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Chapter 15 - Congenital Thrombocytopenias and Thrombocytopathies

from Section IV - Platelet Disorders

Published online by Cambridge University Press:  30 January 2021

By
Amy E. Geddis
Edited by
Pedro A. de Alarcón ,
Eric J. Werner ,
Robert D. Christensen  and
Martha C. Sola-Visner
Pedro A. de Alarcón
Affiliation:
University of Illinois College of Medicine
Eric J. Werner
Affiliation:
Children's Hospital of the King's Daughters
Robert D. Christensen
Affiliation:
University of Utah
Martha C. Sola-Visner
Affiliation:
Harvard University, Massachusetts
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Summary

Thrombocytopenia occurs in less than 1% of all newborns. However, thrombocytopenia is a common finding in the intensive-care nursery where it is present in 25–35% of admitted infants [1, 2]. See Chapters 12 and 13 for a discussion of the approach to thrombocytopenia as well as acquired causes of thrombocytopenia in newborns. This chapter will focus primarily on the diagnosis and initial management of inherited thrombocytopenia disorders that present in infancy.

Type
Chapter
Information
Neonatal Hematology
Pathogenesis, Diagnosis, and Management of Hematologic Problems
 , pp. 243 - 260
Publisher: Cambridge University Press
Print publication year: 2021

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References

Murray, NA. Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit. Acta Paediatr Suppl 2002;91(438):74–81.Google Scholar
Garcia, MG, Duenas, E, Sola, MC, et al. Epidemiologic and outcome studies of patients who received platelet transfusions in the neonatal intensive care unit. J Perinatol 2001;21(7):415–20.CrossRefGoogle ScholarPubMed
Noris, P, Pecci, A. Hereditary thrombocytopenias: A growing list of disorders. Hematology Am Soc Hematol Educ Program 2017;2017(1):385–99.Google Scholar
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(7):1511–21.CrossRefGoogle ScholarPubMed
Noris, P, Biino, G, Pecci, A, et al. Platelet diameters in inherited thrombocytopenias: Analysis of 376 patients with all known disorders. Blood 2014;124(6):e4-e10.CrossRefGoogle ScholarPubMed
Buchanan, GR, Alter, BP, Holtkamp, CA, Walsh, EG. Platelet number and function in Diamond-Blackfan anemia. Pediatrics 1981;68(2):238–41.Google Scholar
Gibson, BE, Todd, A, Roberts, I, et al. Transfusion guidelines for neonates and older children. Br J Haematol 2004;124(4):433–53.Google ScholarPubMed
Candotti, F. Clinical manifestations and pathophysiological mechanisms of the Wiskott–Aldrich syndrome. J Clin Immunol 2018;38(1):13–27.CrossRefGoogle ScholarPubMed
Bastida, JM, Del Rey, M, Revilla, N, et al. Wiskott–Aldrich syndrome in a child presenting with macrothrombocytopenia. Platelets 2017;28(4):417–20.Google Scholar
Buchbinder, D, Nugent, DJ, Fillipovich, AH. Wiskott–Aldrich syndrome: Diagnosis, current management, and emerging treatments. Appl Clin Genet 2014;7:55–66.Google Scholar
Sullivan, KE, Mullen, CA, Blaese, RM, Winkelstein, JA. A multi-institutional survey of the Wiskott–Aldrich syndrome. J Pediatr 1994;125(6 Pt 1):876–85.Google Scholar
Alekhina, O, Burstein, E, Billadeau, DD. Cellular functions of WASP family proteins at a glance. J Cell Sci 2017;130(14):2235–41.Google Scholar
Ochs, HD. Mutations of the Wiskott–Aldrich syndrome protein affect protein expression and dictate the clinical phenotypes. Immunol Res 2009; 44(1–3):84–8.CrossRefGoogle ScholarPubMed
Notarangelo, LD. In Wiskott–Aldrich syndrome, platelet count matters. Blood 2013;121(9):1484–5.Google Scholar
