Infantile Pyknocytosis Research Articles

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 7.8g/dL and 11%, respectively, and strikingly, Heinz bodies were evident in 50% of the newborns, but in 100% after prolonged incubation (4hours). 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 with marked hemolytic anemia

A 38-day-old Japanese infant was referred to our facility with a 4-day history of jaundice. He was born at term by normal vaginal delivery, had not received phototherapy, was on mixed feeding, and had no abnormalities detected at a checkup 6 days previously. On examination, he was jaundiced but had no other physical abnormalities. Laboratory tests were as follows: hemoglobin, 4.9 g/dL (normal range: 10.2–12.7 g/dL, severe anemia); reticulocytes, 17.8%, 2.7 × 105 cells/μL (2.12–3.47%, 0.5–0.7 × 105 cells/μL, reticulocytosis); mean corpuscular volume, 96 fL (86.5–92.1 fL); mean corpuscular hemoglobin concentration, 34.3 g/dL (34.0–35.5 g/dL); serum haptoglobin, <10 mg/dL (0–222 mg/dL); total bilirubin, 10.4 mg/dL (0.1–1.9 mg/dL); direct bilirubin, 0.9 mg/dL (0–0.6 mg/dL); and lactate dehydrogenase, 433 IU/L (158–373 IU/L).

Infantile pyknocytosis: A rare cause of newborn hemolytic anemia two case reports

Infantile pyknocytosis (IP) is a rare cause of neonatal hemolytic disease. The exact etiology of this entity remains unclear. It is characterized by prolonged jaundice and transient hemolytic anemia, combined with increased proportion of pyknocytes in peripheral blood smear. Diagnosis is exclusively based on the detection of a higher proportion of pyknocytes in peripheral blood smear. IP is a self-restricted disease. In this case series study we present the diagnostic approach, therapeutic intervention and outcome of two neonates, presented with unconjugated hyperbilirubinemia and major hemolysis, the 17th and 21st day of life respectively, treated with phototherapy and excellent outcome. Despite the low incidence of this entity, IP should be included in the differential diagnosis in case of prolonged neonatal jaundice not well explained by other common of hemolytic anemia.

PS1202 DIFFERENTIAL DIAGNOSIS OF CONGENITAL HEMOLYTIC ANEMIA OF NEONATES AND INFANTS IN JAPAN

Background:As a reference center, we analyze erythrocyte membranes, enzymes, and hemoglobin for congenital hemolytic anemia (CHA) in cases that are not diagnosed using ordinary laboratory examinations, and we introduce genetic testing using a hemolytic anemia‐related gene panel. We analyzed 136 cases from 2016 to 2017, including 36 patients under 1 year of age and 100 patients aged 1 year and over. Consequently, a definitive diagnosis was obtained for 84% of patients aged 1 and over but for only 72% of patients under 1 year of age.Aims:We aimed to summarize the final diagnosis for hemolytic anemia in patients less than 1 year of age analyzed over 3 years from 2016 to 2018 and discuss the common clinical features and laboratory data of undiagnosed cases.Methods:We analyzed 58 infantile CHA casesusing the following laboratory tests: flow‐cytometric osmotic fragility (FCM‐OF) test, eosin 5’‐maleimide binding test, assay of 15 red blood cell (RBC) enzymes, reduced glutathione content, and isopropanol stability test for unstable hemoglobinopathy. For the cases with a difficult diagnosis, genetic analysis with target‐captured sequencing (TCS) using a gene panel of 74 genes related to CHA was carried out.Results:Among 58 infants with CHA, we diagnosed 30 cases (52%); there were 18 cases of hereditary spherocytosis (HS), 2 cases of hereditary elliptocytosis (HE), 1 case of hereditary pyropoikilocytosis, 4 cases of erythro‐enzymopathies, and 2 cases of unstable hemoglobinopathies. Among the 28 undiagnosed cases, 14 showed an elevated percentage of residual RBCs in the FCM‐OF test. These cases also showed abnormal RBC morphologies such as target cells, stomatocytes, and/or pyknocytes. We performed TCS for 4 of the 14 cases, but none harbored mutations such as PIEZO1 or KCNN4. Of the 7 cases, which could be followed up to at the age of one year, all recovered from CHA within a year.Summary/Conclusion:Mild hemolytic anemia accompanied by stomatocytes and/or target cells is a typical clinical feature of dehydrated hereditary stomatocytosis (DHSt) in adults. We previously showed that FCM‐OF clearly discriminated DHSt from HS or HE (Utsugisawa et al., Blood 2017;130:929). In this study, approximately half of the infants with undiagnosed CHA showed similar RBC morphology and higher osmotic resistance with no causative gene mutations. We noticed that clinical pictures of these infants resembled the description of infantile pyknocytosis (IP), which is a transient neonatal hemolytic anemia with the characteristic RBC morphology. As IP cases follow a relatively benign clinical course, we propose that FCM‐OF may be used as a biomarker for the tentative diagnosis of IP.

