[Guideline for diagnosis and treatment of immune thrombocytopenia]. / Trombocitopenia inmune. Guía de diagnóstico y tratamiento.

Management, outcome, diagnosis, prognosis and treatment of immune thrombocytopenia are controversial. Several guidelines stating different experts' opinions have been published; however, no worldwide consensus regarding the management of the disease has still been reached. This guideline defines diagnostic criteria, states initial laboratory tests, establishes differential diagnosis, develops topics concerning outcome and prognosis, and enumerates available treatments for acute and chronic disease, as well as for management of life-threatening bleeding.

El manejo de la trombocitopenia inmune es motivo de discusión en lo concerniente a evolución, diagnóstico, pronóstico y tratamiento. Se han publicado varias guías que expresan distintas opiniones de expertos, pero no existe aún consenso mundial sobre cuál es el manejo más adecuado de la enfermedad. Esta guía establece los criterios para definir el diagnóstico; detalla el plan de estudios de laboratorio por realizar inicialmente; plantea los distintos diagnósticos diferenciales; desarrolla aspectos relativos a evolución y pronóstico, y enumera los tratamientos disponibles para las formas agudas y las crónicas, así como para el manejo de las emergencias y en algunas situaciones especiales.

Circulating myeloid-derived suppressor cells predict disease activity and treatment response in patients with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is a disease characterized by isolated thrombocytopenia. Abnormal effector T cell activation is an important mechanism in the pathogenesis of ITP. Regulatory T cells (Treg) have a strong immunosuppressive function for T cell activation and their importance in the pathophysiology and clinical treatment of ITP has been confirmed. Myeloid-derived suppressor cells (MDSCs) are other immunosuppressive cells, which can also suppress T cell activation by secreting arginase, iNOS and ROS, and are essential for Treg cells' differentiation and maturation. Therefore, we speculate that MDSCs might also be involved in the immune-dysregulation mechanism of ITP. In this study, we tested MDSCs and Treg cells in peripheral blood samples of twenty-five ITP patients and ten healthy donors. We found that MDSCs and Treg cells decreased simultaneously in active ITP patients. Relapsed ITP patients showed lower MDSCs levels compared with new patients. All patients received immunosuppressive treatment including dexamethasone alone or in combination with intravenous immune globulin. We found that MDSCs' level after treatment correlated with platelet recovery. Our study is the first that focused on MDSCs' role in ITP. Based on our results, we concluded that circulating MDSCs could predict disease activity and treatment response in ITP patients. This preliminary conclusion indicates a substantial significance of MDSCs in the pathophysiology and clinical treatment of ITP, which deserves further investigation.

Circulating myeloid-derived suppressor cells predict disease activity and treatment response in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is a disease characterized by isolated thrombocytopenia. Abnormal effector T cell activation is an important mechanism in the pathogenesis of ITP. Regulatory T cells (Treg) have a strong immunosuppressive function for T cell activation and their importance in the pathophysiology and clinical treatment of ITP has been confirmed. Myeloid-derived suppressor cells (MDSCs) are other immunosuppressive cells, which can also suppress T cell activation by secreting arginase, iNOS and ROS, and are essential for Treg cells’ differentiation and maturation. Therefore, we speculate that MDSCs might also be involved in the immune-dysregulation mechanism of ITP. In this study, we tested MDSCs and Treg cells in peripheral blood samples of twenty-five ITP patients and ten healthy donors. We found that MDSCs and Treg cells decreased simultaneously in active ITP patients. Relapsed ITP patients showed lower MDSCs levels compared with new patients. All patients received immunosuppressive treatment including dexamethasone alone or in combination with intravenous immune globulin. We found that MDSCs’ level after treatment correlated with platelet recovery. Our study is the first that focused on MDSCs’ role in ITP. Based on our results, we concluded that circulating MDSCs could predict disease activity and treatment response in ITP patients. This preliminary conclusion indicates a substantial significance of MDSCs in the pathophysiology and clinical treatment of ITP, which deserves further investigation.

