Infantile pyknocytosis, a neonatal hemolytic anemia with Heinz bodies: A cohort study.

Infantile pyknocytosis (IP) is a rare, probably misestimated, cause of non-immune neonatal hemolytic anemia evolving in two phases: an initial phase with severe jaundice, followed by a second phase with hemolytic anemia, which may require neonatal intensive care. The diagnosis of IP is based on the transient presence on blood smear of hyperdense, contracted, and/or spiculated red blood cells (pyknocytes), associated with the spontaneous resolution of clinico-biological features and the exclusion of other causes. If the etiology remains undetermined, some contributing factors, such as oxidative stress, have been proposed. We report the description of 16 patients with IP aiming at clarifying the circumstances associated with the development of this acquired disorder. In the acute phase, the mean hemoglobin nadir and pyknocyte count were 7.8 g/dL and 11%, respectively, and strikingly, Heinz bodies were evident in 50% of the newborns, but in 100% after prolonged incubation (4 hours). A high proportion of Mediterranean or African ancestry was noted in newborns, as well as a significant number of peripartum events, such as respiratory distress. If the etiology of IP is certainly multifactorial, our series reinforces the role of oxidative stress, which may, at least in part, find origin in desaturation episodes in newborns.

Infantile Pyknocytosis in a Premature Dichorionic Diamniotic Twin.

Infantile pyknocytosis is a rare and self-limiting cause of hemolytic anemia in neonates. It can result in severe anemia and hyperbilirubinemia. The pathogenesis is unknown: a genetic origin has been discussed; however, based on the current literature it is not clear which genetic mutations should be considered. We present a case of a premature twin, in whom genetic screening was performed. Genetic mutations in 46 genes associated with hereditary hemolytic anemia and dyserythropoietic anemia were tested. No mutations were found. In infantile pyknocytosis, a genetic defect in these genes is unlikely.

The singular case of multiple chorangioma syndrome in an IVF pregnancy. Analysis of the case and review of literature.

The redacted classification of placental lesions identifies in the group of fetal-stromal vascular lesions a subgroup called villous capillary lesions. The causes of villous capillary lesions appear to involve excessive angiogenesis. These conditions include chorangiosis, chorangiomatosis, chorangioma and a rare variant of the latter called multiple chorangioma syndrome where multiple chorangiomas, ranging from very small early precursor lesions to typical macroscopic chorangioma, occupy up to 80% of the total placental parenchyma. We present the first case of multiple chorangioma syndrome in an oncologic patient who obtained the pregnancy by egg donation, comparing the clinical case with ones available in literature. Fifteen cases have been previously published in literature but only 11 were eligible for the present review. We compared clinical characteristics and fetal outcomes with our clinical case, to highlight similarities and differences useful for a better understanding of this rare and partially unknown disease. Multiple chorangioma syndrome is a rare villous capillary lesion associated with poor fetal condition. All cases analyzed have been conceived naturally and our case is the first described in an IVF pregnancy. We believe that in our case the advanced maternal age, the method of conception and the previous chemo-therapeutic treatments might have played an important role in determining the manifestation of this rare placental condition. However, there is not appropriate literature supporting our consideration and, for future studies, it could be reasonable investigate the incidence of this condition, or even the incidence of all cluster of villous capillary lesions, in oncologic and IVF patients.

Severe neonatal anemia increases intestinal permeability by disrupting epithelial adherens junctions.