PS1203 HEREDITARY SPHEROCYTOSIS: SCREENING AND DIAGNOSTIC APPROACH IN A BELGIAN LABORATORY

Background: As a reference center, we analyze erythrocyte membranes, enzymes, and hemoglobin for congenital hemolytic anemia (CHA) in cases that are not diagnosed using ordinary laboratory examinations, and we introduce genetic testing using a hemolytic anemia-related gene panel. We analyzed 136 cases from 2016 to 2017, including 36 patients under 1 year of age and 100 patients aged 1 year and over. Consequently, a definitive diagnosis was obtained for 84% of patients aged 1 and over but for only 72% of patients under 1 year of age. Aims: We aimed to summarize the final diagnosis for hemolytic anemia in patients less than 1 year of age analyzed over 3 years from 2016 to 2018 and discuss the common clinical features and laboratory data of undiagnosed cases. Methods: We analyzed 58 infantile CHA casesusing the following laboratory tests: flow-cytometric osmotic fragility (FCM-OF) test, eosin 5’-maleimide binding test, assay of 15 red blood cell (RBC) enzymes, reduced glutathione content, and isopropanol stability test for unstable hemoglobinopathy. For the cases with a difficult diagnosis, genetic analysis with target-captured sequencing (TCS) using a gene panel of 74 genes related to CHA was carried out. Results: Among 58 infants with CHA, we diagnosed 30 cases (52%); there were 18 cases of hereditary spherocytosis (HS), 2 cases of hereditary elliptocytosis (HE), 1 case of hereditary pyropoikilocytosis, 4 cases of erythro-enzymopathies, and 2 cases of unstable hemoglobinopathies. Among the 28 undiagnosed cases, 14 showed an elevated percentage of residual RBCs in the FCM-OF test. These cases also showed abnormal RBC morphologies such as target cells, stomatocytes, and/or pyknocytes. We performed TCS for 4 of the 14 cases, but none harbored mutations such as PIEZO1 or KCNN4. Of the 7 cases, which could be followed up to at the age of one year, all recovered from CHA within a year. Summary/Conclusion: Mild hemolytic anemia accompanied by stomatocytes and/or target cells is a typical clinical feature of dehydrated hereditary stomatocytosis (DHSt) in adults. We previously showed that FCM-OF clearly discriminated DHSt from HS or HE (Utsugisawa et al., Blood 2017;130:929). In this study, approximately half of the infants with undiagnosed CHA showed similar RBC morphology and higher osmotic resistance with no causative gene mutations. We noticed that clinical pictures of these infants resembled the description of infantile pyknocytosis (IP), which is a transient neonatal hemolytic anemia with the characteristic RBC morphology. As IP cases follow a relatively benign clinical course, we propose that FCM-OF may be used as a biomarker for the tentative diagnosis of IP.

Pyknocytose infantile : une cause d’anémie hémolytique néonatale. Érythropoïétine recombinante, une alternative à la transfusion ?

Infantile pyknocytosis is a neonatal hemolytic disorder which causes anemia and icterus and is characterized by the presence of an increased number of distorted red blood cells called pyknocytes. Resolution spontaneously occurs in the first semester of life. It has been generally described as a rare entity, with an occasional family history. We report seven cases of infantile pyknocytosis observed in our hospital in 3 years. Most of the infants presented with hemolytic icterus and profound anemia that was reaching its peak by the 3rd week of life. Three neonates received one to three red blood cell transfusions, according to former recommendations. However, the following four received a treatment with recombinant erythropoietin administered subcutaneously. Only one of these four cases required a transfusion. All of them were free of hematological disease 2-3 months after completion of treatment. Infantile pyknocytosis is a recognized cause of neonatal hemolytic anemia, which requires careful examination of red cell morphology on a peripheral blood smear. The cause of this transient disorder remains unknown. Our observations show that recombinant erythropoietin therapy is effective in treating infantile pyknocytosis and increases the reticulocyte response, thus improving the hemoglobin level.

