Polimorfismos genéticos implicados en el desarrollo de la purpura trombocitopénica inmune / Genetic polymorphisms involved in the development of Immune Thrombocytopenic Purpura

Introducción: los cambios en el ácido desoxirribonucleico se conocen como mutaciones, estas dan lugar a los polimorfismos, los cuales generan variación alélica entre individuos y diversidad de la misma especie. Se ha sugerido que los polimorfismos genéticos en los mediadores inmunitarios desempeñan un papel fundamental en la patogénesis de muchos trastornos autoinmunes, como en la púrpura trombocitopénica inmune, siendo esta el tipo más común de púrpura trombocitopénica y, a menudo, se diagnostica como un tipo de trastorno autoinmune, debido a la destrucción de las plaquetas mediadas por el sistema inmunitario. Objetivo: realizar una revisión bibliográfica sobre el papel de los polimorfismos genéticos y su influencia en el desarrollo de la púrpura trombocitopénica inmune. Métodos: se realizó revisión literaria en inglés y español en PubMed y Elsevier, desde marzo hasta mayo del 2021, con el uso de combinación de palabras clave y términos MeSH, como púrpura trombocitopénica y polimorfismos genéticos. Se realizó análisis y resumen de la literatura encontrada. Conclusión: la púrpura trombocitopénica inmune es considerada como una patología multifactorial, causada por factores ambientales y genéticos, dentro de los cuales se encuentran los polimorfismos para los mediadores inmunitarios que pueden llevar a una exacerbación de la enfermedad o no intervenir en la misma.

Introduction: Changes in deoxyribonucleic acid are known as mutations, these give place to polymorphisms, which generate allelic variation between individuals and provide diversity among same species. Genetic polymorphisms in immune mediators have been suggested to play a key role in the pathogenesis of many autoimmune disorders, such as immune thrombocytopenic purpura, this being the most common type of thrombocytopenic purpura and is often diagnosed as a type of autoimmune disorder, due to the destruction of platelets mediated by the immune system. Objective: To execute a bibliographic review on the role of genetic polymorphisms and their influence on the development of immune thrombocytopenic purpura. Methods: A literary review in English and Spanish was performed in PubMed and Elsevier from March to May 2021, with the use of a combination of keywords and MeSH terms such as Thrombocytopenic Purpura and genetic polymorphisms. Analysis and summary of the literature found was executed. Conclusion: Immune thrombocytopenic purpura is considered a multifactorial pathology, caused by environmental and genetic factors, among which are polymorphisms for immune mediators that can lead to an exacerbation of the disease or not intervene in the same.

El volumen medioplaquetario: su importancia en la práctica clínica / Mean platelet volume: its importance in clinical practice

Las plaquetas son fragmentos citoplasmáticos anucleados derivados de los megacariocitos que presentan función central, tanto en procesos fisiológicos como la hemostasia, así como también en procesos patológicos como la inflamación, la ateroesclerosis. El tamaño de las plaquetas, medido como volumen medio de plaquetas, es un marcador de reactividad plaquetaria, que proporciona información importante sobre el curso y pronóstico de una variedad de afecciones inflamatorias. El estudio de este marcador se ha utilizado como pronóstico en enfermedades cardiovasculares, preeclampsia y en la púrpura trombocitopénica. El objetivo de este trabajo es revisar los conceptos actuales basados en la evidencia científica relacionados con el volumen plaquetario medio e insistir en su evaluación y significado en la práctica clínica cotidiana(AU)

Platelets are enucleated cytoplasmic fragments derived from megakaryocytes, which have a central function, both in physiological processes such as hemostasis, as well as in pathological processes such as inflammation, atherosclerosis. Platelet size, measured as mean volume of platelets, is a marker of platelet reactivity, providing important information on the course and prognosis of a variety of inflammatory conditions. The study of this marker has been used as a prognostic in cardiovascular diseases, preeclampsia and in thrombocytopenic purpura. The objective of this paper is to review the current concepts based on scientific evidence related to the mean platelet volume and to insist on its evaluation and meaning in daily clinical practice(AU)

Manejo oportuno de púrpura trombocitopénica trombótica en paciente con lupus eritematoso sistémico: reporte de caso / Timely management of thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus: case report

