Article
Cell Biology
M. Y. Koker, N. Sarper, C. Albayrak, B. Zulfikar, E. Zengin, B. Saraymen, D. Albayrak, B. Koc, H. Avcilar, M. Karakukcu, C. Chenet, F. Bianchi, A. G. de Brevern, R. Petermann, V Jallu
Summary: This study reported platelet phenotypes and allelic variations in 28 Turkish GT patients, and investigated the effects of different variants on alpha IIb beta 3 expression using transfected cell lines. New alleles were described, and it was suggested that some variations might be new causes of GT.
Article
Pediatrics
Zhengrong Wang, Yuqing Xu, Yixi Sun, Shuang Wang, Minyue Dong
Summary: In this study, a 7-year-old Chinese boy with Glanzmann thrombasthenia (GT) was described. The diagnosis was based on typical clinical manifestations, absence of blood clot retraction, and reduced expression of CD41 and CD61 on platelets. A homozygous silent variant c.1431C > T (p. G477=) of the ITGB3 gene was identified and predicted to affect splicing. Further analysis revealed a deletion of 95 base pairs, frameshift, and creation of a premature stop codon in exon 10 of ITGB3 (p. G477Afs*30). The identified variant was confirmed to be the cause of Glanzmann thrombasthenia.
FRONTIERS IN PEDIATRICS
(2023)
Article
Biochemical Research Methods
Lancong Liu, Wenfeng Ding, Lili He, Yi Yang, Fuyi Guan, Xinlin Sun, Yan Peng, Xue Chen, Wenhao Zhao, Yu Xiao, Pei Luo
Summary: We synthesized a novel peptide, WK001, by modifying the RGD structure to combine with scutellarin. Experimental and docking evidence showed that WK001 provides immediate and potent platelet inhibition, surpassing the inhibition of eptifibatide and scutellarin in platelet aggregation. In vivo studies demonstrated that WK001 administered intravenously prevents thrombus formation and attenuates myocardial fibrosis progression. Therefore, WK001 has the potential to be developed as an antiplatelet drug for thrombosis-associated diseases, such as stroke and myocardial infarction.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Hematology
Sevasti B. Koukouritaki, Aye Myat M. Thinn, Katrina J. Ashworth, Juan Fang, Haley S. Slater, Lily M. Du, Huong Thi Thu Nguyen, Xavier Pillois, Alan T. Nurden, Christopher J. Ng, Jorge Di Paola, Jieqing Zhu, David A. Wilcox
Summary: This report identifies a novel variant form of Glanzmann thrombasthenia, exhibiting only mild bleeding. Platelets cannot aggregate ex vivo with physiological agonists, but display moderate ex vivo platelet adhesion and aggregation. Reduced expression of & alpha;IIb & beta;3 on quiescent platelets and activation-dependent antibodies suggest an intrinsic activation phenotype. Genetic analysis reveals a single F153S & beta;3 substitution, suggesting its important role in integrin structure/function. Disruption of F153 & beta;3 significantly alters normal integrin/platelet function, but reduced expression of & alpha;IIbS153 & beta;3 may be compensated by hyperactive conformation promoting viable hemostasis.
Article
Hematology
Man-Chiu Poon
Summary: The study summarized evidence from three different sources demonstrating the efficacy and safety of rFVIIa in patients with GT without refractoriness or antibodies to platelets, supporting the label extension of rFVIIa as an alternative treatment when platelets are unavailable.
THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Biochemistry & Molecular Biology
Finola Priyadharshini Chandrasekaran, Adarsh Vishal, Udita Arora, S. Udhaya Kumar, C. Priya Doss George, Everette Jacob Remington Nelson
Summary: Mutations in the alpha IIb beta-propeller domain disrupt heterodimerization and intracellular trafficking of alpha IIb beta 3 complexes, leading to Glanzmann thrombasthenia. The study aims to understand the conformational changes caused by three specific beta-propeller mutations (G128S, S287L, and G357S) and reveals differences in protein transport and stability among them.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Hematology
Jianmin Liu, Fan Lu, Sujay Subbayya Ithychanda, Marcin Apostol, Mitali Das, Gauravi Deshpande, Edward F. Plow, Jun Qin
Summary: This study reveals that filamin associates with both inactive and active forms of alpha IIb ss 3, promoting platelet spreading. Furthermore, the study demonstrates that filamin undergoes spatiotemporal rearrangement upon alpha IIb ss 3 activation, binding to the alpha IIb cytoplasmic tail alone. This novel alpha IIb CT-filamin-actin linkage plays a crucial role in integrin outside-in signaling.