Crispino, JD, Horwitz, MS. GATA factor mutations in hematologic disease. Blood 2017;129(15):2103–10.CrossRefGoogle ScholarPubMed
Ochs, HD, Slichter, SJ, Harker, LA, et al. The Wiskott–Aldrich syndrome: Studies of lymphocytes, granulocytes, and platelets. Blood 1980;55(2):243–52.Google Scholar
Mathew, P, Conley, ME. Effect of intravenous gammaglobulin (IVIG) on the platelet count in patients with Wiskott–Aldrich syndrome. Pediatr Allergy Immunol 1995;6(2):91–4.CrossRefGoogle ScholarPubMed
Ozsahin, H, Cavazzana-Calvo, M, Notarangelo, LD, et al. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott–Aldrich syndrome: Collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood 2008;111(1):439–45.CrossRefGoogle ScholarPubMed
Moratto, D, Giliani, S, Bonfim, C, et al. Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott–Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980–2009: An international collaborative study. Blood 2011;118(6):1675–84.Google Scholar
Gabelli, M, Marzollo, A, Notarangelo, LD, Basso, G, Putti, MC. Eltrombopag use in a patient with Wiskott–Aldrich syndrome. Pediatr Blood Cancer 2017;64(12).Google Scholar
Gerrits, AJ, Leven, EA, Frelinger, AL, et al. Effects of eltrombopag on platelet count and platelet activation in Wiskott–Aldrich syndrome/X-linked thrombocytopenia. Blood 2015;126(11):1367–78.Google Scholar
Alexander, WS, Roberts, AW, Nicola, NA, Li, R, Metcalf, D. Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood 1996;87(6):2162–70.Google Scholar
Sitnicka, E, Lin, N, Priestley, GV, et al. The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells. Blood 1996;87(12):4998–5005.Google Scholar
Kaushansky, K. Thrombopoietin: More than a lineage-specific megakaryocyte growth factor. Stem Cells 1997;15 Suppl 1:97–103; discussion 103.CrossRefGoogle ScholarPubMed
Rose, MJ, Nicol, KK, Skeens, MA, Gross, TG, Kerlin, BA. Congenital amegakaryocytic thrombocytopenia: The diagnostic importance of combining pathology with molecular genetics. Pediatr Blood Cancer 2008;50(6):1263–5.CrossRefGoogle ScholarPubMed
Germeshausen, M, Ballmaier, M, Welte, K. Implications of mutations in hematopoietic growth factor receptor genes in congenital cytopenias. Ann N Y Acad Sci 2001;938:305–20; discussion 20–1.Google Scholar
King, S, Germeshausen, M, Strauss, G, Welte, K, Ballmaier, M. Congenital amegakaryocytic thrombocytopenia: A retrospective clinical analysis of 20 patients. Br J Haematol 2005;131(5):636–44.CrossRefGoogle ScholarPubMed
Eshuis-Peters, E, Versluys, AB, Stokman, MF, et al. Congenital amegakaryocytic thrombocytopenia Type II presenting with multiple central nervous system anomalies. Neuropediatrics 2016;47(2):128–31.Google ScholarPubMed
Martinón-Torres, N, Vázquez-Donsión, M, Loidi, L, Couselo, JM. CAMT in a female with developmental delay, facial malformations and central nervous system anomalies. Pediatr Blood Cancer 2011;56(3):452–3.Google Scholar
Bör, Ö, Turhan, AB, Yarar, C. Congenital amegakaryocytic thrombocytopenia with severe neurological findings. Blood Coagul Fibrinolysis 2016;27(8):936–9.Google Scholar
Mukai, HY, Kojima, H, Todokoro, K, et al. Serum thrombopoietin (TPO) levels in patients with amegakaryocytic thrombocytopenia are much higher than those with immune thrombocytopenic purpura. Thromb Haemost 1996;76(5):675–8.Google Scholar
Porcelijn, L, Folman, CC, Bossers, B, et al. The diagnostic value of thrombopoietin level measurements in thrombocytopenia. Thromb Haemost 1998;79(6):1101–5.CrossRefGoogle ScholarPubMed
Pecci, A, Ragab, I, Bozzi, V, et al. Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim. EMBO Mol Med 2018;10(1):63–75.CrossRefGoogle ScholarPubMed
