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Semin Thromb Hemost
DOI: 10.1055/s-0044-1782519
Review Article

Glanzmann Thrombasthenia 10 Years Later: Progress Made and Future Directions

Alan T. Nurden
1   Institut Hospitalo-Universitaire LIRYC, Hôpital Xavier Arnozan, Pessac, France
,
Paquita Nurden
1   Institut Hospitalo-Universitaire LIRYC, Hôpital Xavier Arnozan, Pessac, France
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Abstract

Glanzmann thrombasthenia (GT) is the most common inherited platelet disorder (IPD) with mucocutaneous bleeding and a failure of platelets to aggregate when stimulated. The molecular cause is insufficient or defective αIIbβ3, an integrin encoded by the ITGA2B and ITGB3 genes. On activation αIIbβ3 undergoes conformational changes and binds fibrinogen (Fg) and other proteins to join platelets in the aggregate. The application of next-generation sequencing (NGS) to patients with IPDs has accelerated genotyping for GT; progress accompanied by improved mutation curation. The evaluation by NGS of variants in other hemostasis and vascular genes is a major step toward understanding why bleeding varies so much between patients. The recently discovered role for glycoprotein VI in thrombus formation, through its binding to fibrin and surface-bound Fg, may offer a mechanosensitive back-up for αIIbβ3, especially at sites of inflammation. The setting up of national networks for IPDs and GT is improving patient care. Hematopoietic stem cell therapy provides a long-term cure for severe cases; however, prophylaxis by monoclonal antibodies designed to accelerate fibrin formation at injured sites in the vasculature is a promising development. Gene therapy using lentil-virus vectors remains a future option with CRISPR/Cas9 technologies offering a promising alternative route.

Keywords

Glanzmann thrombasthenia - αIIbβ3 integrin - biology - mutations - prophylaxis - gene therapy


Publication History

Article published online:
18 March 2024

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  • References

  • 1 Nurden AT, Pillois X, Wilcox DA. Glanzmann thrombasthenia: state of the art and future directions. Semin Thromb Hemost 2013; 39 (06) 642-655
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Botero JP, Lee K, Branchford BR. et al; ClinGen Platelet Disorder Variant Curation Expert Panel. Glanzmann thrombasthenia: genetic basis and clinical correlates. Haematologica 2020; 105 (04) 888-894
    CrossrefPubMedGoogle Scholar
  • 3 Nurden P, Stritt S, Favier R, Nurden AT. Inherited platelet diseases with normal platelet count: phenotypes, genotypes and diagnostic strategy. Haematologica 2021; 106 (02) 337-350
    CrossrefPubMedGoogle Scholar
  • 4 Nurden A. Profiling the genetic and molecular characteristics of Glanzmann thrombasthenia: can it guide current and future therapies?. J Blood Med 2021; 12: 581-599
    CrossrefPubMedGoogle Scholar
  • 5 Nurden AT. Should studies on Glanzmann thrombasthenia not be telling us more about cardiovascular disease and other major illnesses?. Blood Rev 2017; 31 (05) 287-299
    CrossrefPubMedGoogle Scholar
  • 6 Gresele P, Orsini S, Noris P. et al; BAT-VAL study investigators. Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: a communication from the Platelet Physiology SSC. J Thromb Haemost 2020; 18 (03) 732-739
    CrossrefPubMedGoogle Scholar
  • 7 Blaauwgeers MW, Kruip MJHA, Beckers EAM. et al. Bleeding phenotype and diagnostic characterization of patients with congenital platelet defects. Am J Hematol 2020; 95 (10) 1142-1147
