Inherited or Immunological Thrombocytopenia: The Complex Nature of Platelet Disorders in 22q11.2 Deletion Syndrome

Bartosz Urbański; Zuzanna Urbańska; Katarzyna Bąbol-Pokora; Ewelina Subocz; Wojciech Młynarski; Szymon Janczar

doi:10.1055/s-0044-1801383

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost
DOI: 10.1055/s-0044-1801383

Review Article

Inherited or Immunological Thrombocytopenia: The Complex Nature of Platelet Disorders in 22q11.2 Deletion Syndrome

Bartosz Urbański

¹Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland

,

Zuzanna Urbańska

¹Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland

²Department of Genetic Predisposition to Cancer, Medical University of Lodz, Lodz, Poland

,

Katarzyna Bąbol-Pokora

¹Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland

,

Ewelina Subocz

¹Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland

,

Wojciech Młynarski

¹Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland

,

Szymon Janczar

¹Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland

› Institutsangaben

Abstract

22q11.2 deletion syndrome (22q11.2DS) is one of the most common congenital malformation syndromes resulting from disrupted embryonic development of pharyngeal pouches. The classical triad of symptoms described by Angelo DiGeorge is frequently accompanied by hematological and immune disorders. While it is well-established that patients with 22q11.2DS have an increased risk of recurrent autoimmune cytopenias, including immune thrombocytopenia, the platelet abnormalities in this population are more complex and multifaceted. Given this issue, we conducted a comprehensive literature review on platelet disorders in 22q11.2DS using accessible databases (PubMed and Scopus). We aimed to outline previous studies limitations and most urgent challenges concerning thrombocytopenia in these patients. One characteristic finding frequently observed in 22q11.2DS is mild macrothrombocytopenia caused presumably by the loss of one GP1BB allele, encoding the element of the GPIb–IX–V complex. This structure plays a central role in thrombocyte adhesion, aggregation, and subsequent activation. Recent studies suggest that defective megakaryopoiesis and impaired vasculogenesis may strongly influence platelet and hemostasis disorders in 22q11.2DS. Furthermore, the phenotypic manifestation may be modulated by epigenetic factors and gene expression modifiers located outside the deletion region. Although the final hemorrhagic phenotype is typically mild, these patients may require more frequent transfusions following major surgical procedures. Despite the risk of thrombocytopenia and thrombocytopathy, there is a lack of large-scale research on hematological anomalies in 22q11.2DS, and the available results are often inconclusive. Given the complexity of hemostatic disorders, it is essential to establish specific recommendations for perioperative management and autoimmune cytopenias treatment within this population.

Keywords

22q11.2 deletion syndrome - DiGeorge syndrome - inherited thrombocytopenia - immune thrombocytopenia - Bernard–Soulier syndrome