Dasouki, MJ, Rafi, SK, Olm-Shipman, AJ, et al. Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia. Blood 2013;122(20):3440–9.Google Scholar
Greenhalgh, KL, Howell, RT, Bottani, A, et al. Thrombocytopenia-absent radius syndrome: A clinical genetic study. J Med Genet 2002;39(12):876–81.Google Scholar
Hall, JG. Thrombocytopenia and absent radius (TAR) syndrome. J Med Genet 1987;24(2):79–83.Google Scholar
Hedberg, VA, Lipton, JM. Thrombocytopenia with absent radii. A review of 100 cases. Am J Pediatr Hematol Oncol 1988;10(1):51–64.Google Scholar
Sultan, Y, Scrobohaci, ML, Rendu, F, Caen, JP. Abnormal platelet function, population, and survival-time in a boy with congenital absent radii and thrombocytopenia. Lancet 1972;2(7778):653.Google Scholar
Day, HJ, Holmsen, H. Platelet adenine nucleotide “storage pool deficiency” in thrombocytopenic absent radii syndrome. JAMA 1972;221(9):1053–4.CrossRefGoogle Scholar
Digilio, MC, Giannotti, A, Marino, B, et al. Radial aplasia and chromosome 22q11 deletion. J Med Genet 1997;34(11):942–4.Google Scholar
Klopocki, E, Schulze, H, Strauss, G, et al. Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. Am J Hum Genet 2007;80(2):232–40.Google Scholar
Albers, CA, Paul, DS, Schulze, H, et al. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nat Genet 2012;44(4):435–9, S1–2.Google Scholar
Albers, CA, Newbury-Ecob, R, Ouwehand, WH, Ghevaert, C. New insights into the genetic basis of TAR (thrombocytopenia-absent radii) syndrome. Curr Opin Genet Dev 2013;23(3):316–23.Google Scholar
Fadoo, Z, Naqvi, SM. Acute myeloid leukemia in a patient with thrombocytopenia with absent radii syndrome. J Pediatr Hematol Oncol 2002;24(2):134–5.Google Scholar
Rao, VS, Shenoi, UD, Krishnamurthy, PN. Acute myeloid leukemia in TAR syndrome. Indian J Pediatr 1997;64(4):563–5.Google Scholar
Kataoka, K, Sato, T, Yoshimi, A, et al. Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity. J Exp Med 2011;208(12):2403–16.Google Scholar
Kustikova, OS, Schwarzer, A, Stahlhut, M, et al. Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells. Leukemia 2013;27(5):1127–38.Google Scholar
Wieser, R. The oncogene and developmental regulator EVI1: Expression, biochemical properties, and biological functions. Gene 2007;396(2):346–57.Google Scholar
Germeshausen, M, Ancliff, P, Estrada, J, et al. MECOM-associated syndrome: A heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia. Blood Adv 2018;2(6):586–96.Google Scholar
Niihori, T, Ouchi-Uchiyama, M, Sasahara, Y, Kaneko, T, Hashii, Y, Irie, M, et al. Mutations in MECOM, encoding oncoprotein EVI1, cause radioulnar synostosis with amegakaryocytic thrombocytopenia. Am J Hum Genet 2015;97(6):848–54.Google Scholar
Thompson, AA, Nguyen, LT. Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation. Nat Genet 2000;26(4):397–8.Google Scholar
Walne, A, Tummala, H, Ellison, A, et al. Expanding the phenotypic and genetic spectrum of radioulnar synostosis associated hematological disease. Haematologica 2018;103(7):e284-e7.Google Scholar
Song, WJ, Sullivan, M G, Legare, RD, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet 1999;23(2):166–75.Google Scholar
Noris, P, Favier, R, Alessi, MC, et al. ANKRD26-related thrombocytopenia and myeloid malignancies. Blood 2013;122(11):1987–9.Google Scholar
Zhang, MY, Churpek, JE, Keel, SB, et al. Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nat Genet 2015;47(2):180–5.Google Scholar
Noetzli, L, Lo, RW, Lee-Sherick, AB, et al. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nat Genet 2015;47(5):535–8.Google Scholar