    CrossrefPubMedGoogle Scholar
  • 8 Coller BS, Shattil SJ. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 2008; 112 (08) 3011-3025
    CrossrefPubMedGoogle Scholar
  • 9 Nurden AT. Molecular basis of clot retraction and its role in wound healing. Thromb Res 2023; 231: 159-169
    CrossrefPubMedGoogle Scholar
  • 10 Nurden AT, Pillois X, Fiore M. et al. Expanding the mutation spectrum affecting αIIbβ3 integrin in Glanzmann thrombasthenia: screening of the ITGA2B and ITGB3 genes in a large international cohort. Hum Mutat 2015; 36 (05) 548-561
    CrossrefPubMedGoogle Scholar
  • 11 Buitrago L, Rendon A, Liang Y. et al; ThromboGenomics Consortium. αIIbβ3 variants defined by next-generation sequencing: predicting variants likely to cause Glanzmann thrombasthenia. Proc Natl Acad Sci U S A 2015; 112 (15) E1898-E1907
    CrossrefPubMedGoogle Scholar
  • 12 Nurden AT, Pillois X. ITGA2B and ITGB3 gene mutations associated with Glanzmann thrombasthenia. Platelets 2018; 29 (01) 98-101
    CrossrefPubMedGoogle Scholar
  • 13 Xiong JP, Stehle T, Diefenbach B. et al. Crystal structure of the extracellular segment of integrin αVbeta3. Science 2001; 294 (5541): 339-345
    CrossrefPubMedGoogle Scholar
  • 14 Zhu J, Zhu J, Springer TA. Complete integrin headpiece opening in eight steps. J Cell Biol 2013; 201 (07) 1053-1068
    CrossrefPubMedGoogle Scholar
  • 15 Adair BD, Xiong J-P, Yeager M, Arnaout MA. Cryo-EM structures of full-length integrin αIIbβ3 in native lipids. Nat Commun 2023; 14 (01) 4168
    CrossrefPubMedGoogle Scholar
  • 16 Nurden AT. Acquired Glanzmann thrombasthenia: from antibodies to anti-platelet drugs. Blood Rev 2019; 36: 10-22
    CrossrefPubMedGoogle Scholar
  • 17 Nurden AT. The GPIIb-IIIa defect of platelets in Glanzmann thrombasthenia. Haematologica 2023; 108 (04) 937-938
    CrossrefPubMedGoogle Scholar
  • 18 Greinacher A, Pecci A, Kunishima S. et al. Diagnosis of inherited platelet disorders on a blood smear: a tool to facilitate worldwide diagnosis of platelet disorders. J Thromb Haemost 2017; 15 (07) 1511-1521
    CrossrefPubMedGoogle Scholar
  • 19 Mammadova-Bach E, Ollivier V, Loyau S. et al. Platelet glycoprotein VI binds to polymerized fibrin and promotes thrombin generation. Blood 2015; 126 (05) 683-691
    CrossrefPubMedGoogle Scholar
  • 20 Mangin PH, Onselaer MB, Receveur N. et al. Immobilized fibrinogen activates human platelets through glycoprotein VI. Haematologica 2018; 103 (05) 898-907
    CrossrefPubMedGoogle Scholar
  • 21 Mangin PH, Gardiner EE, Ariëns RAS, Jandrot-Perrus M. Glycoprotein VI interplay with fibrin(ogen) in thrombosis. J Thromb Haemost 2023; 21 (07) 1703-1713
    CrossrefPubMedGoogle Scholar
  • 22 Nurden AT. Clinical significance of altered collagen-receptor functioning in platelets with emphasis on glycoprotein VI. Blood Rev 2019; 38: 100592
    CrossrefPubMedGoogle Scholar
  • 23 Perrella G, Huang J, Provenzale I. et al. Nonredundant roles of platelet glycoprotein VI and integrin alphaIIbbeta3 in fibrin-mediated microthrombus formation. Arterioscler Thromb Vasc Biol 2021; 41 (02) e97-e111
    CrossrefPubMedGoogle Scholar
  • 24 Adair BD, Alonso JL, van Agthoven J. et al. Structure-guided design of pure orthosteric inhibitors of αIIbβ3 that prevent thrombosis but preserve hemostasis. Nat Commun 2020; 11 (01) 398
    CrossrefPubMedGoogle Scholar
  • 25 Buitrago L, Lefkowitz S, Bentur O, Padovan J, Coller B. Platelet binding to polymerizing fibrin is avidity driven and requires activated αIIbβ3 but not fibrin cross-linking. Blood Adv 2021; 5 (20) 3986-4002