Volltext

Referenzen

References
1 Blagojevic C, Heung T, Theriault M. et al. Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: a cross-sectional analysis from population-based newborn screening. CMAJ Open 2021; 9 (03) E802-E809
2 Botto LD, May K, Fernhoff PM. et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 2003; 112 (1 Pt 1): 101-107
3 McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore) 2011; 90 (01) 1-18
4 DiGeorge AM. Discussions on a new concept of the cellular base of immunology. J Pediatr 1965; 67: 907-908
5 Kelley RI, Zackai EH, Emanuel BS, Kistenmacher M, Greenberg F, Punnett HH. The association of the DiGeorge anomalad with partial monosomy of chromosome 22. J Pediatr 1982; 101 (02) 197-200
6 Driscoll DA, Salvin J, Sellinger B. et al. Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet 1993; 30 (10) 813-817
7 Burn J, Takao A, Wilson D. et al. Conotruncal anomaly face syndrome is associated with a deletion within chromosome 22q11. J Med Genet 1993; 30 (10) 822-824
8 Sergi C, Serpi M, Müller-Navia J. et al. CATCH 22 syndrome: report of 7 infants with follow-up data and review of the recent advancements in the genetic knowledge of the locus 22q11. Pathologica 1999; 91 (03) 166-172
9 Palmer LD, Butcher NJ, Boot E. et al. Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome. Am J Med Genet A 2018; 176 (04) 936-944
10 McDonald-McGinn DM, Sullivan KE, Marino B. et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers 2015; 1: 15071
11 Óskarsdóttir S, Boot E, Crowley TB. et al. Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome. Genet Med 2023; 25 (03) 100338
12 Bassett AS, McDonald-McGinn DM, Devriendt K. et al; International 22q11.2 Deletion Syndrome Consortium. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 2011; 159 (02) 332-9.e1
13 Sullivan KE. Immune biomarkers of autoimmunity in chromosome 22q11.2 deletion syndrome. J Allergy Clin Immunol Pract 2019; 7 (07) 2377-2378
14 Montin D, Marolda A, Licciardi F. et al. Immunophenotype anomalies predict the development of autoimmune cytopenia in 22q11.2 deletion syndrome. J Allergy Clin Immunol Pract 2019; 7 (07) 2369-2376
15 Lawrence S, McDonald-McGinn DM, Zackai E, Sullivan KE. Thrombocytopenia in patients with chromosome 22q11.2 deletion syndrome. J Pediatr 2003; 143 (02) 277-278
16 Crowley TB, Campbell I, Arulselvan A. et al. A case-control study of bleeding risk in children with 22q11.2 deletion syndrome undergoing cardiac surgery. Platelets 2024; 35 (01) 2290108
17 McDonald-McGinn DM, Tonnesen MK, Laufer-Cahana A. et al. Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!. Genet Med 2001; 3 (01) 23-29
18 Edelmann L, Pandita RK, Morrow BE. Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am J Hum Genet 1999; 64 (04) 1076-1086
19 Shaikh TH, Kurahashi H, Saitta SC. et al. Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum Mol Genet 2000; 9 (04) 489-501
20 Shaikh TH, O'Connor RJ, Pierpont ME. et al. Low copy repeats mediate distal chromosome 22q11.2 deletions: sequence analysis predicts breakpoint mechanisms. Genome Res 2007; 17 (04) 482-491
21 Michaelovsky E, Frisch A, Carmel M. et al. Genotype-phenotype correlation in 22q11.2 deletion syndrome. BMC Med Genet 2012; 13 (122) 122
22 Burnside RD. 22q11.21 deletion syndromes: a review of proximal, central, and distal deletions and their associated features. Cytogenet Genome Res 2015; 146 (02) 89-99
23 Gavril EC, Popescu R, Nucă I. et al. Different types of deletions created by low-copy repeats sequences location in 22q11.2 deletion syndrome: genotype-phenotype correlation. Genes (Basel) 2022; 13 (11) 2083