Latger-Cannard, V, Philippe, C, Bouquet, A, et al. Haematological spectrum and genotype-phenotype correlations in nine unrelated families with RUNX1 mutations from the French network on inherited platelet disorders. Orphanet J Rare Dis 2016;11:49.Google Scholar
Feurstein, S, Godley, LA. Germline ETV6 mutations and predisposition to hematological malignancies. Int J Hematol 2017;106(2):189–95.Google Scholar
Melazzini, F, Zaninetti, C, Balduini, CL. Bleeding is not the main clinical issue in many patients with inherited thrombocytopaenias. Haemophilia 2017;23(5):673–81.Google Scholar
Hock, H, Shimamura, A. ETV6 in hematopoiesis and leukemia predisposition. Semin Hematol 2017;54(2):98–104.CrossRefGoogle ScholarPubMed
Godley, LA, Shimamura, A. Genetic predisposition to hematologic malignancies: Management and surveillance. Blood 2017;130(4):424–32.Google Scholar
Li, R, Emsley, J. The organizing principle of the platelet glycoprotein Ib-IX-V complex. J Thromb Haemost 2013;11(4):605–14.Google Scholar
Berndt, MC, Andrews, RK. Bernard–Soulier syndrome. Haematologica 2011;96(3):355–9.CrossRefGoogle ScholarPubMed
Kunishima, S, Naoe, T, Kamiya, T, Saito, H. Novel heterozygous missense mutation in the platelet glycoprotein Ib beta gene associated with isolated giant platelet disorder. Am J Hematol 2001;68(4):249–55.Google Scholar
Ali, S, Shetty, S, Ghosh, K. A novel mutation in GP1 BA gene leads to mono-allelic Bernard–Soulier syndrome form of macrothrombocytopenia. Blood Coagul Fibrinolysis 2017;28(1):94–5.Google Scholar
Poon, MC, d’Oiron, R. Alloimmunization in congenital deficiencies of platelet surface glycoproteins: Focus on Glanzmann’s thrombasthenia and Bernard–Soulier’s syndrome. Semin Thromb Hemost 2018;44(6):604–14.Google Scholar
Ozelo, MC, Svirin, P, Larina, L. Use of recombinant factor VIIa in the management of severe bleeding episodes in patients with Bernard-Soulier syndrome. Ann Hematol 2005;84(12):816–22.Google Scholar
Hacihanefioglu, A, Tarkun, P, Gonullu, E. Use of recombinant factor VIIa in the management and prophylaxis of bleeding episodes in two patients with Bernard-Soulier syndrome. Thromb Res 2007;120(3):455–7.CrossRefGoogle ScholarPubMed
Lee, A, Poon, MC. Inherited platelet functional disorders: General principles and practical aspects of management. Transfus Apher Sci 2018;57(4):494–501.Google Scholar
Balduini, CL, Pecci, A, Savoia, A. Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. Br J Haematol 2011;154(2):161–74.Google Scholar
Seri, M, Pecci, A, Di Bari, F, et al. MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore) 2003;82(3):203–15.Google Scholar
Verver, E, Pecci, A, De Rocco, D, et al. R705 H mutation of MYH9 is associated with MYH9-related disease and not only with non-syndromic deafness DFNA17. Clin Genet 2015;88(1):85–9.Google Scholar
Pecci, A, Klersy, C, Gresele, P, et al. MYH9-related disease: A novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations. Hum Mutat 2014;35(2):236–47.Google Scholar
Harrison, P, Cramer, EM. Platelet alpha-granules. Blood Rev 1993;7(1):52–62.Google Scholar
Gunay-Aygun, M, Falik-Zaccai, TC, Vilboux, T, et al. NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet α-granules. Nat Genet 2011;43(8):732–4.Google Scholar
Albers, CA, Cvejic, A, Favier, R, et al. Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. Nat Genet 2011;43(8):735–7.Google Scholar
Kahr, WH, Hinckley, J, Li, L, et al. Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nat Genet 2011;43(8):738–40.Google Scholar
Tubman, VN, Levine, JE, Campagna, DR, et al. X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation. Blood 2007;109(8):3297–9.Google Scholar
Wijgaerts, A, Wittevrongel, C, Thys, C, et al. The transcription factor GATA1 regulates NBEAL2 expression through a long-distance enhancer. Haematologica 2017;102(4):695–706.Google Scholar