Anemia is a frequent diagnosis in critically ill infants, but the clinical implications of severe anemia in these patients remain unclear. In this study, we examined preweaned mice to investigate the effects of severe anemia during early infancy on gut mucosal permeability. C57BL/6 mice were subjected to timed phlebotomy between postnatal days (P) 2-10 to induce severe anemia (hematocrits 20%-24%), and intestinal permeability was tracked longitudinally between P10 and P20 as intestine-to-plasma translocation of enteral macromolecules and bacterial translocation. Epithelial junctions were evaluated by electron microscopy, polymerase chain reactions, immunohistochemistry, and/or enzyme immunoassays on intestinal tissues, Caco-2 intestinal epithelial-like cells, and colonic organoids. Preweaned mouse pups showed an age-related susceptibility to severe anemia, with increased intestinal permeability to enteral macromolecules (dextran, ovalbumin, ß-lactoglobulin) and luminal bacteria. Electron micrographs showed increased paracellular permeability and ultrastructural abnormalities of the adherens junctions. These findings were explained by the loss of E-cadherin in epithelial cells, which was caused by destabilization of the E-cadherin (Cdh1) mRNA because of microRNA let-7e-5p binding to the 3'-untranslated region. Severe anemia resulted in a disproportionate and persistent increase in intestinal permeability in preweaned mice because of the disruption of epithelial adherens junctions. These changes are mediated via microRNA let-7e-mediated depletion of Cdh1 mRNA.NEW & NOTEWORTHY This research article shows that newborn infants with severe anemia show an age-related susceptibility to developing increased intestinal permeability to ingested macromolecules. This abnormal permeability develops because of abnormalities in intestinal epithelial junctions caused by a deficiency of the molecule E-cadherin in epithelial cells. The deficiency of E-cadherin is caused by destabilization of its mRNA precursor because of increased expression and binding of another molecule, the microRNA let-7e-5p, to the E-cadherin mRNA.

A family affair-Severe fetal and neonatal hemolytic anemia due to novel alpha-spectrin mutations in two siblings.

Hereditary spherocytosis (HS) is the most common cause of inherited, nonimmune hemolytic anemia. When inherited in an autosomal dominant fashion, the anemia is typically mild. However, severe, transfusion-dependent anemia is seen in autosomal recessive HS, which is often associated with deficient or absent red blood cell membrane protein alpha-spectrin. We report a 26-year-old para one who was referred to our center at 28 weeks' gestation due to concerns for fetal anemia. Evaluation revealed elevated peak systolic velocity in the middle cerebral artery by Doppler scan and fetal cardiomegaly. Fetal hematocrit obtained by sampling the umbilical vein was 9% confirming severe fetal anemia. Fetal peripheral smear was consistent with hereditary spherocytosis. Genetic analysis of both parents confirmed heterozygosity for the SPTA1 variants (pathogenic variant c.4180del (p.C1394Afs*25), and a variant of uncertain significance, c.1677G>T (p.G449G)) detected by a hemolytic anemia panel in the patient's first child. It is important to consider genetic causes of anemia in patients presenting with severe nonimmune fetal anemia, including autosomal recessive HS. We present a case of autosomal recessive HS with a novel pathogenic variant in the SPTA1 gene which resulted in significant impact on prenatal management.

SIFD as a novel cause of severe fetal hydrops and neonatal anaemia with iron loading and marked extramedullary haemopoiesis.

SIFD describes a heritable, syndromic condition characterised principally by sideroblastic anaemia (SA) with immunodeficiency, fevers and developmental delay, arising in mutations within the TRNT1 gene. Other clinical manifestations of SIFD include cardiomyopathy, seizures, sensorineural hearing loss, renal dysfunction, metabolic abnormalities, hepatosplenomegaly and retinitis pigmentosa.Presentation of SIFD is variable but typically in early childhood with SA or with fever. In this report, we extend the described SIFD phenotype. We describe a kindred in which the index case presented with fetal hydrops, and early neonatal death, and the second child had severe anaemia at delivery. Both cases had prominent extramedullary erythropoiesis and numerous circulating nucleated red blood cells.

Redness discordance in monochorionic twin placentas: Correlation with clinical and placental findings.

