoimmune disorder in which a combination of defective platelet production and enhanced clearance leads to thrombocytopenia. The primary aim for therapy in patients with this condition is the prevention of bleeding. However, more recently, increased rates of venous and arterial thrombotic events have been reported in ITP, even in the context of marked thrombocytopenia. In this review we discuss the epidemiology, aetiology and management of thrombotic events in these patients. We consider the impact of ITP therapies on the increased thrombotic risk, in particular the use of thrombopoietin-receptor agonists (TPO-RAs), as well as factors inherent to ITP itself. We also discuss the limited evidence available to guide clinicians in the treatment of these complex cases.
Assuntos
Púrpura Trombocitopênica Idiopática/complicações , Trombose/etiologia , Animais , Gerenciamento Clínico , Hemorragia/prevenção & controle , Humanos , Púrpura Trombocitopênica Idiopática/terapia , Receptores de Trombopoetina/agonistas , Fatores de Risco , Trombose/induzido quimicamente , Trombose/terapiaRESUMO
This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID-19 pandemic. The intention is to support clinicians and, although recommendations have been provided, it is not a formal guideline. Nor is there sufficient evidence base to conclude that alternative approaches to treatment are incorrect. Instead, it is a consensus written by clinicians with an interest in ITP or coagulation disorders and reviewed by members of the UK ITP forum.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Púrpura Trombocitopênica Idiopática , Adulto , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto , Púrpura Trombocitopênica Idiopática/congênito , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/terapia , SARS-CoV-2RESUMO
Romiplostim self-administration by patients or caregivers may offer time/cost savings to healthcare professionals (HCPs) and convenience for patients who avoid weekly clinic visits. We performed an integrated analysis of five clinical trials to evaluate the efficacy and safety of romiplostim self-administration. Data were analyzed from adults with immune thrombocytopenia (ITP) who received weekly romiplostim via self-administration or from an HCP. Patients who achieved a stable romiplostim dose for ≥3 weeks (HCP group ≥5 weeks to provide an appropriate index date to enable comparisons with the self-administration group) with platelet counts ≥50 × 109 /L were eligible. In the self-administration (n = 621) vs HCP (n = 133) groups, respectively, median age was 53 vs 58 years, median time since primary ITP diagnosis was 3.7 vs 2.5 years, and median baseline platelet count at ITP diagnosis was 19.0 vs 20.0 × 109 /L. In the self-administration and HCP-dosed groups, median romiplostim treatment duration was 89 vs 52 weeks and median total number of doses was 81 vs 50, respectively. In the self-administration and HCP groups, respectively: 95.0% and 100.0% of patients achieved ≥1 platelet response (defined as weekly platelet count ≥50 × 109 /L without rescue medication in previous 4 weeks); the median percentage of weeks with a response was 94.5% and 95.9%; and rescue medication was used in 36.7% and 39.8% of patients. Self-administration did not adversely affect safety; duration-adjusted rates for all treatment-emergent adverse events (TEAEs) and bleeding TEAEs were numerically lower with self-administration. Romiplostim self-administration appears effective and well tolerated in eligible patients with ITP.
Assuntos
Bases de Dados Factuais , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Trombopoetina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Proteínas Recombinantes de Fusão/efeitos adversos , Autoadministração , Trombopoetina/efeitos adversosRESUMO
Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, characterized by a low platelet count (<100 × 109 /L) in the absence of other causes associated with thrombocytopenia. In most patients, IgG autoantibodies directed against platelet receptors can be detected. They accelerate platelet clearance and destruction, inhibit platelet production, and impair platelet function, resulting in increased risk of bleeding and impaired quality of life. Efgartigimod is a human IgG1 antibody Fc-fragment, a natural ligand of the neonatal Fc receptor (FcRn), engineered for increased affinity to FcRn, while preserving its characteristic pH-dependent binding. Efgartigimod blocks FcRn, preventing IgG recycling, and causing targeted IgG degradation. In this Phase 2 study, 38 patients were randomized 1:1:1 to receive four weekly intravenous infusions of either placebo (N = 12) or efgartigimod at a dose of 5 mg/kg (N = 13) or 10 mg/kg (N = 13). This short treatment cycle of efgartigimod in patients with ITP, predominantly refractory to previous lines of therapy, was shown to be well tolerated, and demonstrated a favorable safety profile consistent with Phase 1 data. Efgartigimod induced a rapid reduction of total IgG levels (up to 63.7% mean change from baseline), which was associated with clinically relevant increases in platelet counts (46% patients on efgartigimod vs 25% on placebo achieved a platelet count of ≥50 × 109 /L on at least two occasions, and 38% vs 0% achieved ≥50 × 109 /L for at least 10 cumulative days), and a reduced proportion of patients with bleeding. Taken together, these data warrant further evaluation of FcRn antagonism as a novel therapeutic approach in ITP.
