Low Red Cell Research Articles

Inappropriately low red cell 2,3-diphosphoglycerate and p50 in transfused beta-thalassemia

The relationships among hemoglobin concentration (Hb), red cell 2,3-diphosphoglycerate (2,3-DPG), and p50 were studied in 20 chronically hypertransfused patients with thalassemia major. In the nontransfused control group, which included normal individuals as well as patients with sickle cell disease or iron deficiency anemia, the Hb correlated inversely with both 2,3-DPG concentration and p50, as is well established. In contrast, however, prior to transfusion, at the nadir of Hb, patients with thalassemia major had inappropriately low 2,3-DPG concentrations and p50s. These findings occurred in all patients, regardless of whether they had received packed, leukocyte-poor, or frozen-thawed red cells. The hypothesis that the time of blood storage was a factor was excluded by repeatedly transfusing one patient with packed red cells administered within 4 hr of collection in CPDA-1. A second hypothesis, that red cell function might be impaired by the iron-overloaded thalassemic environment, was excluded by studying a newly diagnosed, newly transfused patient with aplastic anemia. In both cases, the same inability to appropriately increase 2,3-DPG and p50 as the Hb fell during the intertransfusion interval was noticed. These data suggest that red cells of chronically transfused patients are unable to adapt to the decline in Hb that occurs during the intertransfusion interval.

Basic ferritin content of red cells of patients with anemia and polycythemia vera

Basic ferritin content of red cells has been evaluated with a simplified assay in subjects with various erythroid disorders. In 39 patients with iron deficiency anemia, red cell ferritin was significantly reduced compared with that of normal individuals. Thirty percent of these patients had low normal red cell ferritin content and the MCV for this group was significantly higher than that of patients with reduced red cell ferritin. The mean red cell ferritin of 30 subjects with the anemia of chronic disease was significantly reduced and patients in this group with normal red cell ferritin had higher plasma ferritin levels. In 14 patients with polycythemia vera, the mean red cell ferritin was significantly reduced and showed a positive correlation with the hemoglobin level and percent transferrin saturation. The red cell ferritin content of 9 individuals with acquired immune hemolytic anemia and 10 with acquired sideroblastic anemia was significantly elevated and, in subjects with immune hemolysis, showed a positive correlation with the reticulocyte count. These findings suggest a lack of discriminatory function for red cell ferritin in iron deficiency anemia and anemia of chronic disease. Evaluation of this parameter in the individual patient should take into account the presence of reticulocytosis.

Red cell folate levels, food antibodies and reticulin antibodies in farmer's lung — is there an association with coeliac disease?

Indirect evidence of enteropathy has been sought in a group of 57 subjects with farmer's lung (FL) by clinical questionnaire, estimation of red cell folate levels, the presence of precipitating antibodies to various food antigens and detection of reticulin antibodies. One subject was found who had villous atrophy and responded clinically to gluten withdrawal. There were two subjects with low red cell folate levels and multiple food antibodies, and one subject with reticulin antibodies and multiple food antibodies. Enteropathy is infrequent in subjects diagnosed clinically as having farmer's lung but seems to be more common than would be expected by chance. The mechanism has yet to be elucidated.

The effect of high or low oxygen affinity red cells on tissue oxygenation and myocardial function in hypoxic newborn lambs with or without hypercapnia.

In order to compare high and low oxygen affinity blood under conditions of severe respiratory failure, the effects of a high or low P50 were evaluated in two groups of newborn lambs (P50, 20 mmHg versus 30 mmHg), under conditions of hypoxic hypoxia (Fio2, 10%) and hypercapnic hypoxia (Fio2, 10% and Fico2, 10%). Data on cardiovascular function, blood gas parameters, and tissue oxygenation were collected under normoxic conditions and during severe hypoxia. During hypoxic hypoxia, a higher arterial oxygen content was noted in the high affinity group throughout the experiment; however, there were no significant differences detected in the remainder of the parameters studied. During hypercapnic hypoxia, the position of the oxygen dissociation curve did not cause any significant differences. When, however, hypercapnic hypoxia was compared to hypoxic hypoxia, there was a significant increase in cardiac output and myocardial contraction during hypercapnia.

DIETARY STATUS IN SOCIAL DRINKERS

AbstractA prospective study of light‐to‐moderate drinkers was undertaken to establish the frequency of abnormal findings on CT, psychometric and dietary parameters over a range of alcohol consumption. In particular, it was desirable to exclude the possibility of poor nutrition contributing to the picture of CT atrophy, especially with the assessment of any demonstrable reversibility. Thirty‐nine subjects were studied and 16 were found to be deficient in some part of their diet, although initial interviews established that they considered they took a balanced, adequate diet. Five subjects were re‐examined after six months' abstinence from alcohol: in four cases the total kilocalorie intake was less than the initial total, a proportion having been contributed latter by the previous alcohol consumption. The dietary history was partially checked by estimation of the level of B vitamins. Seven subjects had a low red cell thiamin, four of these having a normal serum level. These findings in social drinkers (mean alcohol consumption‡ 54 gms/day) lend support to the theory that thiamin deficiency in alcoholics is mediated by alcohol, rather than diet.