Early postnatal diagnosis of hereditary spherocytosis by combining light microscopy, acidified glycerol lysis test and eosin-5'-maleimide binding assay.

Exact diagnosis of hereditary spherocytosis (HS) is widely considered unreliable around birth. However, early postnatal diagnosis at the beginning of congenital hemolysis may be essential for managing neonatal anemia and hemolytic icterus, identifying those at high risk for severe hyperbilirubinemia, irreversible kernicterus, or sudden need for red cell transfusion. We analyzed 37 blood samples from neonates or infants up to six weeks of life that had been collected in-house or shipped to our laboratory due to suspected red cell membrane disorder. By combining assessment of red cell morphology, acidified glycerol lysis test (AGLT), and eosin-5'-maleimide (EMA) binding assay, we were able to clearly exclude HS in 22 and confirm HS in 10 patients, of which one had undergone red cell transfusion prior to blood sampling. Assessment of red cell morphology and normal test results allowed diagnosis of infantile pyknocytosis or Heinz body anemia in three neonates. Re-evaluation of five patients with inconsistent results of AGLT and EMA binding led to confirmation of HS in two cases. Automated analysis of hematologic parameters revealed elevated proportion of hyperdense cells to be a highly significant indicator for HS in neonatal infants. We showed that assessment of red cell morphology in combination with AGLT and EMA binding assay is a reliable basis for confirming or rejecting suspected diagnosis of HS even in neonates. Our data underline the necessity for blood sampling and laboratory exploration in suspected red cell membrane or enzyme defects at the earliest occasion.

Infantile Pyknocytosis: An Under-Recognized Form of Neonatal Hemolytic Anemia?

Infantile pyknocytosis (IP) is an under-recognized hematological entity of newborns that can cause a severe neonatal hemolytic anemia. A careful, prompt, and accurate peripheral blood smear examination is essential to establish the diagnosis. Here we describe the clinical features and histological parameters of 1 case of IP. Spontaneous resolution usually occurs by 4 to 6 months, but red blood cell transfusion may be needed if the anemia is severe.

La pyknocytose infantile : une anémie néonatale mal connue à propos de 5 cas

Infantile pyknocytosis (IP) is a rare hematological entity of newborns. It is a form of hemolytic anemia with unusual red cell morphology: the red blood cells are distorted, irregular, and small with many projections. Spontaneous resolution usually occurs by 4-6months of age. We describe the clinical features and biological parameters of 5 cases of IP. The first symptoms were always early jaundice, which required phototherapy. Anemia was severe in all babies and red blood cell transfusion was needed. IP is a rare cause of neonatal anemia whose diagnosis is based on a careful peripheral blood smear examination. In our study, anemia was severe and required red blood cell transfusion. Ethnic specificity and familial occurrence are reported in our experience.

Erythropoietin treatment can prevent blood transfusion in infantile pyknocytosis

Erythropoietin treatment can prevent blood transfusion in infantile pyknocytosis

Familial infantile pyknocytosis in association with pulmonary hypertension

Infantile pyknocytosis is a rare condition characterized by transient neonatal hemolytic anemia associated with increased pyknocyte count on blood smear. We describe three siblings with infantile pyknocytosis, born to consanguineous parents. The first and third siblings had neonatal hemolytic anemia that resolved spontaneously at 6 months. The second sibling presented at 11 days with severe hemolytic anemia along with pulmonary hypertension. He died at 39 days from sepsis. The findings support a possible autosomal recessive inheritance. We hypothesize that pulmonary hypertension may be secondary to or aggravated by neonatal hemolysis.