Does Helicobacter pylori eradication play a role in immune thrombocytopenia? / ¿Tiene algún rol la erradicación de Helicobacter pylori en la trombocitopenia inmune?

Helicobacter pylori infection has been implicated as trigger or disease modifier in immune thrombocytopenia (ITP). So, eradication treatment for this agent could have clinical benefits. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews comprising 40 studies addressing the question of this article overall, including one randomized controlled trial. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded Helicobacter eradication might decrease risk of bleeding in patients with immune thrombocytopenia but the certainty of the evidence is low.

Se ha planteado que el Helicobacter pylori tendría un rol etiopatogénico en la trombocitopenia inmune (PTI), y que la erradicación de este podría tener beneficios clínicos. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos cuatro revisiones sistemáticas que en conjunto incluyen 40 estudios, entre ellos un estudio controlado aleatorizado, que responden la pregunta de interés. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la erradicación de Helicobacter podría disminuir el riesgo de sangrado en pacientes con trombocitopenia inmune, pero la certeza de la evidencia es baja.

A Case of Fenofibrate-Induced Immune Thrombocytopenia: First Report.

Fenofibrate is widely prescribed as a hypolipidemic drug and is well tolerated by most patients. We present the case of a 40-year-old woman who developed severe immune thrombocytopenia while on fenofibrate treatment. Clinical features included spontaneous bruising on the feet and hands, a purpuric rash, and menorrhagia. All the laboratory results were normal except for the finding of isolated thrombocytopenia. The subsequent evolution was favorable after fenofibrate removal and with the administration of immunoglobulin G (IgG) plus corticosteroids. Drug-induced thrombocytopenia is briefly reviewed, and a possible mechanism responsible for causing this side effect of fenofibrate is suggested. This is the first reported case of fenofibrate-induced immune thrombocytopenia.

[Treatment of chronic immune thrombocytopenic purpura. Looking for something better. Review]. / Tratamiento de la púrpura trombocitopénica inmune crónica. Buscando algo mejor. Revisión.

Chronic Immune Thrombocytopenic Purpura (cITP) has become a field of multiple therapeutic assays. More than 20 types of treatment have been developed to obtain a favorable and prolonged platelet response. The treatment of cITP is oriented to inhibit the antiplatelet antibodies production by interference with the macrophage of the reticulum endothelial system and a blockade of the antigenic response with a decrease in the amplification of the immunological response. Steroids of the glucocorticoids type and splenectomy constitute the first line of treatment. Failure of these treatments leads to the use of second line drugs such as non steroid immuno-supressors and the immunoglobulins type IgG and anti-D. Therapeutic assays with others immunomodulators have been reported. The introduction of new drugs destined to increase the megakaryocytic bone marrow platelet production, has opened a new way to treat the cITP. However, the splenectomy remains as the simplest, safest and most effective treatment in cITP. The principal criteria does not have to be focused on obtaining a normal platelet count, but to reach safe hemostatic levels in absence of hemorrhage, for a prolonged time. On the other hand, despite the persistence of thrombocytopenia, the hematologist can choose to maintain the patient with no treatment and with only a strict clinical observation. It is obvious that the cost-benefit from the different treatments is inclined towards those of lower cost and minimal secondary effects.

Predisposition to idiopathic thrombocytopenic purpura maps close to the major histocompatibility complex class I chain-related gene A.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune condition with poorly known etiology, characterized by platelet destruction. Genetic association studies of this disease are scarce, discrepant, and restricted to major histocompatibility complex (MHC) polymorphisms. Hence, a case-control study was conducted with an aim to map the MHC to IPT susceptibility using HLA-B and nine microsatellite loci encompassing MHC class I, II, and III regions. We compared the allelic frequencies in samples of unrelated healthy controls and ITP patients. After correction for multiple tests, only allele MICA*183, also known as A5.1, demonstrated an association, resulting in the identification of a major predisposing region close to STR-MICA. This result may highlight the putative functional role of MICA in the immune response to ITP.

Demographic data, natural history, and prognostic factors of idiopathic thrombocytopenic purpura in children: a multicentered study from Argentina.

