Hematological abnormalities in newborn infants with down syndrome

Miller, M. F.; Cosgriff, Janice M.; Opitz, John M.

doi:10.1002/ajmg.1320160207

Cited by 48 publications

(39 citation statements)

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“…[1][2][3] Blood samples were principally collected at birth from umbilical cord blood (on day 0) on days 2 and 5 (screening period for inherited metabolic disorders) and, in addition, on periods of follow-up when patients showed complete blood count abnormalities. Blood samples were immediately centrifuged and stored at À30 1C until assay for TPO levels.…”

Section: Methodsmentioning

confidence: 99%

“…[1][2][3] These include neutrophilia, thrombocytopenia, polycythemia, transient myeloproliferative disorder (TMD), neutropenia, thrombocytosis, and anemia. [1][2][3] A recent large case series study indicated thrombocytopenia below 150 Â 10 9 per liter in approximately two-third of DS infants during the first week of life, making thrombocytopenia as one of the most common hematological abnormalities. 3 Thrombopoietin (TPO), the ligand for the c-mpl receptor, is the primary regulator of thrombopoiesis and megakaryopoiesis in fetuses and neonates as well as adults.…”

Section: Introductionmentioning

confidence: 99%

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Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

et al. 2009

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Background: The pathogenesis of thrombocytopenia during the neonatal period in Down's syndrome (DS) infants remains unclear.Objective: To elucidate kinetic changes of serum thrombopoietin (TPO) level and platelet count, and their correlation in DS neonates.Study Design: Twelve DS infants (male/female: 7/5, term/late preterm: 10/2) born between 1997 and 2007 were included. Blood samples were serially collected during the neonatal period and serum TPO levels were determined in 44 sera using an enzyme-linked immunosorbent assay.Results: Thrombocytopenia <150 Â 10 9 per liter was observed in seven (58%) patients. In 12 DS patients, the median TPO value showed 2.86 fmol ml -1 on day 0, rose to 4.64 fmol ml -1 on day 2, and thereafter decreased to 4.30 fmol ml -1 on day 5, 2.40 fmol ml -1 on days 11-15, and 1.75 fmol ml -1 on days 28-30. This kinetics parallels that in historical non-DS controls. In 35 pair sample analysis from 11 patients without transient myeloproliferative disease, TPO level inversely correlated with platelet count (r ¼ À0.38, P ¼ 0.023). However, there was no significant difference in TPO concentrations between thrombocytopenic and non-thrombocytopenic DS individuals.Conclusions: This is the first study to describe the relationship between TPO level and platelet count in neonates with DS. Median TPO levels and their kinetic changes in DS neonates are comparable to those in non-DS controls. In contrast to earlier findings in several studies showing higher TPO concentrations in thrombocytopenic non-DS newborns than those in non-thrombocytopenic counterparts, the response of the TPO system to thrombocytopenia in DS during the neonatal period seems suboptimal.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

et al. 2009

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“…Single-cell suspensions of bone marrow and spleen cells were prepared and red cells lysed in ACK lysis buffer (150mM NH 4 Cl, 1mM KHCO 3 , 1M ethylenediaminetetraacetic acid). Cells were stained according to standard flow cytometric procedures using the following antibodies: biotinylated anti-Ter119 followed by streptavidin-peridinin-chlorophyll-protein complex, anti-CD19-allophycocyanin, and anti-CD3⑀-phycoerythrin (BD Pharmingen).…”

Section: Flow Cytometrymentioning

confidence: 99%

Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome

Alford

Slender

Vanes

et al. 2010

Blood

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Trisomy of human chromosome 21 (Hsa21) results in Down syndrome (DS), a disorder that affects many aspects of physiology, including hematopoiesis. DS children have greatly increased rates of acute lymphoblastic leukemia and acute megakaryoblastic leukemia (AMKL); DS newborns present with transient myelo-proliferative disorder (TMD), a preleuke-mic form of AMKL. TMD and DS-AMKL almost always carry an acquired mutation in GATA1 resulting in exclusive synthesis of a truncated protein (GATA1s), suggesting that both trisomy 21 and GATA1 mutations are required for leukemogenesis. To gain further understanding of how Hsa21 contributes to hematopoietic abnormalities , we examined the Tc1 mouse model of DS, which carries an almost complete freely segregating copy of Hsa21, and is the most complete model of DS available. We show that although Tc1 mice do not develop leukemia, they have macrocytic anemia and increased extramedullary he-matopoiesis. Introduction of GATA1s into Tc1 mice resulted in a synergistic increase in megakaryopoiesis, but did not result in leukemia or a TMD-like phenotype , demonstrating that GATA1s and tri-somy of approximately 80% of Hsa21 perturb megakaryopoiesis but are insufficient to induce leukemia. (Blood. 2010; 115(14):2928-2937) Introduction Down syndrome (DS) results from trisomy of human chromosome 21 (Hsa21, trisomy 21) and is the most common chromosomal disorder in liveborn humans. 1 Persons with DS have an increased risk of developing several hematologic defects, including macrocy-tosis, neutrophilia, thrombocytopenia, and polycythemia. 2-5 In addition, they also have an increased incidence of both acute lymphoblastic leukemia (ALL) and acute megakaryoblastic leuke-mia (AMKL) in childhood. 6 Approximately 10% of DS newborns are born with a transient myeloproliferative disorder (TMD), and, of these, 20% to 30% progress to AMKL by 4 years of age. 7,8 Both diseases are characterized by the presence of a clonal population of megakaryoblasts in the blood. However, whereas TMD is a spontaneously regressing neoplasia, AMKL is life threatening and requires chemotherapy. An important step in understanding the origins of these diseases was the discovery that almost all cases of TMD and AMKL have acquired and clonal mutations in exon 2 of the X-linked GATA1 gene, which codes for the GATA1 transcription factor. 9-14 The effect of these mutations is to prevent expression of full-length GATA1 from the normal ATG initiation codon, forcing translation to initiate at an ATG codon in exon 3, thus resulting in the synthesis of a truncated GATA1 protein termed GATA1 short (GATA1s). Examination of GATA1 mutations shows that in any one person, the mutation found in AMKL cells is the same as the mutation seen first in TMD, thus leading to the proposal that TMD is a preleukemic disease that can eventually develop into AMKL, presumably as a result of further mutations. 10,15 Interestingly, although GATA1 mutations are found in all cases of DS-AMKL, no such mutations are seen in non-DS-AMKL. 13,14 Taken together...

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“…Policitemia (MILLER & COSGRIFF, 1983), macrocitose em 65% dos casos por deficiências vitamínicas principalmente relacionada aos folatos e anemias hemolíticas (LUBIN et al, 1992), aumento da concentração intraeritrocitária da superoxidesmutase cobre-zinco (SOD1) (PANTELAKIS et al, 1970), havendo relação desta enzima com a doença de Alzheimer (ANNERÉN et al, 1986;PERCY et al, 1990). …”

Section: 5-aspectos Específicos Na Conduta Da Síndrome De Downunclassified

Curvas padrão pôndero-estatural de portadores de Síndrome de Down procedentes da região urbana da cidade de São Paulo

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Hematological abnormalities in newborn infants with down syndrome

Cited by 48 publications

References 9 publications

Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome

Curvas padrão pôndero-estatural de portadores de Síndrome de Down procedentes da região urbana da cidade de São Paulo

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