    CrossrefPubMedGoogle Scholar
  • 26 Lickert S, Sorrentino S, Studt J-D, Medalia O, Vogel V, Schoen I. Morphometric analysis of spread platelets identifies integrin αIIbβ3-specific contractile phenotype. Sci Rep 2018; 8 (01) 5428
    CrossrefPubMedGoogle Scholar
  • 27 Nurden P, Poujol C, Winckler J, Combrié R, Caen JP, Nurden AT. A Ser752–>Pro substitution in the cytoplasmic domain of β3 in a Glanzmann thrombasthenia variant fails to prevent interactions between the alphaIIbbeta3 integrin and the platelet granule pool of fibrinogen. Br J Haematol 2002; 118 (04) 1143-1151
    CrossrefPubMedGoogle Scholar
  • 28 Lu F, Zhu L, Bromberger T. et al. Mechanism of integrin activation by talin and its cooperation with kindlin. Nat Commun 2022; 13 (01) 2362
    CrossrefPubMedGoogle Scholar
  • 29 Koukouritaki SB, Thinn AMM, Ashworth KJ. et al. A single F153Sβ3 mutation causes constitutive integrin αIIbβ3 activation in a variant form of Glanzmann thrombasthenia. Blood Adv 2023; 7 (13) 3180-3191
    CrossrefPubMedGoogle Scholar
  • 30 Litvinov RI, Weisel JW. Blood clot contraction: Mechanisms, pathophysiology, and disease. Res Pract Thromb Haemost 2022; 7 (01) 100023
    CrossrefPubMedGoogle Scholar
  • 31 Schönichen C, Montague SJ, Brouns SLN. et al. Antagonistic roles of α II bβ3 and chemokines in regulating neutrophil activation and fate on arterial thrombi under flow. Arterioscler Thromb Vasc Biol 2023; 43 (09) 1700-1712
    CrossrefPubMedGoogle Scholar
  • 32 Provenzale I, De Simone I, Gibbins JM, Heemskerk JWM, van der Meijden PEJ, Jones CI. Regulation of glycoprotein VI-dependent platelet activation and thrombus formation by heparan sulfate proteoglycan perlecan. Int J Mol Sci 2023; 24 (17) 13352
    CrossrefPubMedGoogle Scholar
  • 33 Rossi E, Pericacho M, Bachelot-Loza C. et al. Human endoglin as a potential new partner involved in platelet-endothelium interactions. Cell Mol Life Sci 2018; 75 (07) 1269-1284
    CrossrefPubMedGoogle Scholar
  • 34 Rossi E, Pericacho M, Kauskot A. et al. Soluble endoglin reduces thrombus formation and platelet aggregation via interaction with αIIbβ3 integrin. J Thromb Haemost 2023; 21 (07) 1943-1956
    CrossrefPubMedGoogle Scholar
  • 35 Takada Y, Fujita M, Takada YK. Virtual screening of protein data bank via docking simulation identified the role of integrins in growth factor signaling, the allosteric activation of integrins, and P-selectin as a new integrin ligand. Cells 2023; 12 (18) 2265
    CrossrefPubMedGoogle Scholar
  • 36 Loroch S, Trabold K, Gambaryan S. et al. Alterations of the platelet proteome in type I Glanzmann thrombasthenia caused by different homozygous delG frameshift mutations in ITGA2B. Thromb Haemost 2017; 117 (03) 556-569
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Reddy EC, Rand ML. Procoagulant phosphatidylserine-exposing platelets in vitro and in vivo . Front Cardiovasc Med 2020; 7: 15
    CrossrefPubMedGoogle Scholar
  • 38 Wang H, Bang KW, Blanchette VS, Nurden AT, Rand ML. Phosphatidylserine exposure, microparticle formation and mitochondrial depolarisation in Glanzmann thrombasthenia platelets. Thromb Haemost 2014; 111 (06) 1184-1186
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Agbani EO, van den Bosch MT, Brown E. et al. Coordinated membrane ballooning and procoagulant spreading in human platelets. Circulation 2015; 132 (15) 1414-1424
    CrossrefPubMedGoogle Scholar