INTRODUCTION/OBJECTIVES: Recent studies suggest redness (color) discordance of the placental basal plate may be a marker for twin anemia-polycythemia sequence (TAPS), a recently described complication of diamniotic-monochorionic twinning characterized by marked intertwin hemoglobin (Hb) discordance in the absence of oligohydramnios-polyhydramnios. In this study, we determined the clinicoplacental and choriovascular correlates of basal plate color discordance in monochorionic twin placentas, and assessed its value as postnatal indicator of TAPS. METHODS: We performed a clinicoplacental analysis of 100 consecutive non-TTTS diamniotic-monochorionic twin placentas with available photographic documentation of the basal plate. Basal plate redness was quantified by computer-assisted analysis of digital images and expressed as intertwin color difference ratio (CDR). RESULTS: The CDR ranged between 1.00 and 3.58 (median CDR: 1.14; 90th %ile: 1.98). Compared to twins with low CDR (N = 90), twins with high CDR (≥2.0; N = 10) had significantly higher hemoglobin difference (11.25 g/dL versus 2.55 g/dL) and significantly fewer and smaller artery-to-artery (AA) and artery-to-vein (AV) anastomoses. Apgar scores and birth weights were equivalent in both groups. Among the 10 twin sets with high CDR, six (60%) qualified as TAPS, as defined by intertwin Hb difference >8 g/dL and absent or very small AA and AV anastomoses. Conversely, 6 of 8 (75%) twin sets with TAPS had a CDR ≥ 2.0. CONCLUSION: Intertwin CDR correlates with intertwin hemoglobin difference and chorionic angioarchitecture. A CDR value ≥ 2.0 (the 90%ile value for CDR derived from the present cohort) has high specificity (96%), but relatively low positive predictive value (60%) as indicator of TAPS, as currently defined.

KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.

We describe a case of severe neonatal anemia with kernicterus caused by compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1-null human. The phenotype of severe nonspherocytic hemolytic anemia, jaundice, hepatosplenomegaly, and marked erythroblastosis is more severe than that present in congenital dyserythropoietic anemia type IV as a result of dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found that human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell-cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control, and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis.

Association between red blood cell transfusion and bronchopulmonary dysplasia in preterm infants.

Anemia and the need for transfusion of packed red blood cells (PRBCs) are common in preterm infants. PRBC transfusion increases the oxygen carrying capacity of hemoglobin and may result in higher rates of organ dysfunction. To determine whether PRBC transfusion in preterm infants is associated with an increased incidence of bronchopulmonary dysplasia (BPD), this retrospective study was performed on neonates with birth weights ≤ 1,500 g or gestational age ≤ 32 weeks admitted from August, 2008 to November, 2013. Infants who received PRBC transfusion before the diagnosis of BPD and those who did not receive PRBC transfusion or received PRBC transfusion after diagnosis of BPD were compared for incidence of BPD and other morbidities. Of 231 preterm infants, 137 received PRBC transfusion before BPD was diagnosed (group 1) and 94 did not (group 2). The incidence of BPD was significantly higher in group 1 than in group 2 (37.2% vs. 2.1%, P < 0.00001). After adjusting for potential risk factors, the adjusted odds ratio for BPD was 9.80 (95% confidence interval, 1.70-56.36; P = 0.01). This study demonstrated an association between PRBC transfusion and BPD in preterm infants. A cautious approach to PRBC transfusion in these infants is warranted.

Anemia de células falciformes: Guía de manejo pediátrico / Sickle cell disease: pediatric management guide

La anemia de células falciformes o drepanocítica es una enfermedad común en la edad pediátrica, con alta mortalidad en menores de 5 años de edad. Cuando un niño hereda esta condición de sus padres quienes son portadores, los glóbulos rojos sufren un cambio de forma o “falciformación”, alterando el flujo de sangre y provocando enfermedad, dolor y daño de órganos. Es necesario el despistaje universal a todos los recién nacidos, para identificar los afectados e iniciar tempranamente su cuidado y educación a los padres para prevenir ytratar las complicaciones, permitiéndoles tener una mejor calidad de vida. Se presentan unas guías y opciones terapéuticas para laprevención y el manejo de las complicaciones

Sickle cell disease (SCD) is a common condition in childhood with a high mortality rate, especially under 5 years of age. When children inherit SCD from their carrier parents, the red blood cells form an abnormal sickled shape. As a result, blood does not flow well, causingdisease, pain and organ damage. Universal newborn screening is necessary to identify and treat early those affected babies, thus preventing complications and allowing them to have a healthier life. Here is a set of guidelines and treatment options to prevent and manage sickle cell related complications

[Neonatal Pearson syndrome. two case studies]. / Le syndrome de Pearson : à propos de 2 observations à révélation néonatale.

