1,543 results match your criteria Glanzmann Thrombasthenia


New αIIbβ3 variants in 28 Turkish Glanzmann patients; Structural hypothesis for complex activation by residues variations in I-EGF domains.

Platelets 2021 Jul 19:1-11. Epub 2021 Jul 19.

Département d'Immunologie Plaquettaire, Institut National De La Transfusion Sanguine (INTS), Paris, France.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by impaired platelet aggregation due to defects in integrin αIIbβ3, a fibrinogen receptor. Platelet phenotypes and allelic variations in 28 Turkish GT patients are reported. Platelets αIIbβ3 expression was evaluated by flow cytometry. Read More

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Profiling the Genetic and Molecular Characteristics of Glanzmann Thrombasthenia: Can It Guide Current and Future Therapies?

Authors:
Alan Nurden

J Blood Med 2021 8;12:581-599. Epub 2021 Jul 8.

Institut Hospitalo-Universitaire LIRYC, Pessac, France.

Glanzmann thrombasthenia (GT) is the most widely studied inherited disease of platelet function. Platelets fail to aggregate due to a defect in platelet-to-platelet attachment. The hemostatic plug fails to form and a moderate to severe bleeding diathesis results. Read More

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Next-Generation Sequencing Based Approach to Identify Underlying Genetic Defects of Glanzmann Thrombasthenia.

Indian J Hematol Blood Transfus 2021 Jul 24;37(3):414-421. Epub 2020 Oct 24.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012 India.

Glanzmann thrombasthenia (GT) is an autosomal recessive platelet function disorder characterized by mucocutaneous bleeding as the most common clinical phenotype. Patients with GT have normal platelet counts, platelet morphology but reduced platelet aggregation in response to various agonists. Homozygosity or compound heterozygosity for variants in the genes is the genetic basis for GT. Read More

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A comparative study between light transmission aggregometry and flow cytometric platelet aggregation test for the identification of platelet function defects in patients with bleeding.

Blood Res 2021 Jun;56(2):109-118

Department of Hematology, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Platelet aggregation studies using conventional light transmission aggregometry (LTA) have several disadvantages and require strict pre-analytical measures for reliable results. We aimed to examine the utility of flow cytometric platelet aggregation (FCA) assay in detecting platelet function defects (PFDs) in patients with a history of bleeding symptoms.

Methods: Sixty-four participants (24 patients and 40 healthy controls) were included in this study. Read More

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Glanzmann Thrombasthenia: Perspectives from Clinical Practice on Accurate Diagnosis and Optimal Treatment Strategies.

J Blood Med 2021 11;12:449-463. Epub 2021 Jun 11.

Division of Hematology-Oncology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, H3T 1C5, Canada.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder of fibrinogen-mediated platelet aggregation due to a quantitative or qualitative deficit of the αβ integrin at the platelet surface membrane resulting from mutation(s) in and/or . Patients tend to present in early childhood with easy bruising and mucocutaneous bleeding. The diagnostic process requires consideration of more common disorders of haemostasis and coagulation prior to confirming the disorder with platelet light transmission aggregation, flow cytometry of CD41 and CD61 expression, and/or exon sequencing of and . Read More

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Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG).

Genes (Basel) 2021 May 6;12(5). Epub 2021 May 6.

Green Cross Genome, Yongin 16924, Korea.

The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Read More

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A refugee child with multiple patterned ecchymoses: a diagnostic dilemma between nonaccidental injury and primary hemostatic defect.

Blood Coagul Fibrinolysis 2021 May 10. Epub 2021 May 10.

Department of Pediatrics, Faculty of Medicine, School of Health Sciences, University of Ioannina Molecular Biology Laboratory, Ioannina University Hospital, Ioannina Haemophilia Centre- Haemostasis and Thrombosis Unit, 'Aghia Sophia' Children's Hospital, Athens, Greece.

A 4-year-old girl from Syria presented to the hospital with multiple bruises on her body. Bruises were observed in protected areas in a shape of fingerprints and objects, while no other bruises occurred during hospitalization. The parents also reported a history of bleeding diathesis from infancy. Read More

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Flow cytometric analysis of platelet surface glycoproteins in the diagnosis of thirty-two Turkish patients with Glanzmann Thrombasthenia: a multicenter experience.