  • 40 Munnix IC, Kuijpers MJ, Auger J. et al. Segregation of platelet aggregatory and procoagulant microdomains in thrombus formation: regulation by transient integrin activation. Arterioscler Thromb Vasc Biol 2007; 27 (11) 2484-2490
    CrossrefPubMedGoogle Scholar
  • 41 Agbani EO, Williams CM, Hers I, Poole AW. Membrane ballooning in aggregated platelets is synchronized and mediates a surge in microvesiculation. Sci Rep 2017; 7 (01) 2770
    CrossrefPubMedGoogle Scholar
  • 42 Abaeva AA, Canault M, Kotova YN. et al. Procoagulant platelets form an α-granule protein-covered “cap” on their surface that promotes their attachment to aggregates. J Biol Chem 2013; 288 (41) 29621-29632
    CrossrefPubMedGoogle Scholar
  • 43 Gauer JS, Duval C, Xu R-G. et al. Fibrin-glycoprotein VI interaction increases platelet procoagulant activity and impacts clot structure. J Thromb Haemost 2023; 21 (03) 667-681
    CrossrefPubMedGoogle Scholar
  • 44 Mattheij NJ, Swieringa F, Mastenbroek TG. et al. Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII. Haematologica 2016; 101 (04) 427-436
    CrossrefPubMedGoogle Scholar
  • 45 Heinzmann ACA, Karel MFA, Coenen DM. et al. Complementary roles of platelet αIIbβ3 integrin, phosphatidylserine exposure and cytoskeletal rearrangement in the release of extracellular vesicles. Atherosclerosis 2020; 310: 17-25
    CrossrefPubMedGoogle Scholar
  • 46 Zhou L, Jiang M, Shen H. et al. Clinical and molecular insights into Glanzmann's thrombasthenia in China. Clin Genet 2018; 94 (02) 213-220
    CrossrefPubMedGoogle Scholar
  • 47 Koker MY, Sarper N, Albayrak C. et al. New αIIbβ3 variants in 28 Turkish Glanzmann patients; structural hypothesis for complex activation by residues variations in I-EGF domains. Platelets 2022; 33 (04) 551-561
    CrossrefPubMedGoogle Scholar
  • 48 Siddiqi MYJ, Boeckelmann D, Naz A. et al. Glanzmann thrombasthenia in Pakistani patients: Identification of 7 novel pathogenic variants in the fibrinogen receptor αIIbβ3. Cells 2023; 12 (02) 213
    CrossrefPubMedGoogle Scholar
  • 49 Simeoni I, Stephens JC, Hu F. et al. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders. Blood 2016; 127 (23) 2791-2803
    CrossrefPubMedGoogle Scholar
  • 50 Downes K, Megy K, Duarte D. et al; NIHR BioResource. Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders. Blood 2019; 134 (23) 2082-2091
    CrossrefPubMedGoogle Scholar
  • 51 Zhang J, Tang J, Li G. et al. SINE-VNTR-Alu retrotransposon insertion as a novel mutational event underlying Glanzmann thrombasthenia. J Thromb Haemost 2023; 21 (12) 3597-3607
    CrossrefPubMedGoogle Scholar
  • 52 Owaidah T, Saleh M, Baz B. et al. Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients. NPJ Genom Med 2019; 4: 4
    CrossrefPubMedGoogle Scholar
  • 53 Yang EJ, Shim YJ, Kim HS. et al; On Behalf Of The Benign Hematology Committee Of The Korean Pediatric Hematology Oncology Group Kphog. 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; 12 (05) 693
    CrossrefPubMedGoogle Scholar
  • 54 Megy K, Downes K, Morel-Kopp M-C. et al. GoldVariants, a resource for sharing rare genetic variants detected in bleeding, thrombotic, and platelet disorders: communication from the ISTH SSC Subcommittee on Genomics in Thrombosis and Hemostasis. J Thromb Haemost 2021; 19 (10) 2612-2617
    CrossrefPubMedGoogle Scholar
  • 55 Ross JE, Zhang BM, Lee K. et al. Specifications of the variant curation guidelines for ITGA2B/ITGB3: ClinGen platelet disorder variant curation panel. Blood Adv 2021; 5 (02) 414-431
    CrossrefPubMedGoogle Scholar
  • 56 Kosaka Y, Jacob S, Di Paolo J. et al. Multiplexed functional assessment of Glanzmann thrombasthenia variants (Abstract 1204). Paper presented at: The Annual Meeting of the American Society of Hematology Meeting, December 9, 2023, San Diego, United States
    PubMedGoogle Scholar
  • 57 Bunimov N, Fuller N, Hayward CP. Genetic loci associated with platelet traits and platelet disorders. Semin Thromb Hemost 2013; 39 (03) 291-305
    Article in Thieme ConnectPubMedGoogle Scholar
  • 58 Keramati AR, Chen M-H, Rodriguez BAT. et al; NHLBI Trans-Omics for Precision (TOPMed) Consortium. Genome sequencing unveils a regulatory landscape of platelet reactivity. Nat Commun 2021; 12 (01) 3626
    CrossrefPubMedGoogle Scholar
  • 59 Ghouse J, Tragante V, Ahlberg G. et al. Genome-wide meta-analysis identifies 93 risk loci and enables risk prediction equivalent to monogenic forms of venous thromboembolism. Nat Genet 2023; 55 (03) 399-409
    CrossrefPubMedGoogle Scholar
  • 60 Stefanucci L, Collins J, Sims MC. et al. The effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders in 140 214 UK Biobank participants. Blood 2023; 142 (24) 2055-2068
    CrossrefPubMedGoogle Scholar
  • 61 Guillet B, Bayart S, Pillois X, Nurden P, Caen JP, Nurden AT. A Glanzmann thrombasthenia family associated with a TUBB1-related macrothrombocytopenia. J Thromb Haemost 2019; 17 (12) 2211-2215
    CrossrefPubMedGoogle Scholar
  • 62 Danckwardt S, Trégouët DA, Castoldi E. Post-transcriptional control of haemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders. Cardiovasc Res 2023; 119 (08) 1624-1640
    CrossrefPubMedGoogle Scholar
  • 63 Cimmino G, Conte S, Palumbo D. et al. The novel role of noncoding RNAs in modulating platelet function: implications in activation and aggregation. Int J Mol Sci 2023; 24 (08) 7650
    CrossrefPubMedGoogle Scholar
  • 64 Garcia A, Dunoyer-Geindre S, Nolli S, Strassel C, Reny JL, Fontana P. miR-204-5p and platelet function regulation: insight into a mechanism mediated by CDC42 and GPIIbIIIa. Thromb Haemost 2021; 121 (09) 1206-1219
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Aslan JE, Tormoen GW, Loren CP, Pang J, McCarty OJ. S6K1 and mTOR regulate Rac1-driven platelet activation and aggregation. Blood 2011; 118 (11) 3129-3136
    CrossrefPubMedGoogle Scholar
  • 66 Nurden AT, Nurden P. Inherited thrombocytopenias: history, advances and perspectives. Haematologica 2020; 105 (08) 2004-2019
    CrossrefPubMedGoogle Scholar
  • 67 Bury L, Falcinelli E, Chiasserini D, Springer TA, Italiano Jr JE, Gresele P. Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia. Haematologica 2016; 101 (01) 46-56
    CrossrefPubMedGoogle Scholar
  • 68 Kim C, Lau TL, Ulmer TS, Ginsberg MH. Interactions of platelet integrin alphaIIb and β3 transmembrane domains in mammalian cell membranes and their role in integrin activation. Blood 2009; 113 (19) 4747-4753
    CrossrefPubMedGoogle Scholar
  • 69 Kashiwagi H, Kunishima S, Kiyomizu K. et al. Demonstration of novel gain-of-function mutations of αIIbβ3: association with macrothrombocytopenia and glanzmann thrombasthenia-like phenotype. Mol Genet Genomic Med 2013; 1 (02) 77-86
    CrossrefPubMedGoogle Scholar
  • 70 Akuta K, Kiyomizu K, Kashiwagi H. et al. Knock-in mice bearing constitutively active αIIb(R990W) mutation develop macrothrombocytopenia with severe platelet dysfunction. J Thromb Haemost 2020; 18 (02) 497-509
    CrossrefPubMedGoogle Scholar
  • 71 Favier M, Bordet JC, Favier R. et al. Mutations of the integrin αIIb/β3 intracytoplasmic salt bridge cause macrothrombocytopenia and enlarged platelet α-granules. Am J Hematol 2018; 93 (02) 195-204
    CrossrefPubMedGoogle Scholar
  • 72 Morais S, Oliveira J, Lau C. et al. αIIbβ3 variants in ten families with autosomal dominant macrothrombocytopenia: expanding the mutational and clinical spectrum. PLoS One 2020; 15 (12) e0235136
    CrossrefPubMedGoogle Scholar
  • 73 Nurden P, Bordet JC, Pillois X, Nurden AT. An intracytoplasmic β3 Leu718 deletion in a patient with a novel platelet phenotype. Blood Adv 2017; 1 (08) 494-499
    CrossrefPubMedGoogle Scholar
  • 74 Miyashita N, Onozawa M, Hayasaka K. et al. A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction. Ann Hematol 2018; 97 (04) 629-640
    CrossrefPubMedGoogle Scholar
  • 75 Zhang H, Zhu DS, Zhu J. Family-wide analysis of integrin structures predicted by AlphaFold2. Comput Struct Biotechnol J 2023; 21: 4497-4507
    CrossrefPubMedGoogle Scholar
  • 76 Di Minno G, Zotz RB, d'Oiron R, Bindslev N, Di Minno MN, Poon M-C. Glanzmann Thrombasthenia Registry Investigators. The international, prospective Glanzmann Thrombasthenia Registry: treatment modalities and outcomes of non-surgical bleeding episodes in patients with Glanzmann thrombasthenia. Haematologica 2015; 100 (08) 1031-1037
    PubMedGoogle Scholar
  • 77 Poon MC, d'Oiron R, Zotz RB, Bindslev N, Di Minno MN, Di Minno G. Glanzmann Thrombasthenia Registry Investigators. The international, prospective Glanzmann Thrombasthenia Registry: treatment and outcomes in surgical intervention. Haematologica 2015; 100 (08) 1038-1044
    PubMedGoogle Scholar
  • 78 Orsini S, Noris P, Bury L. et al; European Hematology Association - Scientific Working Group (EHA-SWG) on thrombocytopenias and platelet function disorders. Bleeding risk of surgery and its prevention in patients with inherited platelet disorders. Haematologica 2017; 102 (07) 1192-1203
    CrossrefPubMedGoogle Scholar
  • 79 Al-Battat S, Rand ML, Bouskill V. et al. Glanzmann thrombasthenia platelets compete with transfused platelets, reducing the haemostatic impact of platelet transfusions. Br J Haematol 2018; 181 (03) 410-413
    CrossrefPubMedGoogle Scholar
  • 80 Lee RH, Piatt R, Dhenge A. et al. Impaired hemostatic activity of healthy transfused platelets in inherited and acquired platelet disorders: Mechanisms and implications. Sci Transl Med 2019; 11 (522) aay0203
    CrossrefPubMedGoogle Scholar
  • 81 Fiore M, d'Oiron R, Pillois X, Alessi MC. Anti-αIIbβ3 immunization in Glanzmann thrombasthenia: review of literature and treatment recommendations. Br J Haematol 2018; 181 (02) 173-182
    CrossrefPubMedGoogle Scholar
  • 82 Poon M-C, D'Oiron R, Baby S, Zotz RB, Di Minno G. The Glanzmann Thrombasthenia Registry: safety of platelet therapy in patients with Glanzmann thrombasthenia and changes in alloimmunization status. Haematologica 2023; 108 (10) 2855-2858
    CrossrefPubMedGoogle Scholar
  • 83 Wihadmadyatami H, Röder L, Berghöfer H. et al. Immunisation against αIIbβ3 and αvβ3 in a type 1 variant of Glanzmann's thrombasthenia caused by a missense mutation Gly540Asp on β3. Thromb Haemost 2016; 116 (02) 262-271
    PubMedGoogle Scholar
  • 84 Santoso S, Wihadmadyatami H, Bakchoul T. et al. Antiendothelial alphavbeta3 antibodies are a major cause of intracranial bleeding in fetal/neonatal alloimmune thrombocytopenia. Arterioscler Thromb Vasc Biol 2016; 36 (08) 1517-1524
    CrossrefPubMedGoogle Scholar
  • 85 Fiore M, Sentilhes L, d'Oiron R. How I manage pregnancy in women with Glanzmann thrombasthenia. Blood 2022; 139 (17) 2632-2641
    CrossrefPubMedGoogle Scholar