Red cell folate levels, food antibodies and reticulin antibodies in farmer's lung — is there an association with coeliac disease?

Indirect evidence of enteropathy has been sought in a group of 57 subjects with farmer's lung (FL) by clinical questionnaire, estimation of red cell folate levels, the presence of precipitating antibodies to various food antigens and detection of reticulin antibodies. One subject was found who had villous atrophy and responded clinically to gluten withdrawal. There were two subjects with low red cell folate levels and multiple food antibodies, and one subject with reticulin antibodies and multiple food antibodies. Enteropathy is infrequent in subjects diagnosed clinically as having farmer's lung but seems to be more common than would be expected by chance. The mechanism has yet to be elucidated.

Normal and clinical haematology in the yak (Bos grunniens)

Haematological examinations have been carried out on 21 clinically normal male and female adult yaks (Bos grunniens). Animals sedated with xylazine had significantly lower red cell counts, haemoglobin levels and packed cell volumes, fewer lymphocytes and higher monocyte counts than those bled while manually restrained. There were few significant sex differences. Several animals had eosinophilia associated with asymptomatic intestinal nematode infection. Haematological reference values were calculated for clinically normal, xylazine sedated and manually restrained yaks. These were used to identify haematological changes in 10 animals with various abnormal clinical signs. It was concluded that blood counts can provide valuable diagnostic information in this species.

HGMS studies of blood cell behavior in plasma

Magnetic behavior of human blood cells in plasma was studied in High Gradient Magnetic Separation (HGMS) with the single wire technique. Human venous blood was oxygenated or deoxygenated by passing it through a gas-permeable tubular membrane with oxygen or nitrogen gases on the outside. The rate of collection of red blood cells in the deoxygenated blood havinz Hematocrit 9 - 45% was determined by observing the increase in radius of cell collection on the wire. Effects of hematocrit and velocity of blood on buildup were determined. At low red cell concentration, the magnetic susceptibility of individual red blood cells was determined using trajectory analysis. Particles of unknown type were found with susceptibility values different from red blood cells. Diamagnetic behavior of white cells in plasma was confirmed. The experimental conditions of this study are more physiologic than the Saline dilution and chemical reducing agents employed by others in previous studies.

Interaction of L antibody with low potassium-type sheep red cells: resolution of two separate functional antibodies.

Antibodies of two specificities in alloimmune sheep anti-L sera, anti-Lp and anti-L1, were separated by a new technique and characterized. Absorption of anti-L serum with trypsinized LK(LL) sheep red cells left anti-Lp antibodies; the absorbed anti-L1 antibodies were then eluted. Anti-Lp was only weakly lytic in the presence of complement; it had no effect on passive K influx, but stimulated active K influx. The stimulation could be reversed by eluting the antibody in glycine buffer at low pH. Stimulatory activity in the eluted cells could be restored by resensitization with anti-Lp. Anti-L1 was more strongly lytic than anti-Lp in the presence of complement; it had no effect on active K influx, but inhibited passive K influx. Pig anti-ruminant IgG conjugated to hemocyanin was used to visualize by electron microscopy the number of Lp and L1 antigen sites on LL sheep red cells sensitized with anti-Lp an L1 antigen sites on LL sheep red cells sensitized with anti-Lp and anti-L1. The values obtained were 590 Lp sites/cell and 847 L1 sites/cell.

Plasma and red cell folate values and folate requirements in formula-fed term infants

Plasma and red cell folate concentrations (L. casei activity) and other pertinent blood values have been studied during the first year of life in 64 term infants. After weaning and until 6 months of age, 33 infants were given milk formula I (88 nmole [39 micrograms] folate per liter) and 31 infants MF II (178 nmole [78 micrograms] folate per liter). These infants were compared with 35 breast-fed term infants, considered to have an optimal folate status. The mean folate concentration in the human milk consumed at 3 months of age was 124 nmole (55 micrograms) per liter. The infants fed MF I had low plasma and red cell folate concentrations during the first months of life. The infants fed MF II had folate values almost comparable to those of the breast-fed infants. The weight gain in the infants fed MF II was significantly higher than observed in the infants fed MF I during the first 6 months of life. No significant differences related to folate deficiency were observed between the hemoglobin, RBC, and VPRC values in the formula-fed infants and those recorded in the breast-fed infants. It is estimated that the optimal folate intake during the first months of life in formula-fed infants is about 170 nmole (75 micrograms) per day. This amount is higher than previously recommended. Infants from all groups had folate intake similar to, or above, the minimal daily requirement needed for the erythropoiesis.