Turk J Med Sci 2021 May 7. Epub 2021 May 7.

Background/aim: Glanzmann thrombasthenia (GT) is a rare autosomal recessively inherited bleeding disorder characterized by the quantitative (type 1 and type 2) or qualitative (type 3) deficiency in platelet membrane glycoprotein (GP) IIb/IIIa (CD41a/CD61) fibrinogen receptors. In type 1, 2 and 3, CD41a/CD61 expression is 5%, 5-20% and above 20%, respectively. In this study, diagnosis of GT was confirmed and subgroups were identified in 32 Turkish patients by flow cytometry analysis. Read More

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Nonsense-mediated mRNA decay efficiency influences bleeding severity in ITGA2B c.2659C > T (p.Q887X) knock-in mice.

Clin Genet 2021 Aug 5;100(2):213-218. Epub 2021 May 5.

Hematology department, Affiliated Hospital of Nantong University, Nantong, China.

Glanzmann's thrombasthenia (GT) is a severe hemorrhagic disease. It is caused by mutations in ITGA2B or ITGB3, which are the respective genes encoding integrin αIIb and β3. Despite widespread mutational analysis, the mechanisms underlying the extensive variability in bleeding severity observed among affected individuals remains poorly understood. Read More

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Itgb3-integrin-deficient mice may not be a sufficient model for patients with Glanzmann thrombasthenia.

Mol Med Rep 2021 06 21;23(6). Epub 2021 Apr 21.

Department of Hematology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.

Itgb3‑integrin‑deficient (Itgb3) mice have been reported as a Glanzmann thrombasthenia (GT) model and have been used for platelet research. However, it remains unclear whether this mouse model can fully simulate patients with GT or whether it has different characteristics from these patients. The present study aimed to answer this question. Read More

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Weekly low-dose recombinant factor VIIa prophylaxis in Glanzmann thrombasthenia.

Blood Coagul Fibrinolysis 2021 Jul;32(5):349-351

Hematology Division, Osmangazi University Medical School, Meşelik Campus, Eskişehir, Turkey.

Glanzmann thrombasthenia is an inherited disease causing bleeding episodes due to platelet dysfunction. The standard treatment for moderate-severe bleeding is platelet transfusion. Recombinant factor VIIa (rFVIIa) is successfully used in bleeding episodes and invasive procedures. Read More

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Mutations in RASGRP2 gene identified in patients misdiagnosed as Glanzmann thrombasthenia patients.

Blood Cells Mol Dis 2021 07 4;89:102560. Epub 2021 Mar 4.

The Israeli National Hemophilia Center and Thrombosis Institute, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Introduction: Glanzmann thrombasthenia (GT) is a severe inherited platelet function disorder (IPFD), presenting with bleeding diathesis and impaired platelet aggregation, is caused by mutations in the genes ITGA2B or ITGB3.

Aim: We aimed to study the genetic cause of IPFD mimicking GT.

Methods: During 2017-2019, 16 patients were referred to our tertiary center with bleeding symptoms, impaired platelet aggregation and normal platelet count and size. Read More

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Inherited Bleeding Disorders in Pediatric Patients; experience of the national referral center in Iraq.

Indian J Hematol Blood Transfus 2021 Jan 10;37(1):96-100. Epub 2020 Jun 10.

The National Center of Hematology, Mustansiriyah University, Baghdad, Iraq.

Background: Inherited bleeding disorders can lead to lifelong bleeding; they are mainly caused by quantitative or qualitative defect of coagulation factors, von Willebrand factor (VWF) or platelets. No published data are available about the different types of inherited bleeding disorders in Iraq.

Objectives: To describe types, severity and presentation of inherited bleeding disorders in pediatric patients in the major referral center in Iraq. Read More

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January 2021

Gene Therapy for Inherited Bleeding Disorders.

Semin Thromb Hemost 2021 Mar 26;47(2):161-173. Epub 2021 Feb 26.

Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Decades of preclinical and clinical studies developing gene therapy for hemophilia are poised to bear fruit with current promising pivotal studies likely to lead to regulatory approval. However, this recent success should not obscure the multiple challenges that were overcome to reach this destination. Gene therapy for hemophilia A and B benefited from advancements in the general gene therapy field, such as the development of adeno-associated viral vectors, as well as disease-specific breakthroughs, like the identification of B-domain deleted factor VIII and hyperactive factor IX Padua. Read More

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Use of rFVIIa in Preventing Recurrent Intra-articular Hemorrhages in a 15-Year-Old Patient With Glanzmann Thrombasthenia.

Authors:
Pawel Laguna

J Pediatr Hematol Oncol 2021 Mar 31. Epub 2021 Mar 31.

Department of Oncology, Haematology, Bone Marrow Transplantation and Paediatrics, Medical University of Warsaw, Warsaw, Poland.

Glanzmann thrombasthenia is a rare congenital thrombocytopathy. The first-line treatment in severe life-threatening bleeding is a transfusion of platelet concentrate or recombinant factor VIIa in the case of platelet transfusion refractoriness. We present the case of a 16-year-old boy with Glanzmann thrombasthenia who was admitted to hospital with severe bleeding into the quadriceps femoris muscle. Read More

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A novel frameshift mutation in the ITGB3 gene leading to Glanzmann's thrombasthenia in a Saudi Arabian family.

Hematol Oncol Stem Cell Ther 2021 Feb 11. Epub 2021 Feb 11.

Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Medina, Saudi Arabia. Electronic address:

Glanzmann's thrombasthenia (GT) is an autosomal recessive congenital bleeding disorder of platelet aggregation. Mutations in ITGA2B and ITGB3 genes result in quantitative and/or qualitative abnormalities of the glycoprotein receptor complex IIb/IIIa (integrin αIIbβ3), which in turn impairs platelet aggregation and lead to GT. In this study, whole genome single nucleotide polymorphism (SNP) genotyping as well as whole exome sequencing was performed in a large family segregating GT. Read More

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February 2021

Specifications of the variant curation guidelines for ITGA2B/ITGB3: ClinGen Platelet Disorder Variant Curation Panel.

Blood Adv 2021 01;5(2):414-431

Division of Pediatric Hematology Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.

Accurate and consistent sequence variant interpretation is critical to the correct diagnosis and appropriate clinical management and counseling of patients with inherited genetic disorders. To minimize discrepancies in variant curation and classification among different clinical laboratories, the American College of Medical Genetics and Genomics (ACMG), along with the Association for Molecular Pathology (AMP), published standards and guidelines for the interpretation of sequence variants in 2015. Because the rules are not universally applicable to different genes or disorders, the Clinical Genome Resource (ClinGen) Platelet Disorder Expert Panel (PD-EP) has been tasked to make ACMG/AMP rule specifications for inherited platelet disorders. Read More

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January 2021

Prevalence of Coagulation Factors Deficiency among Young Adults in Saudi Arabia: A National Survey.

TH Open 2020 Oct 23;4(4):e457-e462. Epub 2020 Dec 23.

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Alfaisal University, Riyadh, Saudi Arabia.

 Inherited bleeding disorders vary in prevalence due to genetic disparity and ethnicity. Little is known about the prevalence of coagulation factor deficiency and bleeding disorders in middle-eastern population.  Young Saudi adults with at least one positive bleeding symptom reported in semi-structured validated condensed MCMDM-1vWD questionnaire were tested for complete blood count, routine and special coagulation tests, serum ferritin level, and capillary zone electrophoresis. Read More

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October 2020

Utility of the Platelet Function Analyzer in Patients with Suspected Platelet Function Disorders: Diagnostic Accuracy Study.

TH Open 2020 Oct 22;4(4):e427-e436. Epub 2020 Dec 22.

Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.

 The platelet function analyzer (PFA) is widely used as a screening tool for bleeding disorders in various settings. The diagnostic performance regarding platelet function disorders (PFDs), which are among the most common inherited bleeding disorders, is however still elusive. We aimed to assess the diagnostic value of PFA for PFD in clinical practice. Read More

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October 2020

Characterization of Procoagulant COAT Platelets in Patients with Glanzmann Thrombasthenia.