Article
Hematology
Balkrishna Padate, Dia Mansukhani, Farah Jijina, Shanaz Khodaiji
Summary: Qualitative platelet function defects can be congenital or acquired, with Glanzmann thrombasthenia being a genetic disorder. Besides genetic factors, acquired disorders can also lead to platelet function abnormalities, often associated with autoimmune diseases, hematologic malignancies, and infections. Accurate diagnosis and appropriate management are crucial in preventing catastrophic bleeding.
JOURNAL OF HEMATOPATHOLOGY
(2021)
Article
Oncology
Dongya Li, Jie Peng, Tiantian Li, Yichen Liu, Min Chen, Xiaofeng Shi
Summary: Itgb3(-/-) mice exhibit unique characteristics that differ from those of GT patients and thus cannot fully simulate patients with GT.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Daniel Gao, Caroline W. Sun, Angela B. Woodley, Jing-fei Dong
Summary: Clot retraction, which requires the functional platelet alpha(IIb)beta(3) integrin, is an important measure of platelet function and can be used to detect functional changes in platelets. Platelet counts and the surface density of the integrin alpha(IIb)beta(3) affect clot retraction.
Article
Biochemistry & Molecular Biology
Lili Donner, Tobias Feige, Carolin Freiburg, Laura Mara Toska, Andreas S. Reichert, Madhumita Chatterjee, Margitta Elvers
Summary: Alzheimer's disease is characterized by an accumulation of amyloid beta (Aβ) peptides in the brain and mitochondrial dysfunction. Platelet activation is enhanced in AD, leading to pathological manifestations, and anti-platelet therapy has shown promising results in reducing these effects. Mitochondrial dysfunction plays a significant role in platelet-mediated Aβ aggregate formation, suggesting it as a potential target for limiting pathological manifestations in AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Roger E. G. Schutgens, Rolf T. Urbanus
Summary: A patient with Glanzmann Thrombasthenia developed recurrent venous thrombosis associated with a JAK2 positive myeloproliferative neoplasm. The platelet aIIb beta III integrin appears to have no role in venous thrombosis, and dabigatran was successfully used in this case. Other potential mechanisms of venous thrombosis are discussed.
CLINICAL CASE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Dan Shu, Ying Zhu, Meng Lu, Ao-Di He, Jiang-Bin Chen, Ding-Song Ye, Yue Liu, Xiang-Bin Zeng, Rong Ma, Zhang-Yin Ming
Summary: Sanguinarine demonstrates antiplatelet activity by inhibiting thrombus formation and platelet activation through multiple molecular mechanisms. This indicates its potential clinical value in treating cardiovascular diseases involving excessive platelet activation.
Article
Hematology
XueHong Li, Jing Xu, ZhenJiang Li, Yuan Song, Yan Fei, GuiLin Yang, AiPing Tang
Summary: This study aimed to elucidate the molecular characteristics of a Chinese family with Glanzmann's thrombasthenia (GT), identifying a novel ITGB3 gene mutation in the pedigree. Heterozygous mutations were found in multiple family members, while the specific mutation identified in the proband was not present in public genetic databases.
ACTA HAEMATOLOGICA
(2022)
Article
Integrative & Complementary Medicine
Bo-Ra Jeon, Muhammad Irfan, Seung Eun Lee, Jeong Hoon Lee, Man Hee Rhee
Summary: The study found that Rumex acetosella extract has inhibitory effects on platelet activity and can exert its effects by modulating signaling pathways. This suggests that Rumex acetosella may have a protective role in the development of cardiovascular diseases.
CHINESE JOURNAL OF INTEGRATIVE MEDICINE
(2022)