Management of a twin pregnancy patient with Glanzmann thrombasthenia might be caused by a novel ITGA2B gene mutation (c.2822G>A): a case report and family investigation.
{"title":"Management of a twin pregnancy patient with Glanzmann thrombasthenia might be caused by a novel <i>ITGA2B</i> gene mutation (c.2822G>A): a case report and family investigation.","authors":"Xiangcheng Liao, Ruikai Zhu, Zhigang Yang, Aiqiu Qin, Yucong Huang, Ping Li, Liling Liu, Zhuning Mo","doi":"10.1080/09537104.2025.2470758","DOIUrl":null,"url":null,"abstract":"<p><p>Mutations in the ITGA2B or ITGB3 gene that encodes for the αIIbβ3 platelet integrin usually cause Glanzmann thrombasthenia (GT). This study aims to investigate the clinical characteristics of a pedigree exhibiting an inherited hemorrhagic disorder resembling GT, elucidate its molecular pathogenesis and evaluate the efficacy of blood management strategies for a proband who is pregnant with twins. The clinical data of the pedigree with inherited hemorrhagic disorder were collected, including the assessment of clinical, laboratory and thromboelastography (TEG) profiles. DNA samples were obtained for next-generation sequencing, encompassing the exons and flanking sequences of the ITGA2B and ITGB3 genes, as well as other genes associated with blood and immune deficiency. Bioinformatics software tools, such as PolyPhen-2, SIFT and MutationTaster, were employed to analyze the functional impact of mutations. Protein structural models for the new mutation type were generated using PyMOL. The phenotype of the proband in this pedigree with inherited platelet dysfunction and bleeding disorder was in accordance with GT. The proband shows persistent blood accumulation in the uterine cavity. Laboratory findings indicate normal PLT morphology, PLT count, MPV, and PDW. However, there is a decreased PLT aggregation induced by agonists ADP, collagen, and AA while maintaining a normal response to ristocetin. The initial TEG examination results indicated that the patient presented with a hypocoagulable state, characterize d by a reduction in α angle (46.9), an extended K value (4.6) and a decreased maximum amplitude (35.1). The younger sister demonstrated comparable TEG performance to that of the proband and has a documented history of abnormal bleeding. A novel heterozygous mutation of <i>ITGA2B</i> at position c.2822 G>A (p.Trp941*) was identified in the proband and her familial counterparts-father, brother and sister. MutationTaster software predicted the new mutation to be pathogenic; however, PolyPhen-2 and SIFT software did not provide correlated predictions. The p.Trp941* mutation resulted in the premature termination of translation at residue 940Trp, leading to impaired protein function. Successful management was achieved during the perioperative period by administration of human immunoglobulin, platelets and antifibrinolytic drugs, followed by recombinant factor VIIa (rFVIIa), according to the thromboelastography tracings. The laboratory findings of the proband are consistent with GT, and a novel mutation in the ITGA2B gene at position c.2822 G>A (p.Trp941*) has been identified as a potential cause of GT. However, since GT is a recessive disorder and both the proband and her family members are heterozygous, it cannot be excluded that they may possess additional bleeding risk factors, including the presence of other undetected variants. This study also illustrates the significance of multidisciplinary planning, TEG analysis and judicious utilization of rFVIIa to minimize operative bleeding risk.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"36 1","pages":"2470758"},"PeriodicalIF":2.5000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Platelets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/09537104.2025.2470758","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/24 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Mutations in the ITGA2B or ITGB3 gene that encodes for the αIIbβ3 platelet integrin usually cause Glanzmann thrombasthenia (GT). This study aims to investigate the clinical characteristics of a pedigree exhibiting an inherited hemorrhagic disorder resembling GT, elucidate its molecular pathogenesis and evaluate the efficacy of blood management strategies for a proband who is pregnant with twins. The clinical data of the pedigree with inherited hemorrhagic disorder were collected, including the assessment of clinical, laboratory and thromboelastography (TEG) profiles. DNA samples were obtained for next-generation sequencing, encompassing the exons and flanking sequences of the ITGA2B and ITGB3 genes, as well as other genes associated with blood and immune deficiency. Bioinformatics software tools, such as PolyPhen-2, SIFT and MutationTaster, were employed to analyze the functional impact of mutations. Protein structural models for the new mutation type were generated using PyMOL. The phenotype of the proband in this pedigree with inherited platelet dysfunction and bleeding disorder was in accordance with GT. The proband shows persistent blood accumulation in the uterine cavity. Laboratory findings indicate normal PLT morphology, PLT count, MPV, and PDW. However, there is a decreased PLT aggregation induced by agonists ADP, collagen, and AA while maintaining a normal response to ristocetin. The initial TEG examination results indicated that the patient presented with a hypocoagulable state, characterize d by a reduction in α angle (46.9), an extended K value (4.6) and a decreased maximum amplitude (35.1). The younger sister demonstrated comparable TEG performance to that of the proband and has a documented history of abnormal bleeding. A novel heterozygous mutation of ITGA2B at position c.2822 G>A (p.Trp941*) was identified in the proband and her familial counterparts-father, brother and sister. MutationTaster software predicted the new mutation to be pathogenic; however, PolyPhen-2 and SIFT software did not provide correlated predictions. The p.Trp941* mutation resulted in the premature termination of translation at residue 940Trp, leading to impaired protein function. Successful management was achieved during the perioperative period by administration of human immunoglobulin, platelets and antifibrinolytic drugs, followed by recombinant factor VIIa (rFVIIa), according to the thromboelastography tracings. The laboratory findings of the proband are consistent with GT, and a novel mutation in the ITGA2B gene at position c.2822 G>A (p.Trp941*) has been identified as a potential cause of GT. However, since GT is a recessive disorder and both the proband and her family members are heterozygous, it cannot be excluded that they may possess additional bleeding risk factors, including the presence of other undetected variants. This study also illustrates the significance of multidisciplinary planning, TEG analysis and judicious utilization of rFVIIa to minimize operative bleeding risk.
期刊介绍:
Platelets is an international, peer-reviewed journal covering all aspects of platelet- and megakaryocyte-related research.
Platelets provides the opportunity for contributors and readers across scientific disciplines to engage with new information about blood platelets. The journal’s Methods section aims to improve standardization between laboratories and to help researchers replicate difficult methods.
Research areas include:
Platelet function
Biochemistry
Signal transduction
Pharmacology and therapeutics
Interaction with other cells in the blood vessel wall
The contribution of platelets and platelet-derived products to health and disease
The journal publishes original articles, fast-track articles, review articles, systematic reviews, methods papers, short communications, case reports, opinion articles, commentaries, gene of the issue, and letters to the editor.
Platelets operates a single-blind peer review policy. Authors can choose to publish gold open access in this journal.