BACKGROUND: Demographics, outcome, and management of idiopathic thrombocytopenic purpura (ITP) in children present differences between countries. Although several factors influence outcome, it is impossible to predict at diagnosis which patients will have acute or chronic disease. High rates of spontaneous remission in chronic ITP have been reported. PROCEDURE: Data concerning 1,683 patients with ITP diagnosed from 1981 to date are presented; outcome was evaluated in 1,418 children. RESULTS: Remarkable presenting features were an incidence peak in the first 2 years of age and male predominance in patients <24 months of age. Three age groups with different recovery rates (P < 0.001) were established (2-12 months: 89.8%; 1-8 years: 71.3%; 9-18 years: 49.0%). Platelet count <10 x 10(9)/L and history of previous illness were associated with higher remission rates only in patients >12 months of age. The score developed by the NOPHO Group showed a predictive value of 83.9% for acute ITP. Spontaneous remission between 6 months and 11 years from diagnosis was achieved by 107 of 325 (32.9%) non-splenectomized children with chronic ITP, and in 44.9% of them between 6 and 12 months from diagnosis. CONCLUSIONS: Age and score were main prognostic factors. Infants <1 year of age are a special group with a brief course and very high recovery rate that are not influenced by other prognostic factors. Definition of groups based on age and scoring could be useful to establish differential management guidelines. The cut-off value to define chronic ITP should be changed to 12 months.

Púrpura trombocitopênica imune: diagnóstico e tratamento / Immune thrombocytopenic purpura: diagnosis and treatment

Objetivo: revisar os critérios vigentes para o diagnóstico e o tratamento da púrpura trombocitopênica imune da criança. Fonte dos dados: foram selecionados os artigos da literatura da base MedLine mais relevantes dos últimos 20 anos relativos ao termo púrpura trombocitopênica...

Objective: to assess the current criteria for immune thrombocytopenic purpura (PTI) diagnosis and tretament. Data source: MedLine database articles published in the last twenty years selecte upon the therm thrombocytopenic purpura...

Púrpura trombocitopénico idiopático / Idiopathic thrombocytopenic purpura

El púrpura trombocitopénico idiopático (PTI) es una enfermedad autoinmune caracterizada por recuento bajo de plaquetas y hemorragias mucocutáneas, sin alteraciones en la médula ósea y en ausencia de otras causas de trombocitopenia. En niños suele ser autolimitada, y puede ser precedida por una infección viral o una inmunización.

Rituximab in refractory autoimmune diseases: Brazilian experience with 29 patients (2002-2004).

OBJECTIVE: Rituximab, a monoclonal antibody against B-lymphocytes that express CD 20, is already available for the treatment of non-Hodgkin's lymphoma. Due to the increased relevance of B-cell regulation in the pathogenesis of autoimmune diseases, rituximab is being used in the treatment of patients whose condition is refractory to conventional therapy. METHODS: We retrospectively evaluated the short-term efficacy and tolerance of rituximab in patients with various autoimmune diseases who were treated at the Hospital Israelita Albert Einstein in the city of Sao Paulo. RESULTS: During the period 2002-2004, 29 patients with various autoimmune diseases were treated with rituximab 375 mg/m2 for 4 consecutive weeks, or two doses of 1 g 2 weeks apart. We observed remarkable short-term results in all cases, except for one patient with thrombocytopenic purpura. Of note, we describe the results in two patients with diseases not previously treated with rituximab (hypergammaglobulinemic purpura of Waldenstrom and eosinophilic fasciitis with hypergammaglobulinemia). Treatment was well tolerated, with no unexpected adverse events. We also observed a marked reduction in steroid dosage. CONCLUSION: Rituximab seems to be safe and effective in the treatment of patients with a variety of autoimmune diseases that are refractory to other modalities of treatment.