Introducción: La púrpura trombocitopénica trombótica puede presentarse en menos del 2 por ciento de los pacientes con lupus eritematoso sistémico. Esta asociación implica un aumento de la mortalidad y un periodo de remisión más prolongado. Objetivo: Se presenta el caso de paciente peruana que desarrolló esta asociación y presentó complicaciones relacionadas con shock séptico. Caso clínico: Paciente femenina, con antecedente de púrpura trombocitopénica inmunológica y lupus eritematoso sistémico, acudió a emergencia por presentar palidez cutánea generalizada, petequias en miembros inferiores y hematuria. Posteriormente, su estado de salud se complicó con un shock séptico y deterioro del nivel de conciencia. Por todo esto, es referida a un hospital de mayor complejidad y hace su ingreso a la unidad de cuidados intensivos. La clínica y los exámenes de laboratorio revelaron hallazgos compatibles con púrpura trombocitopénica trombótica (anemia grave, plaquetopenia, esquistositosis) y lupus eritematoso sistémico activo grave. Antes de ser referida, recibió pulsos de metilprednisona y prednisona. Ya en unidad de cuidados intensivos, se cambió a soporte ventilatorio y tratamiento antibiótico. Con el diagnóstico presuntivo de púrpura trombocitopénica trombótica, asociada a lupus eritematoso sistémico activo grave, se inició tratamiento oportuno con plasmaféresis, corticoterapia y ciclofosfamida. La paciente recuperó los niveles plaquetarios y el nivel óptimo de conciencia. Actualmente acude a controles. Conclusiones: La púrpura trombocitopénica trombótica es una emergencia hematológica con alta mortalidad en ausencia de tratamiento. Su reconocimiento oportuno, sin dosificación de la proteína ADAMTS13, en esta asociación poco frecuente con lupus eritematoso sistémico es importante en el buen pronóstico del paciente(AU)

Introduction: Thrombotic thrombocytopenic purpura may occur in less than 2 percent of patients with systemic lupus erythematosus. This association implies an increase in mortality and a longer remission period. Objective: We present the case of a Peruvian woman who developed this association, and complicating herself with septic shock. Clinical case: A female patient, with a history of immunological thrombocytopenic purpura and systemic lupus erythematosus, comes to the emergency room due to generalized skin pallor, lower limb petechiae and hematuria. Subsequently, her state of health gets complicated with a septic shock and deterioration of the level of consciousness. For all of this, she was referred to a hospital of greater complexity and makes admission to an intensive care unit. Clinical and laboratory tests revealed findings compatible with thrombotic thrombocytopenic purpura (severe anemia, platelet disease, schistositosis) and severe active systemic lupus erythematosus. Before being referred, she received pulses of methylprednisone and prednisone. When already in the intensive care unit, it was changed to ventilatory support andantibiotic treatment. With the presumptive diagnosis of thrombotic thrombocytopenic purpura, associated with severe active systemic lupus erythematosus, a timely treatment was initiated with plasmapheresis, corticosteroids and cyclophosphamide. The patient recovered platelet levels and optimal level of consciousness. She is currently going to controls. Conclusions: Thrombotic thrombocytopenic purpura is a hematological emergency with high mortality in the absence of treatment. Its timely recognition, without dosing of ADAMTS13 protein, in this rare association with systemic lupus erythematosus is important in the good prognosis of the patient(AU)

Quetiapine Induced Autoimmune Hemolytic Anemia in a Child Patient: A Case Report

Autoimmune hemolytic anemia is a disease characterized with destruction of erythrocytes as a result of antibody produce against patient's own erythrocytes and anemia. Autoimmune hemolytic anemia can be roughly stratified into two groups according to serological features and secondary causes including drugs induced hemolytic anemia. Drugs induced autoimmune hemolytic anemia is very rare in pediatric patients. Even though hematological side effects such as leucopenia, agranulocytosis, eosinophilia, thrombocytopenic purpura and aplastic anemia might occur due to psychotropic drug use; to the best of our knowledge there is no autoimmune hemolytic anemia case due to quetiapine, an atypical antipsychotics, in literature. We hereby describe the first child case of autoimmune hemolytic anemia during quetiapine treatment.We also are pointing out that one should keep in mind serious hematological side effects with atypical antipsychotic drug use with this case report.

