Progress of hereditary thrombocytopenia in children / 国际儿科学杂志

Hereditary thrombocytopenia(HT)is a hemorrhagic disease characterized by thrombocytopenia caused by genetic variation.HT can be manifested as simple thrombocytopenia or combined syndrome, and its clinical manifestations are complex.It often occurs in children.The unique clinical characteristics of HT are platelet dysfunction, unstable course of the disease and susceptibility to other diseases.Due to different pathogenic genes, the treatment and prognosis of HT are diverse.The evaluation of hemorrhage in the clinical management of HT children is very important.In addition, platelet transfusion, thrombopoietin receptor agonists, hematopoietic stem cell transplantation and gene therapy also supply new ideas for HT treatment.This review summarized the current research progress on HT, in order to help clinicians comprehensively identify HT and take active and effective treatment programs.

Application of high-throughput sequencing for hereditary thrombocytopenia in southwestern China.

BACKGROUND: The aim of this study was to design and analyze the applicability of a 21-gene high-throughput sequencing (HTS) panel in the molecular diagnosis of patients with hereditary thrombocytopenia (HT). METHODS: A custom target enrichment library was designed to capture 21 genes known to be associated with HTs. Twenty-four patients with an HT phenotype were studied using this technology. RESULTS: One pathogenic variant on the MYH9 gene and one likely pathogenic variant on the ABCG8 gene previously known to cause HTs were identified. Additionally, 3 previously reported variants affecting WAS, ADAMTS13, and GP1BA were detected, and 9 novel variants affecting FLNA, ITGB3, NBEAL2, MYH9, VWF, and ANKRD26 genes were identified. The 12 variants were classified to be of uncertain significance. CONCLUSION: Our results demonstrate that HTS is an accurate and reliable method of pre-screening patients for variants in known HT-causing genes. With the advantage of distinguishing HT from immune thrombocytopenia, HTS could play a key role in improving the clinical management of patients.

Genome-wide linkage analysis and whole-exome sequencing identifies an ITGA2B mutation in a family with thrombocytopenia.

Hereditary thrombocytopenias can be subclassified based on mode of inheritance and platelet size. Here we report a family with autosomal dominant (AD) thrombocytopenia with normal platelet size. Linkage analysis and whole exome sequencing identified the R1026W substitution in ITGA2B as the causative defect. The same mutation has been previously reported in 7 Japanese families/patients with AD thrombocytopenia, but all of these patients had macrothrombocytopenia. This is the first report of a family with AD thrombocytopenia with normal platelet size resulting from mutation in ITGA2B. ITGA2B mutations should therefore be included in the differential diagnosis of this latter disorder.

Single-center clinical analysis of hereditary thrombocytopenia in children with chronic thrombocytopenia / 中华实用儿科临床杂志

Objective To know the detection rate of hereditary thrombocytopenia (HT) in children with chronic thrombocytopenia and its clinical and laboratory characteristics for an early clinical identification and diagnosis of HT in future.Methods Data of the children with thrombocytopenia,who had been treated in Beijing Children's Hospital from April 2016 to May 2018 and whose present history lasted for more than 1 year and had poor response to immunotherapy were retrospectively collected.HT was screened in these patients by adopting next generation sequencing (NGS).Finally,clinical and laboratory characteristics of these children with HT were summarized and analyzed.Results A total of 161 children with chronic thrombocytopenia were included.Forty-three cases (26.7％) were found to have gene mutations.The genetic rules of the mutant gene,the family verification and the clinical manifestations of the proband and some related laboratory tests were analyzed and 24 cases (14.9％) can be diagnosed as HT.Among the HT patients,the proportion of males and females was 15 ∶ 9,and the median onset of age was 0.58 years,which was significantly lower than that of non-HT cases (the median onset of age was 4.36 years),and the difference was statistically significant (P ＜ 0.001);the proportion of mucosal hemorrhage and visceral hemorrhage (31.8％ and 13.7％) of HT was significantly higher than non-HT cases (15.3％ and 0.6％),and the difference was statistically significant (P ＜ 0.001).Fifty percent of (12/24 cases) cases of HT had positive family history;according to the average platelet volume and platelet morphology in peripheral blood smear,HT could be divided into small platelet HT,positive platelet HT and large platelet HT.Some cases had well response to immunotherapy but seemed easy to relapse during the withdrawal period,while the others responded poorly to therapy.Different clinical manifestations of HT suggest different pathogenesis,which can be divided into the related types of megakaryocyte differentiation defect,megakaryocyte maturation defect,platelet release defect and platelet survival time shortening.Conclusions The pathogenesis and clinical phenotype of HT was different.Some of them were effective for immunotherapy,which were easily confused with immune thrombocy-topenla(ITP).It is clinically necessary to perform NGS in children with thrombocytopenia at early onset,abnormal platelet morphology,prolonged disease course or severe mucosal/visceral hemorrhage,in order to recognize HT timely to avoid delay in diagnosis and poor prognosis.