Larocca, LM, Heller, PG, Podda, G, et al. Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome. Platelets 2015;26(8):751–7.CrossRefGoogle ScholarPubMed
Nurden, AT, Nurden, P. The gray platelet syndrome: Clinical spectrum of the disease. Blood Rev 2007;21(1):21–36.Google Scholar
Khincha, PP, Savage, SA. Neonatal manifestations of inherited bone marrow failure syndromes. Semin Fetal Neonatal Med 2016;21(1):57–65.Google Scholar
Savage, SA, Walsh, MF. Myelodysplastic syndrome, acute myeloid leukemia, and cancer surveillance in Fanconi anemia. Hematol Oncol Clin North Am 2018;32(4):657–68.Google Scholar
Kutler, DI, Auerbach, AD. Fanconi anemia in Ashkenazi Jews. Fam Cancer 2004;3(3–4):241–8.Google Scholar
Callén, E, Casado, JA, Tischkowitz, MD, et al. A common founder mutation in FANCA underlies the world’s highest prevalence of Fanconi anemia in Gypsy families from Spain. Blood 2005;105(5):1946–9.Google Scholar
Feben, C, Kromberg, J, Wainwright, R, et al. Hematological consequences of a FANCG founder mutation in Black South African patients with Fanconi anemia. Blood Cells Mol Dis 2015;54(3):270–4.Google Scholar
Meetei, AR, Levitus, M, Xue, Y, et al. X-linked inheritance of Fanconi anemia complementation group B. Nat Genet 2004;36(11):1219–24.Google Scholar
Peffault de Latour, R, Soulier, J. How I treat MDS and AML in Fanconi anemia. Blood 2016;127(24):2971–9.Google Scholar
Savage, SA, Alter, BP. Dyskeratosis congenita. Hematol Oncol Clin North Am 2009;23(2):215–31.Google Scholar
Agarwal, S. Evaluation and management of hematopoietic failure in dyskeratosis congenita. Hematol Oncol Clin North Am 2018;32(4):669–85.Google Scholar
Glousker, G, Touzot, F, Revy, P, Tzfati, Y, Savage, SA. Unraveling the pathogenesis of Hoyeraal–Hreidarsson syndrome, a complex telomere biology disorder. Br J Haematol 2015;170(4):457–71.Google Scholar
Vogiatzi, P, Perdigones, N, Mason, PJ, Wilson, DB, Bessler, M. A family with Hoyeraal–Hreidarsson syndrome and four variants in two genes of the telomerase core complex. Pediatr Blood Cancer 2013;60(6):E4–6.Google Scholar
Hreidarsson, S, Kristjansson, K, Johannesson, G, Johannsson, JH. A syndrome of progressive pancytopenia with microcephaly, cerebellar hypoplasia and growth failure. Acta Paediatr Scand 1988;77(5):773–5.Google Scholar
Knight, SW, Heiss, NS, Vulliamy, TJ, et al. Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal–Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1. Br J Haematol 1999;107(2):335–9.Google Scholar
Revesz, T, Fletcher, S, al-Gazali, LI, DeBuse, P. Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: A new syndrome?J Med Genet 1992;29(9):673–5.Google Scholar
Savage, SA, Alter, BP. The role of telomere biology in bone marrow failure and other disorders. Mech Ageing Dev 2008;129(1–2):35–47.Google Scholar
Ozdemir, MA, Karakukcu, M, Kose, M, Kumandas, S, Gumus, H. The longest surviving child with Hoyeraal–Hreidarsson syndrome. Haematologica 2004;89(9):ECR38.Google Scholar
Favier, R, Douay, L, Esteva, B, et al. A novel genetic thrombocytopenia (Paris-Trousseau) associated with platelet inclusions, dysmegakaryopoiesis and chromosome deletion AT 11q23. C R Acad Sci III 1993;316(7):698–701.Google Scholar
Breton-Gorius, J, Favier, R, Guichard, J, et al. A new congenital dysmegakaryopoietic thrombocytopenia (Paris-Trousseau) associated with giant platelet alpha-granules and chromosome 11 deletion at 11q23. Blood 1995;85(7):1805–14.CrossRefGoogle ScholarPubMed
Favier, R, Akshoomoff, N, Mattson, S, Grossfeld, P. Jacobsen syndrome: Advances in our knowledge of phenotype and genotype. Am J Med Genet C Semin Med Genet 2015;169(3):239–50.Google Scholar
Grossfeld, PD, Mattina, T, Lai, Z, et al. The 11q terminal deletion disorder: A prospective study of 110 cases. Am J Med Genet A 2004;129A(1):51–61.Google Scholar
Hart, A, Melet, F, Grossfeld, P, et al. Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia. Immunity 2000;13(2):167–77.Google Scholar
Raslova, H, Komura, E, Le Couédic, JP, et al. FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia. J Clin Invest 2004;114(1):77–84.Google Scholar
Favier, R, Jondeau, K, Boutard, P, et al. Paris-Trousseau syndrome: Clinical, hematological, molecular data of ten new cases. Thromb Haemost 2003;90(5):893–7.CrossRefGoogle ScholarPubMed
Stockley, J, Morgan, NV, Bem, D, et al. Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects. Blood 2013;122(25):4090–3.Google Scholar
Saultier, P, Vidal, L, Canault, M, et al. Macrothrombocytopenia and dense granule deficiency associated with FLI1 variants: Ultrastructural and pathogenic features. Haematologica 2017;102(6):1006–16.Google Scholar
White, JG. Platelet storage pool deficiency in Jacobsen syndrome. Platelets 2007;18(7):522–7.Google Scholar
Roberts, AE, Allanson, JE, Tartaglia, M, Gelb, BD. Noonan syndrome. Lancet 2013;381(9863):333–42.Google Scholar
Tajan, M, de Rocca Serra, A, Valet, P, Edouard, T, Yart, A. SHP2 sails from physiology to pathology. Eur J Med Genet 2015;58(10):509–25.CrossRefGoogle ScholarPubMed
Nunes, P, Aguilar, S, Prado, SN, et al. Severe congenital thrombocytopaenia: First clinical manifestation of Noonan syndrome. BMJ Case Rep 2012;2012:bcr1020114940.Google Scholar
Christensen, RD, Yaish, HM, Leon, EL, Sola-Visner, MC, Agrawal, PB. A de novo T73I mutation in PTPN11 in a neonate with severe and prolonged congenital thrombocytopenia and Noonan syndrome. Neonatology 2013;104(1):1–5.Google Scholar
Artoni, A, Selicorni, A, Passamonti, SM, et al. Hemostatic abnormalities in Noonan syndrome. Pediatrics 2014;133(5):e1299–304.Google Scholar
Strullu, M, Caye, A, Lachenaud, J, et al. Juvenile myelomonocytic leukaemia and Noonan syndrome. J Med Genet 2014;51(10):689–97.Google Scholar
Kratz, CP, Franke, L, Peters, H, et al. Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes. Br J Cancer 2015;112(8):1392–7.Google Scholar
Sullivan, KE. Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Immunol Rev 2019;287(1):186–201.Google Scholar
Kato, T, Kosaka, K, Kimura, M, et al. Thrombocytopenia in patients with 22q11.2 deletion syndrome and its association with glycoprotein Ib-beta. Genet Med 2003;5(2):113–19.Google Scholar
Liang, HP, 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(6):1298–308.Google Scholar
Kunishima, S, Imai, T, Kobayashi, R, et al. Bernard-Soulier syndrome caused by a hemizygous GPIbβ mutation and 22q11.2 deletion. Pediatr Int 2013;55(4):434–7.Google Scholar
DePiero, AD, Lourie, EM, Berman, BW, et al. Recurrent immune cytopenias in two patients with DiGeorge/velocardiofacial syndrome. J Pediatr 1997;131(3):484–6.Google Scholar
Wiedmeier, SE, Henry, E, Christensen, RD. Hematological abnormalities during the first week of life among neonates with trisomy 18 and trisomy 13: Data from a multi-hospital healthcare system. Am J Med Genet A 2008;146A(3):312–20.Google Scholar
Roth, P, Sklower Brooks, S, Potaznik, D, Cooma, R, Sahdev, S. Neonatal Gaucher disease presenting as persistent thrombocytopenia. J Perinatol 2005;25(5):356–8.Google Scholar
Fairley, C, Zimran, A, Phillips, M, et al. Phenotypic heterogeneity of N370S homozygotes with type I Gaucher disease: An analysis of 798 patients from the ICGG Gaucher Registry. J Inherit Metab Dis 2008;31(6):738–44.Google Scholar