Assuntos
Fragmentos Fc das Imunoglobulinas/uso terapêutico , Imunoglobulina G/uso terapêutico , Púrpura Trombocitopênica Idiopática , Receptores Fc/antagonistas & inibidores , Adulto , Idoso , Método Duplo-Cego , Feminino , Seguimentos , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/sangueRESUMO
The thrombopoietin receptor agonist romiplostim is approved for second-line use in chronic immune thrombocytopenia (ITP), but its effects in patients with ITP for ≤1 year are not well characterized. This analysis of pooled data from 9 studies included patients with ITP for ≤1 year (n = 311) or >1 year (n = 726) who failed first-line treatments and received romiplostim, placebo or standard of care. In subgroup analysis by ITP duration, patient incidences for platelet response at ≥75% of measurements were higher for romiplostim [ITP ≤1 year: 74% (204/277); ITP >1 year: 71% (450/634)] than for placebo/standard of care [ITP ≤1 year: 18% (6/34); ITP >1 year: 9% (8/92)]. Of patients with ≥9 months on study, 16% with ITP ≤1 year and 6% with ITP >1 year discontinued romiplostim and maintained platelet counts ≥50 × 109 /l for ≥6 months without ITP treatment (treatment-free remission). Independent of ITP duration, rates of serious adverse events and bleeding were lower with romiplostim than placebo/standard of care and thrombotic events occurred at similar rates. In this analysis, romiplostim and placebo/standard of care had similar safety profiles and romiplostim increased platelet counts in patients with either ITP ≤1 year or ITP >1 year, with more treatment-free remission in those with ITP ≤1 year.
Assuntos
Púrpura Trombocitopênica Idiopática , Receptores Fc , Proteínas Recombinantes de Fusão , Trombopoetina , Adulto , Idoso , Doença Crônica , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Trombopoetina/administração & dosagem , Trombopoetina/efeitos adversos , Trombose/sangue , Trombose/induzido quimicamente , Trombose/diagnóstico , Fatores de TempoRESUMO
BACKGROUND: Romiplostim is a thrombopoietin-mimetic peptibody for adult refractory chronic immune thrombocytopenia (ITP). We aimed to describe ITP patients receiving romiplostim, platelet counts and romiplostim usage in UK clinical practice. METHODS: This was a retrospective cohort study of patients in the UKITP Registry who received romiplostim between October 2009 and January 2015, including data up to 6 months before romiplostim initiation through follow-up. RESULTS: Of 1440 patients in the UKITP Registry, 118 adults with primary ITP were eligible. Before romiplostim, 22% had splenectomy, 12% received platelet transfusion, 97% received ≥ 1 different ITP medication and 77% received ≥ 3. Most patients (73%) initiated romiplostim ≥ 1 year after ITP diagnosis (chronic phase). The mean duration of romiplostim treatment was 5.7 (SE 0.9) months, and the median was 1.4 months (IQR: 0.2, 6.5). Mean platelet count before romiplostim was 38 × 109 /L, rising to 103 × 109 /L within 1 month, and remaining 50-150 × 109 /L through up to 3 years of follow-up. After romiplostim, 4% of patients had splenectomy, 6% received platelet transfusion, and 57% received just one ITP medication other than romiplostim. CONCLUSION: The study provides valuable insights into the real-world use of romiplostim in primary ITP in routine practice and highlighted the timing of romiplostim initiation at different ITP disease phases.
Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Coagulação Sanguínea , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Padrões de Prática Médica , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento , Reino Unido , Adulto JovemRESUMO
In anecdotal reports, some patients with immune thrombocytopenia (ITP) maintained platelet counts after discontinuing romiplostim. Here, we examined rates of platelet response (≥50 × 10(9) /l), remission, splenectomy and adverse events in patients with primary ITP duration ≤6 months who were treated with romiplostim for ≤12 months. The starting dose of romiplostim was 1 µg/kg; concomitant and rescue treatments were permitted to maintain platelet counts. Patients with platelet counts ≥50 × 10(9) /l at the end of 12 months entered a dose taper in which the romiplostim dose was decreased as long as platelet counts were maintained. Remission (platelet count ≥50 × 10(9) /l for 24 consecutive weeks with no ITP treatments) was evaluated in patients once romiplostim was discontinued. Over the 12 months, a high response rate (>90%) was observed. Platelet response occurred quickly (median, ~2 weeks) and was observed for a cumulative median of 11 months. Remission was observed in 24 patients (32%); there were no significantly predictors of remission. Most (20/24) patients had remission start before the forced taper. No new safety signals were identified. Thus, in patients with early-stage ITP, romiplostim was well tolerated and induced rapid responses, with remission occurring in approximately one-third of patients (NCT01143038, Amgen 20080435).
Assuntos
Doenças Autoimunes/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombocitopenia/tratamento farmacológico , Trombopoetina/uso terapêutico , Adulto , Doenças Autoimunes/sangue , Plaquetas/efeitos dos fármacos , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Receptores Fc/administração & dosagem , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Indução de Remissão , Trombocitopenia/sangue , Trombopoetina/administração & dosagem , Trombopoetina/efeitos adversos , Resultado do TratamentoRESUMO
Primary immune thrombocytopenia is an autoimmune disorder in which platelet destruction is a consequence of both B- and T-cell dysregulation. Flow cytometry was used to further characterize the B- and T-cell compartments in a cross-sectional cohort of 26 immune thrombocytopenia patients including antiplatelet antibody positive (n=14) and negative (n=12) patients exposed to a range of therapies, and a cohort of matched healthy volunteers. Markers for B-cell activating factor and its receptors, relevant B-cell activation markers (CD95 and CD21) and markers for CD4(+) T-cell subsets, including circulating T-follicular helper-like cells, were included. Our results indicate that an expanded population of CD95(+) naïve B cells correlated with disease activity in immune thrombocytopenia patients regardless of treatment status. A population of CD21-naïve B cells was specifically expanded in autoantibody-positive immune thrombocytopenia patients. Furthermore, the B-cell maturation antigen, a receptor for B-cell activating factor, was consistently and strongly up-regulated on plasmablasts from immune thrombocytopenia patients. These observations have parallels in other autoantibody-mediated diseases and suggest that loss of peripheral tolerance in naïve B cells may be an important component of immune thrombocytopenia pathogenesis. Moreover, the B-cell maturation antigen represents a potential target for plasma cell directed therapies in immune thrombocytopenia.
Assuntos
Linfócitos B/imunologia , Linfócitos B/metabolismo , Fenótipo , Plasmócitos/imunologia , Plasmócitos/metabolismo , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/metabolismo , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , Fator Ativador de Células B/sangue , Fator Ativador de Células B/metabolismo , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/patologia , Biomarcadores , Plaquetas/imunologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Plasmócitos/patologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto JovemRESUMO
Adults with primary immune thrombocytopenia (ITP) may be susceptible to thromboembolism (TE). The objective of this systematic review was to evaluate studies that reported the prevalence and risk of developing TE in the ITP population from ITP diagnosis and splenectomy. We searched several bibliographic databases and included 29 studies. Using meta-analytical techniques, the pooled prevalence of TE before ITP diagnosis was 7.84% (arterial 6.25%; venous 1.95%). The pooled 'annualised' cumulative incidence (without prior TE) and cumulative risk (irrespective of prior TE) were 1.29%/yr and 3.00%/yr, respectively. Splenectomised patients had pooled cumulative risk of arterial TE (ATE) and venous TE (VTE) of 0.19%/yr and 1.10%/yr, respectively. In cohorts, regardless of a history of TE, the pooled relative risk (RR) of any TE was 1.60 (1.34, 1.86) for ITP vs. ITP-free individuals [arterial: 1.52 (1.25, 1.80); venous: 1.70 (0.96, 2.43)]. Splenectomised patients were at higher risk of venous events, pooled RR 2.39 (1.61, 3.17). To conclude, we found an increased risk of TE (mainly ATE) among ITP individuals and a higher risk of VTEs after splenectomy. How intrinsic (ITP pathophysiology, age, gender) and extrinsic factors (treatment) contribute to this risk could not be investigated here but is a task for future studies.