Single-center clinical analysis of hereditary thrombocytopenia in children with chronic thrombocytopenia / 中华实用儿科临床杂志

Objective@#To know the detection rate of hereditary thrombocytopenia (HT) in children with chronic thrombocytopenia and its clinical and laboratory characteristics for an early clinical identification and diagnosis of HT in future.@*Methods@#Data of the children with thrombocytopenia, who had been treated in Beijing Children′s Hospital from April 2016 to May 2018 and whose present history lasted for more than 1 year and had poor response to immunotherapy were retrospectively collected.HT was screened in these patients by adopting next generation sequencing (NGS). Finally, clinical and laboratory characteristics of these children with HT were summarized and analyzed.@*Results@#A total of 161 children with chronic thrombocytopenia were included.Forty-three cases (26.7%) were found to have gene mutations.The genetic rules of the mutant gene, the family verification and the clinical manifestations of the proband and some related laboratory tests were analyzed and 24 cases (14.9%) can be diagnosed as HT.Among the HT patients, the proportion of males and females was 159, and the median onset of age was 0.58 years, which was significantly lower than that of non-HT cases (the median onset of age was 4.36 years), and the difference was statistically significant (P<0.001); the proportion of mucosal hemorrhage and visceral hemorrhage (31.8% and 13.7%) of HT was significantly higher than non-HT cases (15.3% and 0.6%), and the difference was statistically significant (P<0.001). Fifty percent of (12/24 cases) cases of HT had positive family history; according to the ave-rage platelet volume and platelet morphology in peripheral blood smear, HT could be divided into small platelet HT, po-sitive platelet HT and large platelet HT.Some cases had well response to immunotherapy but seemed easy to relapse du-ring the withdrawal period, while the others responded poorly to therapy.Different clinical manifestations of HT suggest different pathogenesis, which can be divided into the related types of megakaryocyte differentiation defect, megakaryocyte maturation defect, platelet release defect and platelet survival time shortening.@*Conclusions@#The pathogenesis and cli-nical phenotype of HT was different.Some of them were effective for immunotherapy, which were easily confused with immune thrombocy-topenla(ITP). It is clinically necessary to perform NGS in children with thrombocytopenia at early onset, abnormal platelet morphology, prolonged disease course or severe mucosal/visceral hemorrhage, in order to recognize HT timely to avoid delay in diagnosis and poor prognosis.

Inherited Thrombocytopenia with a Different Type of Gene Mutation: A Brief Literature Review and Two Case Studies.

Hereditary thrombocytopenias are rare bleeding disorders, which cause a deficiency of platelets in early infancy. This group of disorders is sometimes associated with abnormal phenotypes, like absence of radius. Diagnosis of this type of thrombocytopenia is usually difficult; other causes of thrombocytopenia, such as immune disorders and infections, must be ruled out. The symptoms of hereditary thrombocytopenia also vary from seldom and mild to severe bleeding and occasionally may first occur in late childhood. In this group of patients, we must differentiate heritable disorders from the acquired types of thrombocytopenia, like immune thrombocytopenic purpura. It is also important to watch for pitfalls to avoid unnecessary and potentially hazardous treatment. Herein, we briefly review the recent literature on hereditary thrombocytopenia and then present the cases of two referred patients. The first case had suffered from persistent thrombocytopenia since early infancy and was diagnosed with congenital amegakaryocytic thrombocytopenia, while the other patient presented with Wiskott - Aldrich syndrome.