Finsterer, J. Hematological manifestations of primary mitochondrial disorders. Acta Haematol 2007;118(2):88–98.Google Scholar
Bastida, JM, Benito, R, Janusz, K, et al. Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: A brief review of hematologic abnormalities of sitosterolemia. J Thromb Haemost 2017;15(9):1859–66.Google Scholar
Bastida, JM, Giros, ML, Benito, R, et al. Sitosterolemia: Diagnosis, metabolic and hematological abnormalities, cardiovascular disease and management. Curr Med Chem 2019;26(37):6766–75.Google Scholar
Yoo, EG. Sitosterolemia: A review and update of pathophysiology, clinical spectrum, diagnosis, and management. Ann Pediatr Endocrinol Metab 2016;21(1):7–14.Google Scholar
Stewart, GW, Makris, M. Mediterranean macrothrombocytopenia and phytosterolaemia/sitosterolaemia. Haematologica 2008;93(2):e29.Google Scholar
Park, JH, Chung, IH, Kim, DH, et al. Sitosterolemia presenting with severe hypercholesterolemia and intertriginous xanthomas in a breastfed infant: Case report and brief review. J Clin Endocrinol Metab 2014;99(5):1512–18.Google Scholar
Proud, L, Ritchey, AK. Management of type 2b von Willebrand disease in the neonatal period. Pediatr Blood Cancer 2017;64(1):103–5.Google Scholar
Kruse-Jarres, R, Johnsen, JM. How I treat type 2B von Willebrand disease. Blood 2018;131(12):1292–300.Google Scholar
Othman, M. Platelet-type von Willebrand disease: A rare, often misdiagnosed and underdiagnosed bleeding disorder. Semin Thromb Hemost 2011;37(5):464–9.Google Scholar
Lotta, LA, Garagiola, I, Palla, R, Cairo, A, Peyvandi, F. ADAMTS13 mutations and polymorphisms in congenital thrombotic thrombocytopenic purpura. Hum Mutat 2010;31(1):11–19.Google Scholar
Krogh, AS, Waage, A, Quist-Paulsen, P. Congenital thrombotic thrombocytopenic purpura. Tidsskr Nor Laegeforen 2016;136(17):1452–7.Google Scholar
Taylor, A, Vendramin, C, Oosterholt, S, Della Pasqua, O, Scully, M. Pharmacokinetics of plasma infusion in congenital thrombotic thrombocytopenic purpura. J Thromb Haemost 2019; 17:88–98.CrossRefGoogle ScholarPubMed
Plautz, WE, Raval, JS, Dyer, MR, et al. ADAMTS13: Origins, applications, and prospects. Transfusion 2018;58(10):2453–62.Google Scholar
Ferrer, M, Tao, J, Iruín, G, et al. Truncation of glycoprotein (GP) IIIa (616–762) prevents complex formation with GPIIb: Novel mutation in exon 11 of GPIIIa associated with thrombasthenia. Blood 1998;92(12):4712–20.Google Scholar
Poncz, M, Rifat, S, Coller, BS, et al. Glanzmann thrombasthenia secondary to a Gly273–>Asp mutation adjacent to the first calcium-binding domain of platelet glycoprotein IIb. J Clin Invest 1994;93(1):172–9.Google Scholar
Nurden, AT. Acquired antibodies to αIIbβ3 in Glanzmann thrombasthenia: From transfusion and pregnancy to bone marrow transplants and beyond. Transfus Med Rev 2018;S0887 -7963(18)30037-3.Google Scholar
Barg, AA, Hauschner, H, Luboshitz, J, et al. From thrombasthenia to next generation thrombocytopenia: Neonatal alloimmune thrombocytopenia induced by maternal Glanzmann thrombasthenia. Pediatr Blood Cancer 2018;65(12):e27376.CrossRefGoogle ScholarPubMed
Wang, Q, Cao, L, Sheng, G, et al. Application of high-throughput sequencing in the diagnosis of inherited thrombocytopenia. Clin Appl Thromb Hemost 2018:24(9 Suppl):94S–103S.Google Scholar
Bastida, JM, Lozano, ML, Benito, R, et al. Introducing high-throughput sequencing into mainstream genetic diagnosis practice in inherited platelet disorders. Haematologica 2018;103(1):148–62.CrossRefGoogle ScholarPubMed

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