Assuntos
Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/epidemiologia , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Adulto , Fatores Etários , Humanos , Incidência , Prevalência , RiscoRESUMO
Fatigue is an important aspect of health-related quality of life from the patient perspective and can have significant socio-economic consequences. It is a common feature of chronic illnesses and a significant number of both adults and children with immune thrombocytopenia (ITP) suffer from fatigue. Reliable, validated fatigue scales have been developed for use in ITP. These will facilitate future investigation of its pathogenesis and the effectiveness of intervention. Acute inflammation acts on neural and endocrine systems resulting in 'sickness behaviour', an adaptive response to infection and injury. Inflammation is also thought to cause fatigue in chronic disease and immune dysregulation in ITP appears to have a number of pro-inflammatory components. Clinicians should consider fatigue when assessing the burden of disease. Although effective ITP-directed therapy can improve fatigue, a number of fatigue-directed strategies may also need to be considered.
Assuntos
Fadiga/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Fadiga/diagnóstico , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/terapia , Qualidade de VidaRESUMO
Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with thrombopoietin receptor agonists (TPO-RA). However, fibrosis has also been reported in patients with various stages of ITP, who were TPO-RA treatment-naïve. In our study, we looked for fibrosis in bone marrow trephine biopsies taken at initial diagnosis from 32 adult patients with ITP. Ten of the 32 evaluated samples (31·25%) showed increased reticulin (Grade 1-2 on Bauermeister scale and Grade 0-1 on the European Consensus scale), which showed a positive correlation with ethnicity (0·3%) but did not correlate with disease severity, any clinical features or co-morbidities.
Assuntos
Mielofibrose Primária/patologia , Púrpura Trombocitopênica Idiopática/patologia , Sistema de Registros , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/complicações , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/epidemiologia , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/epidemiologia , Receptores de Trombopoetina/agonistas , Estudos Retrospectivos , Índice de Gravidade de Doença , Reino UnidoRESUMO
In a previous publication on new terminology, definitions, and outcome criteria for immune thrombocytopenia (ITP), the International Working Group (IWG) on ITP acknowledged that response to treatment should consist of clinically meaningful end points such as bleeding manifestations and that platelet count may not be the ideal parameter for capturing the benefits of therapy. The IWG now proposes a consensus-based ITP-specific bleeding assessment tool (ITP-BAT) with definitions and terminology consistent with those adopted for other bleeding disorders. Bleeding manifestations were grouped into three major domains: skin (S), visible mucosae (M), and organs (O), with gradation of severity (SMOG). Each bleeding manifestation is assessed at the time of examination. Severity is graded from 0 to 3 or 4, with grade 5 for any fatal bleeding. Bleeding reported by the patient without medical documentation is graded 1. Within each domain, the same grade is assigned to bleeding manifestations of similar clinical impact. The "worst bleeding manifestation since the last visit" (observation period) is graded (a suitable database collection form is provided), and the highest grade within each domain is recorded. The SMOG system provides a consistent description of the bleeding phenotype in ITP, and the IWG unanimously supports its adoption and validation in future clinical studies.