Purpura trombocitopénico idiopatico y embarazo: cesarea versus parto vaginal / Idiopathic thrombocytopenic purpura and pregnancy: cesarean section versus vaginal delivery

Si bien el púrpura trombocitopénico idiomático (PTI) es una patología poco frecuente, su importancia radica en que existe una alta morbimortalidad materno-fetal durante el embarazo, el parto y el puerperio. Es en el parto donde actualmente existe mayor controversia, con respecto a que vía es más recomendable, cesárea o vía vaginal. Nuestro propósito es acortar la brecha de la duda con respecto a ésta incógnita en base a la literatura disponible actualmente tanto a nivel nacional como internacional presentando una revisión bibliográfica sobre el PTI en el embarazo dando una pequeña reseña sobre la fisiopatología de ésta, diagnóstico y tratamiento, centrándonos en la controversia sobre que vía de parto es la más indicada. Se adoptó la estrategia de búsqueda desarrollada en la revisión electrónica de bases de datos, bajo criterios definidos que permitieron identificar los estudios con mejor evidencia posible. En nuestra búsqueda se encontraron 18 trabajos que cumplieran con nuestros criterios de búsqueda. En la literatura no encontramos un trabajo prospectivo randomizado con un buen grado de evidencia y fuerza que afirme una vía por sobre otra. Los trabajos encontrados corresponden a reportes de casos y guías de expertos que recomiendan un manejo por sobre otro. Podemos concluir que la vía del parto se definiría según condiciones obstétricas y no por el nivel de plaquetas fetales encontrados. Además, algunos de los procedimientos para determinar los niveles de plaquetas estarían relacionado a un mayor riesgo de morbimortalidad que la patología base.

Dental treatment for children with chronic idiopathic thrombocytopaenic purpura: a report of two cases.

Idiopathic thrombocytopaenic purpura (ITP) is the most common acquired bleeding disorder occurring in previously healthy children. The condition is benign and self-limiting, with a high possibility of recovery. Only 15-30% of children with acute ITP develop the chronic form. Clinically, ITP presents with petechiae, ecchymoses, haematomas, epistaxis, haematuria, mucocutaneous bleeding, and occasionally, haemorrhage into tissues. Oral manifestations include spontaneous gingival bleeding, petechiae or haematomas of the mucosa, tongue or palate. Two paediatric case reports are described concerning female patients diagnosed with chronic ITP. Oral findings and dental procedures are described. Standard dental treatment was performed with a platelet count higher than 50,000/mm3. The importance of adequate dental plaque control techniques in order to prevent inflammation, potential bleeding and infection in these patients is emphasized. The paediatric dentist must be aware of the clinical appearance of ITP in order to recognize the condition and successfully manage the patient.

Local and cultural aspects of childhood idiopathic thrombocytopenic purpura: a summary of statements from the 12 countries worldwide.

Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous bleeding disorder. The Intercontinental Childhood ITP Study Group (ICIS) analyzed demographic data and outcome in a prospective registry of over 2,000 children with ITP. In addition, participating centers from 12 different countries worldwide were asked to describe their local and cultural aspects of ITP management to provide a summary statement of the variable diagnostic and management approaches for childhood ITP. The statements of the 15 reports from 12 countries are summarized under eight main areas to reflect the variability in approach to ITP among different countries. The management of ITP in children differs dramatically worldwide in terms of observation only, medical treatment, bleeding symptoms, acceptable platelet counts, need for hospitalization or outpatient treatment, and medical care climate. The majority of experimental treatments, surveys, and guidelines are not evidence-based. Although there is a great need for cooperative studies to learn more about diagnosis, management, and prognosis in the heterogeneous disorder of ITP, local and cultural variations must be considered in international investigations.

Púrpura trombocitopênica idiopatica: estudo clínico / Idiopathic thrombocytopenic purpura: clinical study: 43 cases analize

O termo púrpura trombocitopênica idiopática (PTI) refere-se a uma trombocitopenia isolada, sem nenhuma alteração da medula óssea, na ausência de quaisquer outras causas de trombocitopenia. Os autores propõem avaliar retrospectivamente o comportamento dessa enfermidade em 43 pacientes cadastrados no Serviço de Hematologia do Hospital Universitário Alzira Velano - HUAV. Analisam e comparam diversos parâmetros pertinentes, tais como índice de remissão espontânea e cronificação da doença em relação à idade; severidade do quadro clínico em função da plaquetometria e associação de maturação microeritroblástica nos mielogramas de pacientes protadores de PTI

The clinical course of immune thrombocytopenic purpura in children who did not receive intravenous immunoglobulins or sustained prednisone treatment.