Infantile pyknocytosis: a cause of haemolytic anaemia of the newborn

This study defined the incidence, clinical and haematological characteristics of infantile pyknocytosis in a monocentric retrospective study of 149 blood samples referred for unexplained neonatal haemolytic anaemia. Pyknocytosis was diagnosed in 14 patients (9.4%). All patients had neonatal jaundice and severe anaemia (mean nadir haemoglobin: 6.8 g/dl) at a mean age of 21 d. The percentage of pyknocytes was 4-23%. Packed red blood cell transfusions were needed in 11 of 14 patients. Haemoglobin levels reached normal values within a mean time of 4 months. Infantile pyknocytosis is an unusual cause of neonatal haemolytic anaemia, which requires careful examination of blood smears.

Infantile pyknocytosis: a cause of intrauterine haemolysis in 2 siblings.

Infantile pyknocytosis, a rare cause of intrauterine haemolysis and potential perinatal death, is described and the relevant literature reviewed. Treatment consists of preterm delivery with exchange transfusion as necessary to control the haemolytic process and hyperbilirubinaemia.

Infantile pyknocytosis: A cause of intrauterine haemolysis in two siblings

Pyknocytosis is a rare cause of haemolytic anaemia in utero and in the neonatal period. Two unusually severe cases of infantile pyknocytosis in 2 siblings are described. The first sibling, a male infant, was delivered prematurely at 37 wk. At birth the child had moderately severe jaundice and hepatosplenomegaly. The cord blood film showed marked pyknocytosis with numerous nucleated red cells. During the first 6 h of life the child developed clinical and laboratory evidence of disseminated intravascular coagulation. An attempt was made to do exchange transfusion but the child died 6 h after birth. The autopsy showed evidence of marked extramedullar erythropoiesis consistent with intrauterine haemolytic anaemia. The second infant of the parents was closely monitored during pregnancy as the history in the first infant had suggested severe intrauterine haemolysis. Amniocentesis was performed at 33 wk and 35 wk of gestation and showed an increase in bilirubin suggestive of a moderately severely affected infant. The baby was delivered by caesarean section at 35 wk and at birth showed evidence of haemolytic anaemia. Cord blood:haemoglobin 11.2 g/dl; PCV 36%; MCV 104 μ m 3 ; MCHC 32.7%; MCH 34 pg; reticulocyte count 21.3%; 126 nucleated red cells per 100 white cells; WCC 12,900 × 10 3 and platelet count 273 × 10 3 . Peripheral blood showed marked pyknocytosis very similar to the blood film of the first infant. The investigations to exclude enzyme deficiencies such as G6-PD, P-K. and glutathione reductase were normal. β -lipoproteins were also normal. No Heinz bodies were detected. To control hyperbilirubinaemia, the baby required 3 exchange transfusions. Despite exchange transfusions pyknocytosis persisted with evidence of recurrence of anaemia. The pyknocytosis and haemolytic anaemia persisted until 4 mth of age. A previous report suggested that the erythrocyte abnormality may have resulted from a plasma factor present in the affected infants. However, in our patient red cell morphology was not corrected by incubating the red cells with fresh plasma, nor were normal erythrocytes affected when incubated with the infant’s plasma. It would appear therefore that the erythrocyte abnormality is a transient but intrinsic abnormality of red cell membrane.

RHEOLOGIC PARAMETERS IN DISEASE STATES OF INFANCY AND CHILDHOOD

Alterations in rheologic parameters may play an important role in many disease states. Hyperviscosity secondary to polycythemia, leukocytosis or abnormal blood proteins may contribute to the pathogenesis of serious symptomatology due to sludging of blood flow. Decreased erythrocyte (RBC) deformability may contribute both to hyperviscosity and to the premature removal of sclerocytic erythrocytes by the spleen.In a study of 68 patients during 1970-73 the following rheologic abnormalities were found.(1) Hyperviscosity due to polycythemia in: neonatal hyperviscosity, cyanotic heart disease and cystic fibrosis.(2) Decreased RBC deformability alone in: respiratory distress syndrome, infants of diabetic mothers, immune hemolysis, infantile pyknocytosis, advanced liver disease, nephrosls, renal failure and intrinsic RBC defects.(3) Hyperviscosity of whole blood due to both polycythemia and decreased RBC deformability in: neonatal hyperviscosity syndrome, infants of diabetic mothers and cystic fibrosis.(4) Hyperviscosity due to increased leukocytes in: the myeloproliferative syndrome of trisomy 21 and acute leukemia.(5) Hyperviscosity due to parenteral protein concentrates in: hemophilia after intensive transfusion.Investigation into the role of altered rheology in these conditions may increase our knowledge of disease mechanisms and associated laboratory and clinical findings.