Hemoglobin Oleander [alpha 116(GH4)Glu replaced by Gln beta 2]: structural and functional characterization.

Hb Oleander [α116(GH4)Glun→Gln] was found in a newborn black infant and his mother during a screening program. Electrophoretically, Hb Oleander moves like Hb S on cellulose acetate, pH 8.5 and like Hb A on citrate agar, pH 6.0. The abnormal α chain moves cathodically to α G Philadelphia [α68(E17)Asn→Asp] at both pH 8.9 and 6.0. No clinical abnormalities were detected in either the mother or child, and the only hematologic abnormalities were low red cell indices and slight morphologic abnormalities of the erythrocytes. Oxygen equilibrium measurements under a variety of conditions yielded normal values. Specifically, Hb Oleander has a normal PCQ, cooperativity, and Bohr, chloride, and IHP effects. The substituted residue is externally situated in the molecule, with only one contact at the α1β1 interface.

The Toxicity of Guanidino Compounds in the Red Blood Cell in Uremia and the Effects of Hemodialysis

The presence of creatine, guanidinopropionic acid (GPA) and guanidinobutyric acid (GBA) was demonstrated in red blood cells from uremic patients; they were found only in trace amounts in red blood cells of normal controls. The levels of creatine, GPA and GBA in the red cell did not change during dialysis in contrast to the simultaneous decrease in plasma level. Both creatine and GPA inhibited glucose-6-phosphate dehydrogenase (G6PD) in vitro in physiological concentration, while creatine also activated erythrocyte transketolase (ETK). These effects are consistent with the low red cell G6PD level and high ETK activity that were observed in our uremic patients. The unchanging levels of creatine and GPA in the red cell despite hemodialysis may explain the continuing autohemolysis in otherwise adequately hemodialyzed end-stage renal failure patients.

Red cell phosphofructokinase and pyruvate kinase activities correlate with genetic variation of 2,3-bisphosphoglycerate in rats

Summary Rat strains have been isolated which have low red cell 2,3-bis-phosphoglycerate concentration and hemoglobin type BB , and high 2,3-bisphosphoglycerate concentration and hemoglobin types BB or AA . The genetic locus controlling red cell 2,3-bisphosphoglycerate concentration is closely-linked to the locus controlling hemoglobin type. Rats with low red cell 2,3-bisphosphoglycerate concentration also have relatively low red cell phosphofructokinase and pyruvate kinase activities. Kinetic studies suggest that the activity differences result from differences in Vmax . A proposed hypothesis suggests that an enzyme other than a glycolytic enzyme is coded by a gene closely-linked to the hemoglobin beta chain locus. Genetic variation in this enzyme then causes the activity differences in phosphofructokinase and pyruvate kinase between the low and high 2,3-bisphosphoglycerate red cells.

Passive potassium transport in low potassium sheep red cells: dependence upon cell volume and chloride.

The major pathway of passive K influx (ouabain-insensitive) was characterized in low-K type (LK) red cells of sheep. 1. Passive K transport in these cells was highly sensitive to variations in cell volume; it increased threefold or more in cells swollen osmotically by 10%, and decreased up to twofold in cells shrunken 5-10%. Active K influx was insensitive to changes in cell volume. Three different methods for varying cell volume osmotically all gave similar results. 2. The volume-sensitive pathway was specific for K in that Na influx did not vary with changes in cell volume. 3. The volume-sensitive K influx was a saturable function of external K concentration. It was slightly inhibited by Na, whereas K influx in shrunken cells was unaffected by Na. 4. Passive K influx was dependent on the major anion in the medium in that replacement of Cl with any of six other anions resulted in a reduction of K influx by 50-80% (replacement of Cl by Br caused an increase in K influx). The activation of K influx by Cl followed sigmoid kinetics. 5. Passive K influx is inhibited by anti-L antibody. The antibody affected only that portion of influx which was Cl-dependent and volume-sensitve. Of the subfractions of the antibody, it is anti-L1 which inhibits passive K transport. 6. Pretreatment of cells with iodoacetamide reduced the sensitivity of K influx to cell volume in that the influx was reduced in swollen IAA-treated cells and increased in shrunken IAA-cells. 7. Intracellular Ca has no role in altering passive K transport in LK sheep cells. Therefore, the major pathway of passive K transport in LK sheep red cells is sensitive to changes in cell volume, specific for K, dependent on Cl, and inhibited by anti-L1 antibody, The minor pathway, observed in shrunken cells, has none of these properties.

Vga: a new low incidence red cell antigen.

Abstract. A new low incidence red cell antigen, Van Vugt (Vga) has been found in a blood donor. A family study showed that the antigen is inherited as a Mendelian autosomal dominant character. Vga segregates independently from the MNSs blood group system. Only one example of the antigen was found on testing 17,209 blood donors. Anti‐Vga is not uncommon in sera containing multiple antibodies to low frequency antigens.