24 Shetty M, Srikanth A, Kadandale J, Hegde S. Pre- and postnatal diagnosis of 10p14 deletion and 22q11.2 deletion syndrome and significance of non-cardiac markers. Cytogenet Genome Res 2016; 148 (04) 249-255
25 Fernández RM, Sánchez J, García-Díaz L. et al. Interstitial 10p deletion derived from a maternal ins(16;10)(q22;p13p15.2): report of the first familial case of 10p monosomy affecting to two familial members of different generations. Am J Med Genet A 2016; 170A (05) 1268-1273
26 Papangeli I, Scambler P. The 22q11 deletion: DiGeorge and velocardiofacial syndromes and the role of TBX1. Wiley Interdiscip Rev Dev Biol 2013; 2 (03) 393-403
27 Lindsay EA, Vitelli F, Su H. et al. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 2001; 410 (6824) 97-101
28 Ogata T, Niihori T, Tanaka N. et al. TBX1 mutation identified by exome sequencing in a Japanese family with 22q11.2 deletion syndrome-like craniofacial features and hypocalcemia. PLoS One 2014; 9 (03) e91598
29 Chen M, Yang YS, Shih JC. et al. Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization. Ultrasound Obstet Gynecol 2014; 43 (04) 396-403
30 Rump P, de Leeuw N, van Essen AJ. et al. Central 22q11.2 deletions. Am J Med Genet A 2014; 164A (11) 2707-2723
31 Naqvi N, Davidson SJ, Wong D. et al. Predicting 22q11.2 deletion syndrome: a novel method using the routine full blood count. Int J Cardiol 2011; 150 (01) 50-53
32 Morrow BE, McDonald-McGinn DM, Emanuel BS, Vermeesch JR, Scambler PJ. Molecular genetics of 22q11.2 deletion syndrome. Am J Med Genet A 2018; 176 (10) 2070-2081
33 Szczawińska-Popłonyk A, Schwartzmann E, Chmara Z. et al. Chromosome 22q11.2 deletion syndrome: a comprehensive review of molecular genetics in the context of multidisciplinary clinical approach. Int J Mol Sci 2023; 24 (09) 8317
34 Liang HPH, Morel-Kopp MC, Curtin J. et al. Heterozygous loss of platelet glycoprotein (GP) Ib-V-IX variably affects platelet function in velocardiofacial syndrome (VCFS) patients. Thromb Haemost 2007; 98 (06) 1298-1308
35 Roth GJ, Yagi M, Bastian LS. The platelet glycoprotein Ib-V-IX system: regulation of gene expression. Stem Cells 1996; ;(14 Suppl 1): 188-193
36 Li R. The glycoprotein Ib-IX-V complex. In: Platelets. Academic Press;; 2019.
37 Quach ME. GPIb-IX-V and platelet clearance. Platelets 2022; 33 (06) 817-822
38 López JA, Andrews RK, Afshar-Kharghan V, Berndt MC. Bernard-Soulier syndrome. Blood 1998; 91 (12) 4397-4418
39 Berndt MC, Andrews RK. Bernard-Soulier syndrome. Haematologica 2011; 96 (03) 355-359
40 Andrews RK, Berndt MC. Bernard-Soulier syndrome: an update. Semin Thromb Hemost 2013; 39 (06) 656-662
41 Budarf ML, Konkle BA, Ludlow LB. et al. Identification of a patient with Bernard-Soulier syndrome and a deletion in the DiGeorge/velo-cardio-facial chromosomal region in 22q11.2. Hum Mol Genet 1995; 4 (04) 763-766
42 Kenny D, Morateck PA, Gill JC, Montgomery RR. The critical interaction of glycoprotein (GP) IBbeta with GPIX-a genetic cause of Bernard-Soulier syndrome. Blood 1999; 93 (09) 2968-2975
43 Kunishima S, Imai T, Kobayashi R, Kato M, Ogawa S, Saito H. Bernard-Soulier syndrome caused by a hemizygous GPIbβ mutation and 22q11.2 deletion. Pediatr Int 2013; 55 (04) 434-437
44 Ludlow LB, Schick BP, Budarf ML. et al. Identification of a mutation in a GATA binding site of the platelet glycoprotein Ibbeta promoter resulting in the Bernard-Soulier syndrome. J Biol Chem 1996; 271 (36) 22076-22080
45 Ruiz-Llobet A, Isola I, Gassiot S. et al. Platelet dysfunction in Noonan and 22q11.2 deletion syndromes in childhood. Thromb Haemost 2020; 120 (03) 457-465