Among the etiologies of anemia in the newborn, those related to mitochondrial cytopathies are rare. Pearson syndrome is mostly diagnosed during infancy and characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells and exocrine pancreatic dysfunction. We describe two diagnosed cases of Pearson syndrome in the early neonatal period caused by severe macrocytic aregenerative anemia. Bone marrow aspiration revealed sideroblastic anemia and vacuolization of erythroblastic precursors. The diagnosis was confirmed by genetic analysis revealing a deletion in the mitochondrial DNA. These two newborns received monthly transfusions. Five other newborns suffering from Pearson syndrome with various clinical symptoms were found in literature. Pearson syndrome, rarely diagnosed in newborns, should be suspected in the presence of macrocytic aregenerative anemia and requires a bone marrow aspirate followed by a genetic analysis from a blood sample.

Postmortem diagnosis of Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a rare etiology for congenital anemia, but this diagnosis should be considered when aregenerative hypoplastic anemia occurs in infancy. A term infant girl received a red blood cell transfusion at birth for neonatal anemia (hemoglobin 75 g/L) initially attributed to abruptio placentae. There were no additional investigations. Hemoglobin gradually decreased during the first 4 weeks of life, leading to severe anemia and death despite transfusions. A postmortem diagnosis of DBA was made by extraction of DNA collected on blood filter paper showing a deletion in RPS19 gene. Neonatal anemias should be carefully investigated and close follow-up should be performed during the first months of life, even if there is an obvious hemorrhagic etiology.

New variant of congenital dyserythropoietic anemia with trilineage myelodysplasia.

We report the case of a male infant with a variant of congenital dyserythropoietic anemia (CDA), who developed severe hyperbilirubinemia on the day of birth, subsequent severe anemia, and hyperferritinemia. Bone marrow and laboratory examinations revealed features of CDA including trilineage myelodysplasia and erythroblasts with a binucleated nuclear morphology and ineffective erythropoiesis. The CDA in this patient was assumed to be a new variant type because of: the lack of internuclear chromatin bridges in the erythroblasts with abnormal nuclear morphology; a negative acid serum test; the presence of erythrocyte antigen I, and the effect of splenectomy. Trilineage myelodysplasia in CDA is not known. An abnormality in the stem cells was suggested to be the cause of CDA in this case.

Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity.

To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity, we randomly assigned 19 anemic preterm infants (birth weight 988 +/- 227 gm; gestational age 27.6 +/- 1.2 weeks; age 41 +/- 15 days; all values mean +/- SD) to receive either transfusion or subcutaneously administered erythropoietin (200 units/kg every other day for 10 doses). In the 10 erythropoietin recipients, corrected reticulocyte counts increased from 2% +/- 1% to 7% +/- 2% (p less than 0.001) and hematocrits increased from 27% +/- 2% to 30% +/- 4% (p less than 0.05). In the nine infants who underwent transfusion, reticulocyte counts did not increase, but hematocrits increased from 28% +/- 4% to 41% +/- 2% after initial transfusion (p less than 0.001) and had decreased to 34% +/- 5% by day 20. Signs attributed to anemia (tachycardia, apnea with bradycardia, and poor weight gain) declined in both the erythropoietin recipients and those who underwent transfusion. However, five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions. Marrow aspiration performed after 7 to 10 days of treatment showed that infants receiving erythropoietin had greater percentages of erythropoietic precursors (p less than 0.01), greater concentrations of mature erythroid progenitors (p less than 0.001), and higher cycling rates of erythroid progenitors (p less than 0.001). The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group, resulting in an inverse myeloid/erythroid ratio (0.5:1 vs 6.2:1; p less than 0.001). After 20 days, absolute blood neutrophil counts were lower in the erythropoietin recipients (1.8 +/- 0.9 x 10(3) cells/microliters) than in the infants who underwent transfusion (3.9 +/- 1.9 x 10(3) cells/microliters; p less than 0.05). Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia; the significance of the relative neutropenia remains to be determined. We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity.