Umbilical Cord Red Blood Cells Research Articles

Iron Absorption and Partitioning During Pregnancy (OR35-03-19)

ObjectivesIron (Fe) homeostasis must be tightly regulated during pregnancy to supply sufficient Fe to both the mother and her developing fetus. Stable isotopes have been utilized to understand Fe absorption during pregnancy by measuring maternal red blood cell incorporation. This measure, however, underestimates the true amount of Fe absorbed, as dietary Fe is transferred to the fetus and may be retained by the placenta. The objective of this study was to obtain a more accurate estimation of Fe absorption during pregnancy and determine factors associated with Fe partitioning between the mom, baby and placenta. MethodsSixty-eight women (6 carrying multiple fetuses (age 27–33), 20 carrying singletons from Rochester NY (age 16–32), and 42 carrying singletons from Peru (age 18–30)) were dosed with an oral stable Fe isotope during late pregnancy. Iron absorption was calculated as the sum of tracer recovered in maternal and umbilical cord red blood cells (RBC) and for isotope retained in placental tissue. The net amount of Fe in each compartment was calculated based on Hb concentration, body (or placental) weight and estimated blood volume. Hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), folate and vitamin B-12 were assessed in maternal and cord blood. ResultsThe amount of maternally absorbed Fe was significantly greater when neonatal and placental uptake of tracer was accounted for (Table 1). While the majority (> 85%) of absorbed Fe tracer was utilized by the mother for RBC production, neglecting net Fe tracer transferred to the placenta and neonatal compartment underestimated true Fe absorption by 4%-20%. There was a significant positive association between the net amounts of Fe tracer recovered in the fetal compartment and the maternal compartment (R2 = 0.63, P < 0.001). Net Fe tracer retained in placental tissue was significantly positively associated with the net amount of Fe tracer present in the neonatal RBC pool at birth (P = 0.04). ConclusionsIron absorption was underestimated by up to 20% when absorbed Fe that was transferred to the fetus or retained by the placenta was not measured. More research on determinants of iron partitioning in pregnant women is needed to fully evaluate maternal Fe demands and absorption. Funding SourcesNational Institutes of Health, United States Department of Agriculture, Nestle Foundation. Supporting Tables, Images and/or Graphs▪▪

The Challenges of Daratumumab in Transfusion Medicine.

The field of transfusion medicine has evolved rapidly in recent years, but the central principle of transfusion is still simple, namely, the antigen-antibody interaction. Daratumumab (DARA), a monoclonal antibody (MoAb), was developed to treat relapsed/refractory multiple myeloma (RRMM). DARA works by targeting the CD38 portion of malignant cells; however, this drug attaches to the red blood cell (RBC) reagents used in blood banks, further complicating the antibody identification work-up. The AABB (formerly known as the American Association of Blood Banks) has issued a memorandum on how blood banks can effectively address panreactivity caused by DARA. Dithiothreitol (DTT), a common reagent in blood banks, has emerged as an inexpensive and practical way to dissolve panreactivity caused by DARA. However, DTT is known to destroy the Kell antigen blood group and other, less frequently encountered blood group antigens. Other promising alternative solutions, such as umbilical cord RBCs, screening cells, and neutralization, are not widely available yet. The exploration of these issues and options, in this review of the literature, is intended to guide blood bank technologists in dealing with panagglutination reactivity caused by DARA.

Safety and efficacy of allogeneic umbilical cord red blood cell transfusion for children with severe anaemia in a Kenyan hospital: an open-label single-arm trial

SummaryBackgroundIn sub-Saharan Africa, children are frequently admitted with severe anaemia needing an urgent blood transfusion, but blood is often unavailable. When conventional blood supplies are inadequate, allogeneic umbilical cord blood could be a feasible alternative. The aim of this study was to assess the safety and efficacy of cord blood transfusion in children with severe anaemia.MethodsBetween June 26, 2007, and May 20, 2008, 413 children needing an urgent blood transfusion were admitted to Kilifi District Hospital in Kenya. Of these, 87 children were eligible for our study—ie, younger than 12 years, no signs of critical illness, and haemoglobin 100 g/L or lower (if aged 3 months or younger) or 40 g/L or lower (if older than 3 months). Cord blood was donated at Coast Provincial General Hospital, Mombasa, and screened for transfusion-transmitted infections and bacterial contamination. Red blood cells were stored vertically at 2–6°C to enable sedimentation. After transfusion, children were monitored closely for adverse events and followed up for 28 days. The primary outcome measure was the frequency and nature of adverse reactions associated with the transfusion. Secondary outcomes were the changes in haemoglobin concentrations 24 h and 28 days after transfusion, compared with pretransfusion levels. This trial is registered on ISRCTN.com, number ISRCTN66687527.FindingsOf the 87 children eligible for the study, cord blood was unavailable for 24, six caregivers declined consent, and two children were withdrawn before transfusion. Therefore, 55 children received umbilical cord red blood cells from 74 donations. Ten (18%) children had ten serious adverse events and 43 (78%) had 94 adverse events; the most frequent adverse events were anaemia (n=14), weight loss (n=12), and vomiting (n=10). An independent expert panel judged none of these adverse events to be probably or certainly caused by the cord blood transfusion (one-sided 97·5% CI 0–6·5). Haemoglobin increased by a median of 26 g/L (IQR 21–31) 24 h after transfusion and by 50 g/L (10–68) a median of 29 days (28–35) after transfusion.InterpretationThese preliminary data suggest that cord blood could be an important supplementary source of blood for transfusion in children in sub-Saharan Africa. Further studies are needed to compare the safety and efficacy of cord blood with conventional adult-donated blood for transfusions. Challenges associated with cost, infrastructure, and scale up also need investigating.FundingWellcome Trust.

Mercury and heavy metal profiles of maternal and umbilical cord RBCs in Japanese population

Mercury (Hg) and other heavy metal profiles, namely, lead (Pb), arsenic (As), cadmium (Cd), and selenium (Se) were investigated in maternal and umbilical cord (cord) red blood cells (RBCs) at parturition in Japanese population. Correlation coefficients of Hg, Pb, As, Cd, and Se between maternal and cord RBCs were 0.91, 0.79, 0.89, 0.31, and 0.76, respectively, and the respective means of cord/maternal RBCs ratios were 1.63, 0.52, 0.62, 0.12, and 1.18. These results indicate that fetal exposure to these metals (excluding Cd) strongly reflected each maternal exposure level. Among these metals, the placental transfer of methylmercury (MeHg) seemed to be extremely high but that of Cd to be limited. Hg showed positive correlations with Se in maternal RBCs but not in cord RBCs, and the Se/Hg molar ratio was lower in the latter, suggesting that the protective effects of Se against MeHg are less expected in fetuses than in mothers.

Sodium potassium adenosine triphosphatase activity in preterm and term infants and its possible role in sodium homeostasis during maturation

AIMTo investigate sodium (NA+) potassium (K+) adenosine triphosphatase (ATPase) activity in newborn infants at different gestational ages, to elucidate the mechanism underlying poor renal sodium conservation in preterm infants.METHODSFifty three...

The murine monoclonal antibody NaM26-4C6 identifies a common structure on band 3 and glycophorin C.

The murine monoclonal antibody NaM26-4C6 (IgM class), obtained from the splenocytes of a BALB/c mouse immunized with human umbilical cord red blood cells, was characterized by agglutination test and immunoblotting analysis. The structure of the NaM26-4C6 epitope was further elucidated by using a series of peptides synthesized on pins. The antibody agglutinated untreated and chymotrypsin-treated but not trypsin- or neuraminidase-treated human erythrocytes. Agglutination-inhibition test demonstrated that the antibody recognizes an epitope located on the N-terminal trypsin-sensitive portion of glycophorin C. The antibody bound on immunoblots to glycophorin C, and also to the band 3 protein and its 69-kDa N-terminal fragment but did not bind to desialylated and de-O-glycosylated glycophorin C. Peptide mapping allowed localization of the binding site on the 23-kDa N-terminal intracellular peptide of band 3. The antibody binds to the amino-acid sequences 22EDPDIP27 of band 3 protein and 15SLEPDPGM22 of glycophorin C, and residues D and P were found to be essential. The new epitope identified by NaM26-4C6 corresponds to a linear amino acid sequence located on the N-terminal intracellular portion of band 3 and to a more complex structure involving oligosaccharide chains on the N-terminal extracellular domain of GPC.

Alloantibody‐Induced Impaired Neonatal Expression of a Red Blood Cell Antigen Associated with Maternal Alloimmunization

Abstract. Animals genetically capable of making certain gene products have been shown to have the production of such products completely or partially suppressed by exposure in utero or neonatally to antibodies specific for that gene product. This alloantibody‐induced depression of expression of a specific antigenic determinant has yet to be shown to occur in man. The McCoya red blood cell antigen is reported to be well developed at birth. However, 2 children born to mothers with high‐titer McCoya antibodies in their serum, phenotyped as McCoy (a−) at birth and, on retesting their red blood cells, 1 at 5 months and the 2nd at 11 months, both phenotyped as McCoy (a+). It is possible that this lack of expression of the McCoya antigen at birth represents a characteristic of an obligate heterozygote. However, on testing 50 random umbilical cord red blood cell samples with two potent McCoya antisera, only 1 was found to be negative. If the negative phenotpye were a characteristic of an obligate heterozygote at birth, then the neonatal incidence of the McCoy (a−) phenotype should have been significantly (p&lt;10−4) higher in our random cord blood sample than observed (expected 11). The impaired expression of the McCoya antigen on the red blood cells of these 2 infants at birth, in conjunction with evidence of maternal alloimmunization, strongly suggests alloantibody‐induced antigenic suppression of the McCoya antigen as a probable cause.

Alloantibody‐Induced Impaired Neonatal Expression of a Red Blood Cell Antigen Associated with Maternal Alloimmunization

Animals genetically capable of making certain gene products have been shown to have the production of such products completely or partially suppressed by exposure in utero or neonatally to antibodies specific for that gene product. This alloantibody-induced depression of expression of a specific antigenic determinant has yet to be shown to occur in man. The McCoya red blood cell antigen is reported to be well developed at birth. However, 2 children born to mothers with high-titer McCoya antibodies in their serum, phenotyped as McCoy (a-) at birth and, on retesting their red blood cells, 1 at 5 months and the 2nd at 11 months, both phenotyped as McCoy (a+). It is possible that this lack of expression of the McCoya antigen at birth represents a characteristic of an obligate heterozygote. However, on testing 50 random umbilical cord red blood cell samples with two potent McCoya antisera, only 1 was found to be negative. If the negative phenotype were a characteristic of an obligate heterozygote at birth, then the neonatal incidence of the McCoy (a-) phenotype should have been significantly (p less than 10(-4)) high in our random cord blood sample than observed (expected 11). The impaired expression of the McCoya antigen on the red blood cells of these 2 infants at birth, in conjunction with evidence of maternal alloimmunization, strongly suggests alloantibody-induced antigenic suppression of the McCoya antigen as a probable cause.

Alloantibody-Induced Impaired Neonatal Expression of a Red Blood Cell Antigen Associated with Maternal Alloimmunization

Animals genetically capable of making certain gene products have been shown to have the production of such products completely or partially suppressed by exposure in utero or neonatally to antibodies specific for that gene product. This alloantibody-induced depression of expression of a specific antigenic determinant has yet to be shown to occur in man. The McCoy^a red blood cell antigen is reported to be well developed at birth. However, 2 children bom to mothers with high-titer McCoy^a antibodies in their serum, phenotyped as McCoy (a-) at birth and, on retesting their red blood cells, 1 at 5 months and the 2nd at 11 months, both phenotyped as McCoy (a+). It is possible that this lack of expression of the McCoy^a antigen at birth represents a characteristic of an obligate heterozygote. However, on testing 50 random umbilical cord red blood cell samples with two potent McCoy^a antisera, only 1 was found to be negative. If the negative phenotpye were a characteristic of an obligate heterozygote at birth, then the neonatal incidence of the McCoy (a-) phenotype should have been significantly (p<10^-4) higher in our random cord blood sample than observed (expected 11). The impaired expression of the McCoy^a antigen on the red blood cells of these 2 infants at birth, in conjunction with evidence of maternal alloimmunization, strongly suggests alloantibody-induced antigenic suppression of the McCoy^a antigen as a probable cause.

Switching of the nonallelic forms of fetal hemoglobin during late gestation

The gamma chains of human fetal hemoglobin occur in two nonallelic forms, designated G gamma and A gamma, which differ from one another in having either glycine or alanine as their 136th residue respectively. In newborns, G gamma comprises about 75% of the total gamma chains, while in adults, G gamma comprises about 40% of the total gamma chains. The timing of the switching events that lead to the alteration of the rates of production of G gamma and A gamma are still unknown. Umbilical cord red blood cells from term infants were separated by density gradient fractionation into four age-dependent fractions. Red blood cell size and reticulocyte content decreased and the percent fetal hemoglobin increased with increasing gradient densities, confirming age- dependent density separation. The percent G gamma was determined by two methods on fractionated cord red blood cells to determine if the switch in the production ratio of the nonallelic forms of gamma chains began during late gestation. The G gamma content of fetal hemoglobin was found to decrease with decreasing red blood cell age, demonstrating that the switch from predominately glycine-containing gamma chains to predominately alanine-containing gamma chains begins during late gestation.

Switching of the Nonallelic Forms of Fetal Hemoglobin During Late Gestation

AbstractThe gamma chains of human fetal hemoglobin occur in two nonallelic forms, designated Gγ and Aγ, which differ from one another in having either glycine or alanine as their 136th residue respectively. In newborns, Gγ comprises about 75% of the total gamma chains, while in adults, Gγ comprises about 40% of the total gamma chains. The timing of the switching events that lead to the alteration of the rates of production of Gγ and Aγ are still unknown. Umbilical cord red blood cells from term infants were separated by density gradient fractionation into four age-dependent fractions. Red blood cell size and reticulocyte content decreased and the percent fetal hemoglobin increased with increasing gradient densities, confirming age-dependent density separation. The percent Gγ was determined by two methods on fractionated cord red blood cells to determine if the switch in the production ratio of the nonallelic forms of gamma chains began during late gestation. The Gγ content of fetal hemoglobin was found to decrease with decreasing red blood cell age, demonstrating that the switch from predominately glycine-containing gamma chains to predominately alanine-containing gamma chains begins during late gestation.

Assessment of complement binding by anti-D and anti-M antibodies employing labelled antiglobulin antibodies.

The presence of small amounts of C3d on freshly obtained normal red blood cells (RBC) was demonstrated by a radio-labelled antiglobulin technique; this increased 1.5-fold after incubation in fresh normal serum. No significant further increase in bound C3d was demonstrated for cDE/cDE, CDe/CDe, -D-/-D- RBC maximally sensitized with any of three potent anti-D antibodies. When anti-c, anti-D and anti-E antibodies were used in combination to sensitize cDE/cDE RBC, bound C3d increased by approximately 22%; however, a similar increase occurred with cde/cde RBC and was therefore considered non-Rh specific. Umbilical cord RBC from four infants severely affected by anti-D haemolytic disease of the newborn did not exhibit more bound C3d than cord RBC from normal controls. One serum containing IgM anti-M bound a small amount of complement in vitro; two IgG anti-M sera did not.