46 Kato T, Kosaka K, Kimura M. et al. Thrombocytopenia in patients with 22q11.2 deletion syndrome and its association with glycoprotein Ib-β. Genet Med 2003; 5 (02) 113-119
47 Latger-Cannard V, Bensoussan D, Grégoire MJ. et al. Frequency of thrombocytopenia and large platelets correlates neither with conotruncal cardiac anomalies nor immunological features in the chromosome 22q11.2 deletion syndrome. Eur J Pediatr 2004; 163 (06) 327-328
48 Van Geet C, Devriendt K, Eyskens B, Vermylen J, Hoylaerts MF. Velocardiofacial syndrome patients with a heterozygous chromosome 22q11 deletion have giant platelets. Pediatr Res 1998; 44 (04) 607-611
49 Nurden P, Poujol C, Nurden AT. The evolution of megakaryocytes to platelets. Baillieres Clin Haematol 1997; 10 (01) 1-27
50 Tomer A, Scharf RE, McMillan R, Ruggeri ZM, Harker LA. Bernard-Soulier syndrome: quantitative characterization of megakaryocytes and platelets by flow cytometric and platelet kinetic measurements. Eur J Haematol 1994; 52 (04) 193-200
51 Zamariolli M, Auwerx C, Sadler MC. et al. The impact of 22q11.2 copy-number variants on human traits in the general population. Am J Hum Genet 2023; 110 (02) 300-313
52 Dent J, Kato K, Peng XR. et al. A prototypic platelet septin and its participation in secretion. Proc Natl Acad Sci U S A 2002; 99 (05) 3064-3069
53 Bartsch I, Sandrock K, Lanza F. et al. Deletion of human GP1BB and SEPT5 is associated with Bernard-Soulier syndrome, platelet secretion defect, polymicrogyria, and developmental delay. Thromb Haemost 2011; 106 (03) 475-483
54 Gieger C, Radhakrishnan A, Cvejic A. et al. New gene functions in megakaryopoiesis and platelet formation. Nature 2011; 480 (7376) 201-208
55 Mas S, Bernardo M, Parellada E. et al. ARVCF single marker and haplotypic association with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33 (06) 1064-1069
56 DePiero AD, Lourie EM, Berman BW, Robin NH, Zinn AB, Hostoffer RW. Recurrent immune cytopenias in two patients with DiGeorge/velocardiofacial syndrome. J Pediatr 1997; 131 (03) 484-486
57 Pachtman SL, Deng K, Nanda D. Thrombocytopenia and postpartum hemorrhage in a woman with chromosome 22q11.2 deletion syndrome. Case Rep Obstet Gynecol 2016; 2016: 2920375
58 Pinnaro CT, Henry T, Major HJ. et al. Candidate modifier genes for immune function in 22q11.2 deletion syndrome. Mol Genet Genomic Med 2020; 8 (01) e1057
59 Chen Z, Wu J, Yang C. et al. DiGeorge syndrome critical region 8 (DGCR8) protein-mediated microRNA biogenesis is essential for vascular smooth muscle cell development in mice. J Biol Chem 2012; 287 (23) 19018-19028
60 Bonati MT, Vanelli C, Sangalli D. et al. Cerebral microbleeds: a new presenting feature of chromosome 22q11.2 deletion syndrome. J Neurol Sci 2016; 368: 300-303
61 Brenner MK, Clarke S, Mahnke DK. et al. Effect of 22q11.2 deletion on bleeding and transfusion utilization in children with congenital heart disease undergoing cardiac surgery. Pediatr Res 2016; 79 (02) 318-324
62 Patel PO, Baylis AL, Hickey SE. et al. Bleeding severity and phenotype in 22q11.2 deletion syndrome-a cross-sectional investigation. J Pediatr 2021; 235: 220-225
63 Piliero LM, Sanford AN, McDonald-McGinn DM, Zackai EH, Sullivan KE. T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome. Blood 2004; 103 (03) 1020-1025
64 Yu HH, Chien YH, Lu MY. et al. Clinical and immunological defects and outcomes in patients with chromosome 22q11.2 deletion syndrome. J Clin Immunol 2022; 42 (08) 1721-1729