Assuntos
Hematologia/normas , Hemorragia/sangue , Hemorragia/diagnóstico , Guias de Prática Clínica como Assunto , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Humanos , Padrões de Referência , Índice de Gravidade de Doença , Terminologia como AssuntoRESUMO
Immune thrombocytopenia (ITP) is an autoimmune bleeding disease caused by immune-mediated platelet destruction and decreased platelet production. ITP is characterized by an isolated thrombocytopenia (<100 × 109/L) and increased risk of bleeding. The disease has a complex pathophysiology wherein immune tolerance breakdown leads to platelet and megakaryocyte destruction. Therapeutics such as corticosteroids, intravenous immunoglobulins (IVIg), rituximab, and thrombopoietin receptor agonists (TPO-RAs) aim to increase platelet counts to prevent hemorrhage and increase quality of life. TPO-RAs act via stimulation of TPO receptors on megakaryocytes to directly stimulate platelet production. Romiplostim is a TPO-RA that has become a mainstay in the treatment of ITP. Treatment significantly increases megakaryocyte maturation and growth leading to improved platelet production and it has recently been shown to have additional immunomodulatory effects in treated patients. This review will highlight the complex pathophysiology of ITP and discuss the usage of Romiplostim in ITP and its ability to potentially immunomodulate autoimmunity.
Assuntos
Púrpura Trombocitopênica Idiopática , Receptores Fc , Proteínas Recombinantes de Fusão , Trombopoetina , Humanos , Receptores Fc/uso terapêutico , Trombopoetina/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores de Trombopoetina/agonistasRESUMO
Romiplostim was effective, safe, and well-tolerated over 6-12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP). This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin/fibrosis), platelet response (platelet count >50 × 10(9) per litre), and the proportion of patients requiring rescue treatments. Treatment-related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5% of patients and were not associated with platelet count. Median platelet counts of 50-200 × 10(9) per litre were maintained with stable doses of romiplostim (mean 5-8 µg/kg; generally self-administered at home) throughout the study. A platelet response was achieved at least once by 95% of patients, with a platelet response maintained by all patients on a median 92% of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and well-tolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.
Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Adulto , Idoso , Doenças da Medula Óssea/induzido quimicamente , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Hemorragia/etiologia , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/cirurgia , Proteínas Recombinantes de Fusão/efeitos adversos , Autoadministração , Esplenectomia , Trombocitopenia/induzido quimicamente , Trombopoetina/efeitos adversos , Trombose/induzido quimicamenteAssuntos
Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Gerenciamento Clínico , Pesquisas sobre Atenção à Saúde , Humanos , Padrões de Prática Médica , Receptores de Trombopoetina/agonistas , Receptores de Trombopoetina/antagonistas & inibidores , Reino UnidoRESUMO
CD160 is a human natural killer (NK)-cell-activating receptor that is also expressed on T-cell subsets. In the present study, we examined 811 consecutive cases of B-cell lymphoproliferative disorders (B-LPDs), and demonstrated CD160 expression in 98% (590 of 600) of chronic lymphocytic leukemia (CLL) cases, 100% (32 of 32) of hairy cell leukemia (HCL) cases, 15% (5 of 34) of mantle cell lymphoma (MCL) in the leukemic phase, and 16% (23 of 145) of other B-LPD cases. CD160 transcript and protein were absent in the normal B-cell hierarchy, from stem cells, B-cell precursors, maturing B cells in the germinal center, and circulating B cells, including CD5(+)CD19(+) B1 cells in umbilical cord. CD160 positivity was significantly higher in CLL and HCL in terms of percentage (65.9% and 67.8%, respectively, P < .0001) and median fluorescence intensity (552 and 857, respectively, P < .0001) compared with all other B-LPD cases. Lymph node CLL samples were also CD160(+). Using the disease-specific expression of CD5, CD23, and CD160, a score of 3 characterized CLL (diagnostic odds ratio, 1430); a score of 0 excluded CLL, MCL, and HCL; and the CD23/CD5 ratio differentiated CLL from leukemic CD23(+) MCL. In the B-cell lineage, CD160 is a tumor-specific antigen known to mediate cellular activation signals in CLL, and is a novel target for therapeutic manipulation and monitoring of minimal residual disease.