OBJECTIVE: To demonstrate the result of watchful waiting without specific therapy in unselected children with acute immune thrombocytopenic purpura (ITP). STUDY DESIGN: Between May 1992 and October 1999, 55 consecutive children (aged 2 months to 16 years; 28 boys and 27 girls) with acute ITP did not receive intravenously administered immune globulin G (IVIG) or sustained prednisone treatment. Patients with extensive mucosal bleeding were given prednisone, 2 mg/kg/d, for 3 days. RESULTS: In 37 of 55 patients the initial platelet count was <10,000/microL. Ten of these patients had active mucosal bleeding. Five additional patients with bleeding had platelet counts between 10,000 and 20,000/microL. Four patients were given a 3-day course of prednisone. Chronic ITP occurred in 7 (13%) of the patients; 29 patients achieved remission within 6 weeks, and 19 patients, between 6 weeks and 6 months. No life-threatening bleeding occurred, and no patient died. CONCLUSION: Most children with severe thrombocytopenia do not have active mucosal bleeding. This management approach, which did not administer specific therapy, avoided side effects, reduced cost, and was effective.

Treatment with liposome-encapsulated clodronate as a new strategic approach in the management of immune thrombocytopenic purpura in a mouse model.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease related to the presence of elevated levels of platelet-associated immunoglobulin, or autoantibodies. In recent years the importance of macrophage Fc gamma receptors in the uptake of platelets in ITP has been confirmed. Although in patients with ITP the platelet destruction occurs in liver and spleen, in this present experimental mouse model the liver was the principal organ of sequestration of sensitized platelets. The uptake in the spleen, bone marrow, lung, and kidneys was negligible and not different from that in control animals. In addition, the trapped platelets did not return to circulation, and new cells derived from the platelet-storage pool or new thrombocytogenesis were necessary to restore the platelet count. The depletion of splenic and hepatic murine macrophages by liposome-encapsulated clodronate (lip-clod) was studied as a new strategy for ITP treatment. Lip-clod inhibits, in a dose-dependent manner, the antibody-induced thrombocytopenia. Moreover, lip-clod treatment rapidly restored (24 hours) the platelet count in thrombocytopenic animals to hematologic safe values, and despite additional antiplatelet antiserum treatment, mice were able to maintain this level of platelets at least up to 48 hours. The bleeding times in lip-clod-treated animals was not different from those in controls, demonstrating that the hemostasis was well controlled in these animals. The results presented in this study demonstrate that lip-clod treatment can be effective in the management of experimental ITP. (Blood. 2000;96:2834-2840)

Púrpura trombocitopénica idiopática aguda en niños: un estudio prospectivo de tratamiento con y sin prednisona / Acute idiopathic thrombocytopenic purpura in children: a prospective study comparing treatment with or without prednisone

Se estudian prospectivamente 52 pacientes con púrpura trombocitopénica idiopática (PTI), cuyas edades fluctuaron entre un mes y 19 años, para evaluar la respuesta al tratamiento randomizado con y sin prednisona (PDN). 27 pacientes recibieron PDN en dosis mg/kg/día durante un mes (grupo I), y los que normalizaron el recuento plaquetario, lo hicieron en una mediana de 33 días. 25 pacientes fueron el grupo control (grupo 2), sin tratamiento, y los que normalizaron sus plaquetas, lo hicieron en una mediana de 30 días. 22 pacientes, en número equivalente de cada uno de los grupos, no recuperaron sus plaquetas en el período de 6 meses, transformándose la enfermedad en una PTI crónica. Se concluye que la normalización del recuento plaquetario es independiente del valor inicial y del uso o no uso de PDN, no modificando este medicamento la evolución natural de la enfermedad. finalmente la evolución de estos pacientes orienta a que el reposo es una medida terapéutica importante para evitar los riesgos de hemorragias