65 Gennery AR, Barge D, O'Sullivan JJ, Flood TJ, Abinun M, Cant AJ. Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome. Arch Dis Child 2002; 86 (06) 422-425
66 Björk AH, Óskarsdóttir S, Andersson BA, Friman V. Antibody deficiency in adults with 22q11.2 deletion syndrome. Am J Med Genet A 2012; 158A (08) 1934-1940
67 Jawad AF, McDonald-Mcginn DM, Zackai E, Sullivan KE. Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr 2001; 139 (05) 715-723
68 Janda A, Sedlacek P, Hönig M. et al. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood 2010; 116 (13) 2229-2236
69 Davies EG, Cheung M, Gilmour K. et al. Thymus transplantation for complete DiGeorge syndrome: European experience. J Allergy Clin Immunol 2017; 140 (06) 1660-1670.e16
70 Warnatz K, Voll RE. Pathogenesis of autoimmunity in common variable immunodeficiency. Front Immunol 2012; 3: 210
71 Gathmann B, Mahlaoui N, Gérard L. et al; CEREDIH, Dutch WID, European Society for Immunodeficiencies Registry Working Party. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol 2014; 134 (01) 116-126
72 Sullivan KE, McDonald-McGinn DM, Driscoll DA. et al. Juvenile rheumatoid arthritis-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome). Arthritis Rheum 1997; 40 (03) 430-436
73 Deshpande DR, Demirdag YY, Marsh RA, Sullivan KE, Orange JS. USIDNET Consortium. Relationship between severity of T cell lymphopenia and immune dysregulation in patients with DiGeorge syndrome (22q11.2 deletions and/or related TBX1 mutations): a USIDNET study. J Clin Immunol 2021; 41 (01) 29-37
74 Ricci S, Sarli WM, Lodi L. et al. Characterization of autoimmune thyroid disease in a cohort of 73 paediatric patients affected by 22q11.2 deletion syndrome: longitudinal single-centre study. Genes (Basel) 2022; 13 (09) 1552
75 Lambert MP, Arulselvan A, Schott A. et al. The 22q11.2 deletion syndrome: Cancer predisposition, platelet abnormalities and cytopenias. Am J Med Genet A 2018; 176 (10) 2121-2127
76 Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med 2017; 6 (02) 16
77 Cooper N, Ghanima W. Immune thrombocytopenia. N Engl J Med 2019; 381 (10) 945-955
78 Zheng SS, Ahmadi Z, Leung HHL. et al. Antiplatelet antibody predicts platelet desialylation and apoptosis in immune thrombocytopenia. Haematologica 2022; 107 (09) 2195-2205
79 Hernández-Nieto L, Yamazaki-Nakashimada MA, Lieberman-Hernández E, Espinosa-Padilla SE. Autoimmune thrombocytopenic purpura in partial DiGeorge syndrome: case presentation. J Pediatr Hematol Oncol 2011; 33 (06) 465-466
80 McLean-Tooke A, Spickett GP, Gennery AR. Immunodeficiency and autoimmunity in 22q11.2 deletion syndrome. Scand J Immunol 2007; 66 (01) 1-7
81 Zemble R, Luning Prak E, McDonald K, McDonald-McGinn D, Zackai E, Sullivan K. Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Immunol 2010; 136 (03) 409-418
82 Sullivan KE, McDonald-McGinn D, Zackai EH. CD4(+) CD25(+) T-cell production in healthy humans and in patients with thymic hypoplasia. Clin Diagn Lab Immunol 2002; 9 (05) 1129-1131
83 Frączkiewicz J, Sęga-Pondel D, Kazanowska B, Ussowicz M. Eltrombopag therapy in children with rare disorders associated with thrombocytopenia. J Pediatr Hematol Oncol 2020; 42 (02) 113-117
84 Akar NA, Adekile AD. Chromosome 22q11.2 deletion presenting with immune-mediated cytopenias, macrothrombocytopenia and platelet dysfunction. Med Princ Pract 2007; 16 (04) 318-320
85 Davies JK, Telfer P, Cavenagh JD, Foot N, Neat M. Autoimmune cytopenias in the 22q11.2 deletion syndrome. Clin Lab Haematol 2003; 25 (03) 195-197
86 Oliveras-Cordero HA, Rivera-Jiménez E. Recurrent Evans syndrome in a patient with 22q11.2 deletion syndrome: an uncommon hematological presentation. Cureus 2020; 12 (11) e11510