  • 86 Poon M-C. The use of recombinant activated Factor VII in patients with Glanzmann's thrombasthenia. Thromb Haemost 2021; 121 (03) 332-340
    Article in Thieme ConnectPubMedGoogle Scholar
  • 87 Rajpurkar M, Chitlur M, Recht M, Cooper DL. Use of recombinant activated factor VII in patients with Glanzmann's thrombasthenia: a review of the literature. Haemophilia 2014; 20 (04) 464-471
    CrossrefPubMedGoogle Scholar
  • 88 Chitlur M, Rajpurkar M, Recht M. et al. Recognition and management of platelet-refractory bleeding in patients with Glanzmann's thrombasthenia and other severe platelet function disorders. Int J Gen Med 2017; 10: 95-99
    CrossrefPubMedGoogle Scholar
  • 89 Sattler L, Wimmer J, Herb A, Gerout AC, Feugeas O, Desprez D. Apixaban for treatment of venous thromboembolism in an obese patient with Glanzmann thrombasthenia. Res Pract Thromb Haemost 2023; 7 (04) 100183
    CrossrefPubMedGoogle Scholar
  • 90 Constantinescu-Bercu A, Grassi L, Frontini M, Salles-Crawley II, Woollard K, Crawley JT. Activated αIIbβ3 on platelets mediates flow-dependent NETosis via SLC44A2. eLife 2020; 9: e53353
    CrossrefPubMedGoogle Scholar
  • 91 Ji Y, Temprano-Sagrera G, Holle LA. et al; CHARGE Consortium Hemostasis Working Group, INVENT Consortium. Antithrombin, protein C, and protein S: genome and transcriptome-wide association studies identify 7 novel loci regulating plasma levels. Arterioscler Thromb Vasc Biol 2023; 43 (07) e254-e269
    PubMedGoogle Scholar
  • 92 Yeaman MR. Platelets: at the nexus of antimicrobial defence. Nat Rev Microbiol 2014; 12 (06) 426-437
    CrossrefPubMedGoogle Scholar
  • 93 Maouia A, Rebetz J, Kapur R, Semple JW. The immune nature of platelets revisited. Transfus Med Rev 2020; 34 (04) 209-220
    CrossrefPubMedGoogle Scholar
  • 94 Sattler L, Feugeas O, Hager C, Grunebaum L, Desprez D. COVID-19 in a pediatric patient with Glanzmann thrombasthenia. Pediatr Blood Cancer 2020; 67 (10) e28662
    CrossrefPubMedGoogle Scholar
  • 95 Rapkiewicz AV, Mai X, Carsons SE. et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series. EClinicalMedicine 2020; 24: 100434
    CrossrefPubMedGoogle Scholar
  • 96 Gaertner F, Ahmad Z, Rosenberger G. et al. Migrating platelets are mechano-scavengers that collect and bundle bacteria. Cell 2017; 171 (06) 1368-1382.e23
    CrossrefPubMedGoogle Scholar
  • 97 Mandel J, Casari M, Stepanyan M, Martyanov A, Deppermann C. Beyond hemostasis: Platelet Innate immune interactions and thromboinflammation. Int J Mol Sci 2022; 23 (07) 3868
    CrossrefPubMedGoogle Scholar
  • 98 Kaiser R, Escaig R, Kranich J. et al. Procoagulant platelet sentinels prevent inflammatory bleeding through GPIIBIIIA and GPVI. Blood 2022; 140 (02) 121-139
    CrossrefPubMedGoogle Scholar
  • 99 Kaiser R, Escaig R, Nicolai L. Hemostasis without clot formation: how platelets guard the vasculature in inflammation, infection, and malignancy. Blood 2023; 142 (17) 1413-1425
    CrossrefPubMedGoogle Scholar
  • 100 Uhl B, Haring F, Slotta-Huspenina J. et al. Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature. Front Immunol 2023; 14: 1078005
    CrossrefPubMedGoogle Scholar
  • 101 Desprez D, Sattler L, Wimmer J, Feugeas O, Gerout AC, Chamouard P. Efficacy of octreotide in the treatment of gastrointestinal angiodysplasia in a patient with Glanzmann thrombasthenia. Transfus Med 2022; 32 (06) 519-521
    CrossrefPubMedGoogle Scholar
  • 102 Paciullo F, Fierro T, Calcinaro F, Zucca Giucca G, Gresele P, Bury L. Long-term treatment with thalidomide for severe recurrent hemorrhage from intestinal angiodysplasia in Glanzmann Thrombasthenia. Platelets 2021; 32 (02) 288-291