Int J Mol Sci 2020 Dec 14;21(24). Epub 2020 Dec 14.

Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.

Patients affected by the rare Glanzmann thrombasthenia (GT) suffer from defective or low levels of the platelet-associated glycoprotein (GP) IIb/IIIa, which acts as a fibrinogen receptor, and have therefore an impaired ability to aggregate platelets. Because the procoagulant activity is a dichotomous facet of platelet activation, diverging from the aggregation endpoint, we were interested in characterizing the ability to generate procoagulant platelets in GT patients. Therefore, we investigated, by flow cytometry analysis, platelet functions in three GT patients as well as their ability to generate procoagulant collagen-and-thrombin (COAT) platelets upon combined activation with convulxin-plus-thrombin. Read More

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December 2020

αIIbβ3 variants in ten families with autosomal dominant macrothrombocytopenia: Expanding the mutational and clinical spectrum.

PLoS One 2020 4;15(12):e0235136. Epub 2020 Dec 4.

Unidade Multidisciplinar de Investigação Biomédica, Instituto de Ciências Biomédicas, Universidade do Porto (UMIB/ICBAS/UP), Porto, Portugal.

Background: Rare pathogenic variants in either the ITGA2B or ITGB3 genes have been linked to autosomal dominant macrothrombocytopenia associated with abnormal platelet production and function, deserving the designation of Glanzmann Thrombasthenia-Like Syndrome (GTLS) or ITGA2B/ITGB3-related thrombocytopenia.

Objectives: To describe a series of patients with familial macrothrombocytopenia and decreased expression of αIIbβ3 integrin due to defects in the ITGA2B or ITGB3 genes.

Methods: We reviewed the clinical and laboratory records of 10 Portuguese families with GTLS (33 patients and 11 unaffected relatives), including the functional and genetic defects. Read More

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January 2021

A Comprehensive Review of Congenital Platelet Disorders, Thrombocytopenias and Thrombocytopathies.

Cureus 2020 Oct 31;12(10):e11275. Epub 2020 Oct 31.

Internal Medicine, ProMedica Toledo Hospital, Toledo, USA.

Platelets play an important role in hemostasis through platelet plug formation by a phenomenon of adhesion; activation; secretion and aggregation. Defects in platelet hemostatic mechanisms can be congenital or acquired. Congenital platelet disorders are rare and manifestations range from asymptomatic to sometimes severe bleeding. Read More

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October 2020

Nonredundant Roles of Platelet Glycoprotein VI and Integrin αIIbβ3 in Fibrin-Mediated Microthrombus Formation.

Arterioscler Thromb Vasc Biol 2021 02 3;41(2):e97-e111. Epub 2020 Dec 3.

Department of Biochemistry, CARIM, Maastricht University, the Netherlands (G.P., J.H., I.P., F.S., P.E.J.v.d.M., R.A.S.A., S.P.W., J.W.M.H.).

Objective: Fibrin is considered to strengthen thrombus formation via integrin αIIbβ3, but recent findings indicate that fibrin can also act as ligand for platelet glycoprotein VI. Approach and Results: To investigate the thrombus-forming potential of fibrin and the roles of platelet receptors herein, we generated a range of immobilized fibrin surfaces, some of which were cross-linked with factor XIIIa and contained VWF-BP (von Willebrand factor-binding peptide). Multicolor microfluidics assays with whole-blood flowed at high shear rate (1000 s) indicated that the fibrin surfaces, regardless of the presence of factor XIIIa or VWF-BP, supported platelet adhesion and activation (P-selectin expression), but only microthrombi were formed consisting of bilayers of platelets. Read More

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February 2021

Difficulty in controlling heavy menstrual bleeding at menarche in a patient with Glanzmann's thrombasthenia.

Blood Coagul Fibrinolysis 2021 Mar;32(2):155-158

Department of Pediatrics.