87 Kratz CP, Niehues T, Lyding S, Heusch A, Janssen G, Göbel U. Evans syndrome in a patient with chromosome 22q11.2 deletion syndrome: a case report. Pediatr Hematol Oncol 2003; 20 (02) 167-172
88 McDonald-McGinn DM, Reilly A, Wallgren-Pettersson C. et al. Malignancy in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Am J Med Genet A 2006; 140 (08) 906-909
89 Sellier C, Hwang VJ, Dandekar R. et al. Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PLoS One 2014; 9 (08) e103884
90 Bosse KR, Shukla AR, Pawel B. et al. Malignant rhabdoid tumor of the bladder and ganglioglioma in a 14 year-old male with a germline 22q11.2 deletion. Cancer Genet 2014; 207 (09) 415-419
91 Campbell IM, Crowley TB, Jobaliya C. et al. Platelet findings in 22q11.2 deletion syndrome correlate with disease manifestations but do not correlate with GPIb surface expression. Clin Genet 2023; 103 (01) 109-113
92 Zwifelhofer NMJ, Bercovitz RS, Weik LA. et al. Hemizygosity for the gene encoding glycoprotein Ibβ is not responsible for macrothrombocytopenia and bleeding in patients with 22q11 deletion syndrome. J Thromb Haemost 2019; 17 (02) 295-305
93 Souto Filho JTD, Ribeiro HAA, Fassbender IPB, Ribeiro JMMC, Ferreira Júnior WDS, Figueiredo LCS. Bernard-Soulier syndrome associated with 22q11.2 deletion and clinical features of DiGeorge/velocardiofacial syndrome. Blood Coagul Fibrinolysis 2019; 30 (08) 423-425
94 Nagoshi R, Sakamoto A, Imai T. et al. Bernard-Soulier syndrome caused by a novel GP1BB variant and 22q11.2 deletion. Int J Hematol 2024; 120 (01) 142-145
95 Sakamoto A, Uchiyama T, Futatsugi R. et al. Platelet changes and bleeding symptoms in children, adolescents, and adults with 22q11.2 deletion syndrome. Pediatr Blood Cancer 2024; 71 (11) e31292
96 Kühne T. Update on the Intercontinental Cooperative ITP Study Group (ICIS) and on the Pediatric and Adult Registry on Chronic ITP (PARC ITP). Pediatr Blood Cancer 2013; ;(60 Suppl 1): S15-S18
97 Boot E, Óskarsdóttir S, Loo JCY. et al. Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome. Genet Med 2023; 25 (03) 100344
98 Conti F, Gottardi F, Moratti M. et al. Refractory immune thrombocytopenia successfully treated with bortezomib in a child with 22q11.2 deletion syndrome, complicated by Evans syndrome and hypogammaglobulinemia. Platelets 2022; 33 (05) 801-806
99 Gu H, Mou W, Chen Z. et al. Case report: Effectiveness of sirolimus in treating partial DiGeorge Syndrome with Autoimmune Lymphoproliferative Syndrome (ALPS)-like features. Front Pediatr 2023; 10: 1014249
100 Cuker A. Light transmission aggregometry. The Hematologist 2014; . Vol. 11 (02)
101 Bolton-Maggs PHB, Chalmers EA, Collins PW. et al; UKHCDO. A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO. Br J Haematol 2006; 135 (05) 603-633
102 Rosa RFM, Rosa RCM, Dos Santos PPA, Zen PRG, Paskulin GA. Hematological abnormalities and 22q11.2 deletion syndrome. Rev Bras Hematol Hemoter 2011; 33 (02) 151-154
103 Arganbright JM, Hankey PB, Tracy M, Narayanan S, Noel-MacDonnell J, Ingram D. Tonsillectomy in children with 22q11.2 deletion syndrome. Genes (Basel) 2022; 13 (12) 2187
104 Jatana V, Gillis J, Webster BH, Adès LC. Deletion 22q11.2 syndrome–implications for the intensive care physician. Pediatr Crit Care Med 2007; 8 (05) 459-463 , quiz 464
105 Li R, Emsley J. The organizing principle of the platelet glycoprotein Ib-IX-V complex. J Thromb Haemost 2013; 11 (04) 605-614
106 Nakamura F, Pudas R, Heikkinen O. et al. The structure of the GPIb-filamin A complex. Blood 2006; 107 (05) 1925-1932