Effect of fetal or adult red cells on tissue oxygenation and myocardial function in normoxemic newborn lambs.

Twelve newborn lambs less than 48 hr old had their high oxygen affinity blood exchanged for low-affinity fresh adult blood. Tissue oxygenation, hemodynamic status, blood gases, and myocardial function were compared before and after the exchange transfusion. The P50 was increased from 18 to 29 mm Hg after exchange transfusion; pH and hemoglobin levels remained constant; and there was no change in myocardial function, arteriovenous O2 content difference, O2 consumption, or cardiac output. However, mixed venous PO2 was significantly increased with low affinity red cells (33 versus 23 mm Hg).

Red blood cell survival in patients with ventricular septal defect and patent ductus arteriosus.

Hemolysis of red blood cells (RBC) in stenotic or regurgitant cardiac valvular lesions has been felt to be due to mechanical trauma and shearing stress caused by turbulence of blood. RBC are also under a shearing stress from turbulence in high-pressure shunts, such as ventricular septal defect (VSD) and patent ductus arteriosus (PDA). The RBC survival time was measured in five patients with VSD and in 11 patients with PDA to determine if there was hemolysis of RBC. Six children without cardiac disease were also studied to obtain the control values for RBC survival times in th laboratory. Two patients with PDA were restudied one year postoperatively. Additional parameters studied were hemoglobin, packed cell volume, reticulocyte cell count, peripheral smear, and urinary hemosiderin. The hemoglobin values and the packed cell volumes were comparable in the two groups. The reticulocyte cell count was normal in all. Urinary hemosiderin was negative in all and the peripheral smear did not reveal abnormal red cell morphology. Mean red cell survival half-life in the two groups was identical. The red cell survival was abnormally low in two patients of PDA. Since one of these two patients had persistently low RBC survival postoperatively, the authors believe that the low red cell survival in this patient was unrelated to the presence of PDA. Based on findings in the small number of cases, the authors conclude that left to right shunt through a VSD or PDA is probably not associated with significant red blood cell destruction.

Plasma and red cell folate in newborn twins and their mothers in relation to gestational age.

Plasma and red blood cell folate concentrations (Lactobacillus casei activity) have been studied in 56 newborn twins and in 26 of their mothers, and in a control group consisting of 186 singletons and 155 of their mothers. The duration of the pregnancies ranged from 30-40 weeks. Iron, but no folic acid supplementation was given during pregnancy. The plasma and red cell folate concentrations in the twin mothers were at all stages of pregnancy similar to those observed in women with single pregnancies having an adequate folate intake. The twins had plasma folate concentrations similar to singletons at all gestational ages. Their red cell folate concentrations were lower than in singletons until 37 weeks of gestation, while the values were similar at term, indicating an increased transfer of folate to the twins during the last week of pregnancy. The smaller of the twins had similar plasma folate concentrations and lower red cell folate concentrations compared to the bigger one. At 30-32 weeks of pregnancy twin mothers had lower Hb, RBC and VPRC-values than women with single pregnancies. Twin mothers, delivering at 38-40 weeks of pregnancy, had values corresponding to those of single pregnancy women, probably indicating a recovery from a physiological lowering of the blood values. The twins had a similar Hb, lower RBC and higher MCV and reticulocyte values compared to singletons, possibly indicating a more active erythropoiesis in the twins. Folic acid supplementation is not recommended as a routine in twin pregnancies in this population. Twins delivered before term should be ensured an adequate folate intake.

Folic acid and mental symptoms in children with epilepsy.

312 children resident at a hospital school received a neuropsychiatric examination and information was provided on their IQ status. Children with a fall in their IQ were identified. Serum and red cell folate values were estimated and the relationship between neuropsychiatric disturbances and folate disturbances explored. Patients with a fall in IQ, neurotic disturbance and depression all had significantly lower serum folic acid levels than the rest of the population, and the children with neurotic disturbances and depression had significantly lower red cell folate values. The relationship between folic acid metabolism and the neuropsychiatric disturbances is discussed in the light of these findings.

Low glucose-6-phosphate dehydrogenase (G-6-PD) activity in red blood cells and susceptibility to copper-induced oxidative damage

The effects of copper on selected characteristics of blood from normal and G-6-PD deficient humans and sheep of the Dorset Strain (which also have comparable red cell G-6-PD activity units as G-6-PD deficient humans) were compared. Both the G-6-PD deficient humans and sheep were found to be markedly more sensitive to several indicators of oxidant stress as measured by increases in methemoglobin levels and decreases in the activity of red cell acetylcholinesterase. These findings indicate that susceptibility to copper-induced oxidative stress is associated with the presence of low red cell G-6-PD activity.