Glanzmann's thrombasthenia is a rare inherited autosomal recessive bleeding disorder caused by platelet dysfunction. Adolescent girls with Glanzmann's thrombasthenia may experience problematic heavy menstrual bleeding beginning at menarche; this can be difficult to manage. Here, we report the case of an 11-year-old girl with Glanzmann's thrombasthenia who presented with heavy menstrual bleeding at menarche, which was difficult to control. Read More

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A novel heterozygous mutation flanking the fourth calcium-binding domain of the ITGA2B gene induces severe bleeding complications: a case report and literature review.

Blood Coagul Fibrinolysis 2021 Mar;32(2):146-150

Department of Hematology and Oncology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, PR China.

Glanzmann thrombasthenia is a rare autosomal recessive genetic disease characterized by platelet aggregation dysfunction caused by a congenital defect of platelet membrane glycoprotein IIb/IIIa (integrin αIIbβ3). Integrin αIIbβ3, a calcium-dependent heterodimer, plays a critical role in platelet aggregation. We described a boy who was hospitalized with serious epistaxis at 10 months of age who had a history of repeated petechiae and spontaneous epistaxis since birth. Read More

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Glanzmann's thrombasthenia: a rare bleeding disorder in a Nigerian girl.

Afr Health Sci 2020 Jun;20(2):753-757

Department of Paediatrics, College of Medicine, University of Nigeria, Enugu Campus, Nigeria.

Introduction: Glanzmann's Thrombasthenia (GT) is a rare autosomal recessive bleeding disorder due to defective platelet membrane glycoprotein GP IIb/IIIa (integrin αIIbβ3). The prevalence is estimated at 1:1,000,000 and it is commonly seen in areas where consanguinity is high.

Case Presentation: The authors report a 12 year old Nigerian girl of Igbo ethnic group, born of non-consanguineous parents, who presented with prolonged heavy menstrual bleeding which started at menarche 3 months earlier, weakness and dizziness. Read More

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Inherited platelet diseases with normal platelet count: phenotypes, genotypes and diagnostic strategy.

Haematologica 2021 02 1;106(2):337-350. Epub 2021 Feb 1.

Institut Hospitalo-Universitaire LIRYC, Pessac.

Inherited platelet disorders resulting from platelet function defects and a normal platelet count cause a moderate or severe bleeding diathesis. Since the description of Glanzmann thrombasthenia resulting from defects of ITGA2B and ITGB3, new inherited platelet disorders have been discovered, facilitated by the use of high throughput sequencing and genomic analyses. Defects of RASGRP2 and FERMT3 responsible for severe bleeding syndromes and integrin activation have illustrated the critical role of signaling molecules. Read More

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February 2021

The Use of Recombinant Activated Factor VII in Patients with Glanzmann's Thrombasthenia.

Authors:
Man-Chiu Poon

Thromb Haemost 2021 Mar 29;121(3):332-340. Epub 2020 Oct 29.

Department of Medicine, Pediatrics and Oncology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.

Platelet transfusion is the standard treatment to control or prevent bleeding in patients with Glanzmann's thrombasthenia (GT), but platelets are often unavailable. Recombinant activated factor VII (rFVIIa) is an effective alternative to platelets in patients with GT with past/present refractoriness to platelet transfusions and antibodies to platelets. However, there is an unmet need for an alternative to platelets in patients without antibodies. Read More

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Why thromboembolism occurs in some patients with thrombocytopenia and treatment strategies.

Thromb Res 2020 12 8;196:500-509. Epub 2020 Oct 8.

Department of Cardiovascular Center, Jilin University First Hospital, China. Electronic address:

Platelets play such an important role in the process of thrombosis that patients with thrombocytopenia generally have an increased risk of bleeding. However, abnormal thrombotic events can sometimes occur in patients with thrombocytopenia, which is unusual and inexplicable. The treatments for thrombocytopenia and thromboembolism are usually contradictory. Read More

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December 2020

Immunization against α β and α β in Glanzmann thrombasthenia patients carrying the French Gypsy mutation.

J Thromb Haemost 2021 01 18;19(1):255-261. Epub 2020 Nov 18.

Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany.

Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal α β carrying HPA-1b epitopes. Read More

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January 2021