Fetal erythrocyte deformability—physiologic, rheologic, and clinical considerations

Investigation of fetal red blood cell (RBC) deformability by filtration and viscosimetry has shown that the fetal RBC varies significantly from the adult. Cord blood from 15 newborns was compared with 14 adults. Triple washed RBC's in Eagle's albumin buffer with a hematocrit of 10 ± .5% were passed through a polycarbonate filter with a 3 μ × 13.5 μ cylindrical pore under constant pressure. Flow velocity (μl/sec) was calculated. Cell suspensions were modified by adjusting temperature, pH and pO2 prior to filtration. Mean corpuscular volume (MCV), reticulocyte count and fibrinogen were measured. Viscosity of whole blood, 40% cells in autologous plasma and 80% washed cells was deterined. Filterability, as a measure of RBC deformation, was markedly decreased in newborn samples. Mean flow velocity was 2.2 μl/sec Lowered pH or pO2 in the prefiltrate resulted in significantly decreased filterability in newborn samples only. Filterability correlated poorly with MCV. Two infants with polycythemic hyperviscosity syndrome showed increased viscosity of whole blood, 80% cell suspension and markedly decreased filterability. An infant with pyknocytosis and markedly decreased filterability. An infant with pyknocytosis showed decreased filterability and elevated viscosity of an 80% suspension compared to normal newborns. Decreased deformability of the fetal RBC may be related to shortened newborn RBC survival involving diminished ability to pass through the splenic microcirculation. The decreased fetal RBC deformability which can be aggravated by acidosis and hypoxia contributes to hyperviscosity in newborns with high hematocrits. The decrease in red cell survival and anemia in infantile pyknocytosis may also be related to altered RBC deformability.

The causes and differential diagnosis of microangiopathic haemolytic anaemia in children

Microangiopathic haemolytic anaemia (MHA) is generally easily differentiated from other causes of poikilocytosis, but may be difficult to separate from: (a) infantile pyknocytosis with associated thrombocytopenia (b) thrombocytopenia without prominent red cell changes. The condition finally diagnosed in children with MHA has included thrombotic microangiopathy ('haemolytic-uremic syndrome'), renal cortical necrosis, thrombotic thrombocytopenic purpura, chronic glomerulonephritis, giant haemangioma, Wilm's tumour, and pulmonary vascular disease. Prognosis is particularly poor in renal cortical necrosis and thrombotic thrombocytopenic purpura, the former running a fulminant course in which thrombocytopenia is more severe but red cell changes initially minimal. Sequential blood examinations require careful study under these circumstances. MHA usually indicates the presence of a microangiopathy associated with intravascular thrombosis; however, the latter is frequently unaccompanied by MHA, depending on the type of vessel involved and the presence or absence of blood flow through the involved vessel.

Infantile pyknocytosis in Mexican-American infants.

IN 1959 Tuffy et al1described 11 infants with a syndrome which they called infantile pyknocytosis. Seven of these infants had a clinical picture consistent with erythroblastosis fetalis; two of these seven infants required exchange transfusions, because of a bilirubin level over 20 mg/100 ml. Four other infants had no significant neonatal hyperbilirubinemia, but presented at 3 weeks of age with anemia or jaundice. Evidence of a hemolytic process persisted until 4 months, after which all abnormalities disappeared. The common denominator in these infants was the presence of abnormal erythrocytes in the peripheral blood called pyknocytes, or burr cells. All known forms of maternal isoimmunization were excluded. In one infant, the burr cells persisted following two exchange transfusions. One patient had diminished red blood cell glucose-6-phosphate dehydrogenase (RBC G-6-PD) activity, but this was felt to be an incidental finding. It was concluded that these patients had an extracorpuscular

Infantile pyknocytosis and glucose-6-phosphate dehydrogenase deficiency.

Infantile pyknocytosis and glucose-6-phosphate dehydrogenase deficiency.

Infantile pyknocytosis occurring in dissimilar twins.

Infantile pyknocytosis occurring in dissimilar twins.