Thrombocytopenic purpuraafter Influenza A H1N1 vaccine

Idiopathic thrombocytopenic purpura (ITP) is probably a disease with autoimmune etiology, defined as an isolated thrombocytopenia not associated with any clinical condition. Other causes related to thrombocytopenia are: HIV infection, systemic lupus erythematosus and druginduced thrombocytopenia. In this report we describe a case of ITP developed after vaccination against influenza A H1N1 in a 64-year-old female patient, hypertensive, offset and in use of antihypertensives, with no history of ITP, after review of clinical history and laboratory tests. The patient's physical examination revealed pallor, ecchymosis in the trunk, limbs and oral mucosa, with bleeding gums. Absence of adenomegaly and palpable splenomegaly, fever or other signs and symptoms of relevance. The blood count and bone marrow examination showed severe thrombocytopenia with platelet count of 7,000/µL and hypercellularity of the megakaryocytic series (other series were normal), respectively. A transfusion of concentrate platelet was performed and after treatment with specific poly immunoglobulin (IVIG) and corticoids, the patient showed clinical improvement and laboratory indexes were normalized. ITP after vaccine against influenza A H1N1 is a rare event whose causal relationship is difficult to prove, and the diagnosis is based on exclusion of other possible etiologies.

Trombocitopenia inmune primaria aguda presentación clínica y manejo en pacientes pediátricos, Hospital Mario Catarino Rivas / Acute primary immune thrombocytopenia clinical presentation and management in pediatric patients, Hospital Mario Catarino Rivas

Antecedentes: La trombocitopenia inmune primaria, conocida como púrpura trombocito-pénica idiopática (PTI), es un trastorno autoin-mune adquirido que afecta adultos y niños. Objetivo: Caracterizar los pacientes pediátri-cos con PTI aguda mediante su identi cación y seguimiento en el Hospital Nacional Mario Catarino Rivas (HNMCR) entre 1 febrero del 2016 al 31 enero del 2017. Pacientes y Méto-dos: Estudio cuantitativo, diseño no experi-mental longitudinal ­ prospectivo, alcance descriptivo. La población es todo paciente menor de 18 años de edad, que acudió al HNMCR con PTI aguda. La muestra 47 pacien-tes. Excluidos pacientes previamente diagnos-ticados con PTI, con segundos episodios o recaídas, con patologías sobre agregadas. Información recopilada mediante un instru-mento tipo encuesta: situación demográ ca, área geográ ca y revisión del expediente clíni-co, los datos fueron analizados con el progra-ma EPIINFO y EXCEL. Resultados: En cuanto al grupo etario el 56% fueron menores de cinco años de edad, la distribución por sexos hubo predominio del sexo masculino. 81% de los niños fueron hospitalizados, el resto recibió manejo ambulatorio; sin embargo en el 100% se inició alguna terapia con resolución de la trombocitopenia a los 3 meses. Luego del seguimiento, el diagnóstico nal de los casos captados fue PTI aguda 58%(n=27), evolucio-naron a la cronicidad 20% (n=9), el 22% (n=10) abandonaron seguimiento. Conclusiones: La mayoría de los pacientes con PTI son admitidos al hospital, aunque su conteo de plaquetas no los ponga en riesgo claro de hemorragias espontáneas, por no haber guías de manejo en nuestro hospital...(AU)

Púrpura trombocitopênica imunológica crônica e infecção pelo helicobacter pylori: respostaplaquetária ao tratamento de erradicação da bactéria

A Púrpura Trombocitopênica Imunológica Crônica (PTIc) é uma afecção causada por resposta auto-imune decorrente da sensibilização das plaquetas por auto anticorpos antiplaquetários, causando lise das plaquetas. A infecção pelo H. pylori tem sido mostrada como provável fator para o desenvolvimento de PTIc, com possível relação de resposta plaquetária na PTIc após o tratamento de erradicação da bactéria. O objetivo foi avaliar possíveis efeitos da erradicação do Helicobacter pylori no número de plaquetas dos pacientes com PTIc atendidos no Hospital Universitário Walter Cantídio. Foram convidados a participar do estudo 29 pacientes com PTIc, 15 permaneceram e todos foram tratados para o H. pylori, sendo acompanhados por um período de 6 meses a um ano para a avaliação clínica e contagem de plaquetas. Todos realizaram endoscopia digestiva para diagnóstico da infecção e, após o tratamento, realizaram teste respiratório para confirmação da erradicação. Foi realizado PCR para averiguar a presença do gene cagA do H. pylori. Dos 15 pacientes tratados 01 (6,6%) era do gênero masculino e 14 (93,3%) foram do gênero feminino, a média de idade foi de 47,7 anos (27-68), O tempo médio de doença foi de 7,43 anos (1-25)...

The Chronic Immune Thrombocytopenic Purpura ITPc) is a condition caused by autoimmune response resulting awareness of platelets by self antiplatelet antibodies, causing lysis of platelets. Infection with H. pylori has been shown to likely factor for the development of PTIc, with possible platelet response relationship in PTIc after treatment of bacterial eradication. The objective was to evaluate possible effects of eradication of Helicobacter pylori in the number of platelets of patients with PTIC patients at the University Hospital Walter Cantídio. Were invited to participate in the study 29 patients with PTIc, 15 remained and all were treatedfor H. pylori and were followed for a period of 6 months to a year for clinical evaluation and platelet count. All patients underwent endoscopy for diagnosis of infection and, after treatment, held breath test to confirm eradication. PCR was performed forthe presence of H. pyloricagA gene. Of the 15 patients 01 (6.6%) were male and 14 (93.3%) were female, the mean age was 47.7 years (27-68), the mean disease duration was 7.43 years (1-25)...

Diagnóstico y tratamiento de la púrpura trombocitopénica inmunológica / Diagnosis and treatment of Immune thrombocytopenic purpura

Desde siempre los episodios de sangrado muco-cutáneos, al ser tan evidentes, causan mucha preocupación y zozobra, más aún si ocurren sin causa aparente. La púrpura trombocitopénica suele ser la responsable de estos desagradables sucesos. Esta revisión tiene por objetivo actualizar los conocimientos acerca de la fisiopatología, el diagnóstico y el tratamiento de la púrpura trombocitopénica inmunológica (PTI), una patología hematológica que afecta tanto a niños como a adultos y que se ve con relativa frecuencia en la actividad diaria de un hospital general...

Thrombocytopenic purpura is mostly responsible for episodes of muco-cutaneous bleeding. This review updates topics on the pathophysiology, diagnosis and treatment of immunologic thrombocytopenic purpura (IPT), an hematologic condition that afects both childern and adults, which is seen relatively frequent in daily practice in a general hospital...

Anemia hemolítica microangiopática en lupus eritematoso sistémico: revisión narrativa de la literatura / Microangiopathic hemolytic anemia in systemic lupus erythematosus: narrative review

El espectro clínico de los trastornos microangiopáticos es muy amplio y se necesitade una gran habilidad clínica para determinar el origen, especialmente en el pacientecon lupus eritematoso sistémico, en quien no solo se debe considerar púrpura trombocitopénicatrombótica asociada, sino también: síndrome antifosfolípido; generalmente del tipocatastrófico; microangiopatía localizada o hipertensión maligna.Objetivo: Describir, de acuerdo con lo reportado en la literatura; la frecuencia, las causas y lascaracterísticas clínicas de la microangiopatía trombótica en lupus eritematoso sistémico.Métodos: Revisión estructurada no sistemática de la literatura.Resultados: Se incluyeron 51 artículos (42 provenientes de la búsqueda en bases de datos y9 referenciados en estos) para la revisión de los aspectos de interés mencionados...

Fatal outcome o infection by dengue 4 in a patent with thrombocytopenic purpuura as a comorbid condition in Brazil / Óbito por dengue 4 no Brasil em paciente com púrpura trombocitopênica idiopática

Dengue is currently a major public-health problem. Dengue virus (DENV) is classified into four distinct serotypes, DENV 1-4. After 28 years of absence, DENV-4 was again detected in Brazil in 2010 in Roraima State, and one year later, the virus was identified in the northern Brazilian states of Amazonas and Pará, followed by Rio de Janeiro and São Paulo. In Minas Gerais, the first confirmed case of DENV-4 occurred in the municipality of Frutal in 2011 and has now been isolated from a growing number of patients. Although DENV-2 is associated with the highest risk of severe forms of the disease and death due to the infection, DENV-4 has also been associated with severe forms of the disease and an increasing risk of hemorrhagic manifestations. Herein, the first fatal case of confirmed DENV-4 in Brazil is reported. The patient was an 11-year-old girl from the municipality of Montes Claros in northern Minas Gerais State, Brazil. She had idiopathic thrombocytopenic purpura as a comorbid condition and presented with a fulminant course of infection, leading to death due to hemorrhagic complications. Diagnosis was confirmed by detection of Dengue-specific antibodies using IgM capture enzyme-linked immunosorbent assay and semi-nested RT-PCR. Primary care physicians and other health-care providers should bear in mind that DENV-4 can also result in severe forms of the disease and lead to hemorrhagic complications and death, mainly when dengue infection is associated with coexisting conditions.

Dengue é atualmente um importante problema de saúde pública. O vírus da dengue (DENV) é classificado em quatro sorotipos distintos, DENV 1-4. Após 28 anos de ausência, o DENV-4 foi detectado novamente no Brasil em 2010 no Estado de Roraima, e um ano depois, o vírus foi identificado em outros estados do norte do país, Amazonas e Pará, seguido pelos estados do Rio de Janeiro e São Paulo. Em Minas Gerais, o primeiro caso confirmado de DENV-4 ocorreu no município de Frutal em 2011 e, desde então, o sorotipo foi isolado em um número crescente de pacientes. Apesar do DENV-2 estar associado a um maior risco de formas graves e morte, o DENV-4 também tem sido associado a casos graves e a risco aumentado de manifestações hemorrágicas. Neste relato, descrevemos o primeiro caso fatal confirmado por DENV-4 no Brasil. A paciente era uma menina de 11 anos do município de Montes Claros, no norte de Minas Gerais, Brasil. Apresentava púrpura trombocitopênica idiopática e evoluiu de forma fulminante durante a infecção por dengue, com óbito associado a complicações hemorrágicas. O diagnóstico foi confirmado pela detecção de anticorpos IgM específicos para dengue, por método imunoenzimático, e por semi-nested RT-PCR. Médicos e outros profissionais de saúde devem estar cientes que infecções por DENV-4 também podem resultar em formas graves da doença com complicações hemorrágicas e óbito, principalmente em pacientes com comorbidades.

Improvement of thrombocytopenia after treatment for Helicobacter pylori in a patient with immunologic thrombocytopenic purpura

Immune thrombocytopenic purpura is the most common autoimmune hematologic disease, affecting individuals of different ages. Recently, the bacterium Helicobacter pylori entered the list of causes of immune thrombocytopenic purpura. Here we present the case of a 55-year-old female patient with low platelet counts initially attributed to chronic vaginal bleeding. As corticosteroid therapy was ineffective she was treated for H. pylori infection. Within four weeks the patient had a platelet count of 87.17 ×109/L accompanied by clinical improvement of the symptoms.

Las trombopoyetinas en el tratamiento de la púrpura trombocitopénica inmunitaria y otras trombocitopenias / Thrombopoietines in the treatment of the thrombocytopenic purpura and other thrombocytopenics

La purpura trombocitopénica inmunitaria y las trombocitopenias secundarias representan condiciones patológicas graves cuyo tratamiento plantea diversos grados de dificultad. La aproximación terapéutica convencional ha sido la administración de esteroides, la esplenectomía y el uso de inmunoglobulina intravenosa u otros tipos de anticuerpos (e.g., anti-D). La mejor comprensión de la fisiología y fisiopatología de la trombopoyesis aunado a los avances en biología molecular ha permitido el desarrollo de una nueva aproximación terapéutica, la aplicación de las trombopoyetinas sintéticas o no inmunogénicas. Dentro de este grupo resaltan dos compuestos: el romiplostin (una proteína de fusión) y el eltrombopag (un compuesto sintético de bajo peso molecular). Ambas se encuentran disponibles comercialmente. Los estudios clínicos indican que estos medicamentos tienen un efecto satisfactorio en el tratamiento de las trombocitopenias, particularmente en los casos refractarios a los tratamientos convencionales.

Immune thrombocytopenic purpura and the secondary thrombocytopenias are conditions potentially severe with diverse degrees of treatment difficulties. Steroids administration, splenectomy and the use of intravenous immunoglobulin and other antibodies (e.g., anti-D) had been the conventional therapy. The better understanding of the thrombopoiesis physiology and physiopathology togetter with the biology advances have permitted the development of a new terapheutic approach: the use of synthetic or nonimmunogenic thrombopoietines. Among this group highlights composites: romiplostim (a fusion protein) and eltrombopag (a synthetic composite with low molecular wheigt). Both are already available and produce a satisfactory effect particularly in nonrespondent cases to the conventional treatment.

Ludwig's angina after severe thrombocytopenic purpura associated with dengue fever

Here, we report a case of Ludwig's angina, which required surgery because of toothache. The patient had dengue and severe thrombocytopenia as confirmed by clinical and laboratory diagnoses. However, dengue is not included among the predisposing factors for Ludwig's angina.

La trombocitopenia inmune como manifestación de la infección por Helicobacter pylori / Immune thrombocytopenia as a manifestation of Helicobacter pylori infection

Resumen: Helicobacter pylori es el agente causal de la infección más frecuente de la especie humana, con una marcada desventaja entre los países desarrollados y los países en vía de desarrollo. Si bien, la infección por Helicobacter pylori cursa asintomática en la mayoría de los individuos infectados, también es claro que está íntimamente relacionada con enfermedades malignas del estómago como el cáncer gástrico y el linfoma MALT gástrico; y enfermedades benignas como la gastritis crónica y la úlcera péptica duodenal y gástrica. A partir del momento en que se conoció que la mucosa gástrica podía ser colonizada por una bacteria, en la literatura médica mundial indexada (PubMed) se han informado alrededor de una centena de manifestaciones extragástricas que involucran a especialidades médicas tan disímiles como la cardiología, la dermatología, la endocrinología, la ginecobstetricia, la hematología, la neumología, la neurología, la odontología, la oftalmología, la otorrinolaringología, la pediatría, la siquiatría y vascular periférico, algunas de ellas con mayor o menor acervo probatorio entre la infección por Helicobacter pylori y el desarrollo de la enfermedad. Esta revisión de la literatura médica mundial se centra en el análisis de la relación de la infección por Helicobacter pylori con la trombocitopenia inmune (ITP), antes conocida como púrpura trombocitopénica idiopática. Se presenta una visión global de la ITP, las evidencias de la asociación con la infección por Helicobacter pylori, la fisiopatología y el manejo de ésta en la era poshelicobacter.

Abstract: Helicobacter pylori is the most common causative agent of human infection, with a marked disadvantage between developed and developing countries. Although Helicobacter pylori infection is asymptomatic in majority of individuals infected, it is also clear their close relation with malignant diseases of the stomach as gastric cancer and gastric MALT lymphoma and benign diseases such as chronic gastritis and duodenal and gastric peptic ulcer. Since the moment it became know that bacteria could colonize the gastric mucosa, hundred extragastric events have been reported in the indexed world medical literature (PubMed), that involves medical specialties as diverse as cardiology, dermatology, endocrinology, obstetrics and gynecology, hematology, pulmonology, neurology, dentistry, ophthalmology, otolaryngology, pediatrics, psychiatry and peripheral vascular. Some of these with varying proofs of relation between Helicobacter pylori infection and disease development. This review focuses in the analysis of the relationship between Helicobacter pylori infection and immune thrombocytopenia (ITP), known as idiopathic thrombocytopenic purpura. The information for ITP includes the problem overview, evidence of the association with Helicobacter pylori infection, the pathophysiology and managementin poshelicobacter era.

Human Platelet Antigen Genotyping Using a Multiplex Single-Base Primer Extension Reaction in Koreans / 대한수혈학회지

BACKGROUND: Alloimmunization of human platelet antigens (HPA) is associated with clinically significant disease, such as platelet refractoriness, neonatal alloimmune thrombocytopenia, or posttransfusion purpura. It is determined by single nucleotide polymorphism of genes for platelet membrane glycoprotein. To date, approximately 27 HPAs have been discovered, and their frequencies differ depending on ethnicity and country. METHODS: We conducted an investigation of prevalence of HPA in the Korean population using a multiplex single-base primer extension reaction (SNaPshot). With 84 specimens from healthy donors, HPA genotyping was performed on 11 different HPAs, including HPA-1, -2, -3, -4, -5, -6, -7, -8, -9, -13, and -15. RESULTS: A total of 90 blood samples were genotyped. The genotype frequencies of HPA were as follows: HPA-1a/1a: 100.0%, -2a/2a: 83.3%, -2a/2b: 14.3%, -2b/2b: 2.4%, -3a/3a: 39.3%, -3a/3b: 52.4%, -3b/3b: 8.3%, -4a/4a: 100.0%, -5a/5a: 95.2%, -5a/5b: 4.8%, -6a/6a: 94.0%, -6a/6b: 6.0%, -7a/7a: 100.0%, -8a/8a: 100.0%, -9a/9a: 97.6%, -9a/9b: 2.4%, -13a/13a: 100.0%, -15a/15a: 23.8%, -15a/15b: 51.2%, and -15b/15b: 25.0%. CONCLUSION: The SNaPshot assay was employed for detection of SNPs in various clinically significant HPA genes. In addition to well-known frequencies of previously reported HPA-1 to -8, this study showed frequencies of HPA-9, -13, and -15 in Koreans for the first time. The SNaPshot technique might be suitable for use in actual clinical testing in patients with platelet alloimmunization.

Values of transforming growth factor beta-1, thrombopoietin and interleukin-6 in regulation of megakaryopoiesis in various platelets disorders

Megakaryopoiesis requires a highly complex series of cellular events in which a hematopoietic stem cell generates a cascade of committed progenitors and culminates with the production of circulating blood platelets. Megakaryopoiesis is regulated by several factors and cytokines that affect the proliferation and differentiation of megakaryopoietic cells. The aim of this study was to evaluate the role of some cytokines namely Thrombopoietin [TPO], Transforming growth factor [TGF-beta1] and lnterleukin 6 [IL-6] in regulation of megakaryopoiesis in various platelet disorders. This study was conducted on 72 patients with various platelet disorders; they were either thrombocytopenic [ITP "group I" or liver cirrhosis [LC] "group II" patients] or they presented with reactive thrombocytosis "group III". [According to modified Child classification group II patients was divided into three subgroups; Child A, Child B and Child C]. Twelve apparently healthy volunteers were included in the study for comparison. Estimations of serum TPO level, TGF-beta1 level and IL-6 level by ELISA technique were done for all studied groups. A highly significant increase in TPO and significant increase in IL-6 levels was noted in ITP group compared with the control group while TGF-beta1 was non significantly increased. In LC group and subgroups [Child A] a significant increase in TPO was noted on comparing with the control group but non significant increase in Child B and C; with progressive decrease of TPO level from Child A to Child B and Child C respectively. In LC group and Child C and B the TGF-beta1 was highly significantly increased on comparing with control group. Also it was significant increased in Child A when compared with control group i.e. there was progressive increase in TGF-beta1 with the progression of liver damage. A significant reduction in IL-6 was noted in LC group on comparing with the control group. A non significant reduction in IL-6 was noted in Child A, B and C group on comparing to the control group. In thrombocytosis group a significant increase in TPO, TGF-beta1 and IL-6 levels were noted compared to the control group. Estimation of serum TPO in ITP, liver cirrhosis and reactive thrombocytosis seems to be of benefit in diagnosis and evaluation of megakaryopoiesis state in these platelet disorders. Also estimation of TGF- beta1 can be used as good indicator of liver disease progress. TGF-beta1 was increased in thrombocytosis and this makes highlight to its role in feed back inhibition of megakaryopoiesis. Serum IL-6 was significantly increased in reactive thrombocytosis and this may confirm its role in stimulation of megakaryopoiesis