    CrossrefPubMedGoogle Scholar
  • 103 Saladino A, Gonzalez ML, Chuliber FA, Serra MM. Glanzmann's thrombasthenia associated with gastrointestinal angiodysplasias successfully treated with bevacizumab. Blood Coagul Fibrinolysis 2023; 34 (08) 545-548
    CrossrefPubMedGoogle Scholar
  • 104 Wilcox DA. Megakaryocyte- and megakaryocyte precursor-related gene therapies. Blood 2016; 127 (10) 1260-1268
    CrossrefPubMedGoogle Scholar
  • 105 Li D, Peng J, Li T, Liu Y, Chen M, Shi X. Itgb3-integrin-deficient mice may not be a sufficient model for patients with Glanzmann thrombasthenia. Mol Med Rep 2021; 23 (06) 449
    CrossrefPubMedGoogle Scholar
  • 106 Fang J, Jensen ES, Boudreaux MK. et al. Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs. Proc Natl Acad Sci U S A 2011; 108 (23) 9583-9588
    CrossrefPubMedGoogle Scholar
  • 107 Sullivan SK, Mills JA, Koukouritaki SB. et al. High-level transgene expression in induced pluripotent stem cell-derived megakaryocytes: correction of Glanzmann thrombasthenia. Blood 2014; 123 (05) 753-757
    CrossrefPubMedGoogle Scholar
  • 108 Hu L, Du L, Zhao Y. et al. Modeling Glanzmann thrombasthenia using patient specific iPSCs and restoring platelet aggregation function by CD41 overexpression. Stem Cell Res (Amst) 2017; 20: 14-20
    CrossrefPubMedGoogle Scholar
  • 109 Zhang N, Zhi H, Curtis BR. et al. CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes. Blood 2016; 127 (06) 675-680
    CrossrefPubMedGoogle Scholar
  • 110 Fiore M, Giraudet J-S, Alessi M-C. et al. Emergency management of patients with Glanzmann thrombasthenia: consensus recommendations from the French reference center for inherited platelet disorders. Orphanet J Rare Dis 2023; 18 (01) 171
    CrossrefPubMedGoogle Scholar
  • 111 Nugent D, Acharya SS, Baumann KJ. et al. Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities for ultra-rare inherited bleeding disorders. Expert Rev Hematol 2023; 16 (sup1): 55-70
    CrossrefPubMedGoogle Scholar
  • 112 Tarawah A, Albagshi MH, Owaidah T. Management of Glanzmann's thrombasthenia – Guidelines based on an expert panel consensus from gulf cooperatic council countries. J Appl Haematol 2019; 10 (01) 1-9
    CrossrefPubMedGoogle Scholar
  • 113 Duncan A, Kellum A, Peltier S, Cooper DL, Saad H. Disease burden in patients with Glanzmann's thrombasthenia: Perspectives from the Glanzmann's thrombasthenia patient/caregiver questionnaire. J Blood Med 2020; 11: 289-295
    PubMedGoogle Scholar
  • 114 Gandhi PS, Zivkovic M, Ostergaard H. et al. A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders. Nat Cardiovasc Res 2024; 3: 166-185
    CrossrefPubMedGoogle Scholar
  • 115 Sivapalaratnam S, Austin S, Lorch U. et al. A phase1/2, First-in-human, study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of HMB-001 in participants with Glanzmann thrombasthenia (abstract 1225). Paper presented at: The Annual Meeting of the American Society of Hematology Meeting, December 9, 2023, San Diego, United States
    PubMedGoogle Scholar
  • 116 Schmoker AM, Perez Pearson LM, Cruz C. et al. Defining the TLT-1 interactome from resting and activated human platelets. J Proteomics 2020; 215: 103638
    CrossrefPubMedGoogle Scholar
  • 117 Romasko EJ, Devkota B, Biswas S. et al. Utility and limitations of exome sequencing in the molecular diagnosis of pediatric inherited platelet disorders. Am J Hematol 2018; 93 (01) 8-16
    CrossrefPubMedGoogle Scholar