Value of Estimating Methylmalonic Acid Excretion in Anaemia

A rapid technique suitable for routine pathology laboratories has been used to estimate methylmalonic acid excretion in a 24-hour urine collection following a 10g. valine load. Levels above 40 mg./24 hours were found only in patients with vitamin B₁₂ deficiency. Patients with pernicious anaemia treated more than 24 hours before urine collection and patients with other types of anaemia had methylmalonic acid levels below 25 mg./24 hours.This method of demonstrating vitamin B₁₂ deficiency can be applied rapidly in debilitated patients so that specific treatment can be instituted within 36 hours of admission.     

Intrinsic-factor Antibody and Absorption of Vitamin B12 in Pernicious Anaemia

The mean urinary excretion in a vitamin-B₁₂ absorption (Schilling) test in control subjects was 19·2% and in pernicious anaemia when given with additional intrinsic factor was as follows: no intrinsic-factor antibodies demonstrable 19·3%, antibodies in serum only 14·4%, antibodies in gastric juice only 11·1%, and antibodies in both serum and gastric juice 8·4%. It is concluded that intrinsic-factor antibody exerts an adverse effect on vitamin-B₁₂ absorption in most patients with pernicious anaemia.     

Dissociation of Intrinsic Factor from its Antibody: Application to Study of Pernicious Anaemia Gastric Juice Specimens

Intrinsic factor antibody may sometimes be concealed in the gastric secretions of pernicious anaemia subjects, being complexed with residual amounts of intrinsic factor.A method is described for dissociating intrinsic factor from its antibody. Antibody to the vitamin-B₁₂-binding site of intrinsic factor was identified in 16 (57%) out of 28 samples of pernicious anaemia gastric juice after dissociation but in only 10 before dissociation. There was no clear relationship between the incidence of antibody in the serum and in the gastric juice of these patients.     

Screening of Psychiatric Patients for Hypovitaminosis B12

Vitamin B₁₂ assays and inspection of peripheral blood films performed on 1,004 consecutive new patients over the age of 50 admitted to mental hospital led to the discovery of pernicious anaemia in only two cases. It is concluded that routine vitamin B₁₂ assays are justified only when fully-automated techniques have become available.     

Vitamin B12 Status in Pregnancy among Immigrants to Britain

Haemoglobin, serum vitamin B₁₂, and serum and red cell folate levels have been measured in 322 pregnant immigrant women in London at their first booking and in a proportion at 34 weeks of gestation and postnatally. The Indian, East-African Indian, and Pakistani and Bangladeshi patients showed significantly lower initial mean serum vitamin B₁₂ levels than the European group, the levels being lower in Hindu and Sikh patients than in Moslems. The patients of West Indian, Indian, and East-African Indian origin showed significantly lower initial mean haemoglobin levels than the immigrants from European countries. Though there was no overall correlation between haemoglobin and serum vitamin B₁₂ level the incidence of hypersegmented polymorphs and macrocytosis in the peripheral blood was highest in the Indian and East-African Indian patients, and both these features were particularly frequent in patients with subnormal serum vitamin B₁₂ levels. Only one patient, however, had overt megaloblastic anaemia due to vitamin B₁₂ deficiency. The Indian patients whose red cell folate levels were less than 200 ng/ml also had a lower mean serum vitamin B₁₂ level than those with red cell folate levels greater than 200 ng/ml. The Indian patients had smaller babies than the Europeans but this was not related to the differences in vitamin B₁₂ status between the two groups. However, out of 39 babies of the Indian group 5 (13%) showed subnormal serum vitamin B₁₂ levels in the first 10 days of life, the lowest level being 120 pg/ml.Though there was an overall statistically significant fall in serum vitamin B₁₂ between first booking and 34 weeks of pregnancy there was no significant fall in serum vitamin B₁₂ in those who initially had subnormal levels. Thus many Indian women are vitamin B₁₂ deficient in pregnancy, and this is associated with morphological blood abnormalities in many cases, but megaloblastic anaemia due to this deficiency is relatively infrequent.     

Utilization of Iron Dextran

The utilization of iron dextran was investigated in normal subjects, in patients with iron-deficiency anaemia, and in anaemias associated with rheumatoid arthritis, reticulosis, and uraemia. Utilization of iron for haemoglobin formation at 14 days was found to be depressed in patients with rheumatoid arthritis, reticulosis, and uraemia, but when a concomitant iron-deficiency anaemia was present utilization was significantly increased. When iron dextran is used to treat anaemias in such conditions an optimum therapeutic response will be obtained only when bone marrow iron stores are absent.     

Serum Gastrin in Chronic Gastritis

Fasting gastrin levels in serum were measured in 49 patients with different types of chronic gastritis and in matched controls. In 15 patients with established pernicious anaemia the mean (± S.E. of mean) level of gastrin was greatly raised (699 ± 99 pg/ml). In 17 patients with chronic atrophic gastritis, seropositive for parietal cell antibody but with adequate vitamin-B₁₂ absorption, the level was also raised (476 ± 74 pg/ml). By contrast, in “simple” atrophic gastritis seronegative for parietal cell antibody the gastrin levels were significantly lower for both diffuse atrophic gastritis (129 ± 31 pg/ml) and multifocal gastritis (14 ± 4 pg/ml). These levels were similar to those in the controls (46 ± 7 pg/ml).The mechanism of the raised gastrin levels remains uncertain, but neither achlorhydria nor in vivo action of the parietal cell antibody wholly accounted for the hypergastrinaemia.We conclude that hypergastrinaemia is characteristic of gastritis associated with autoimmune reactions to gastric antigens and pernicious anaemia and that a raised serum gastrin is a useful marker of the type of gastritis that tends to progress to the gastric lesion of pernicious anaemia. The findings suggest that this type of gastritis is an essentially different disease from “simple” atrophic gastritis, and the differences in gastrin levels may be due to sparing of the antral mucosa in the autoimmune type but not in “simple” gastritis.     

Autoimmune Haemolytic Anaemia and Mefenamic Acid Therapy

Three patients developed autoimmune haemolytic anaemia while being treated with mefenamic acid. In each case the autoimmune haemolytic anaemia was of the warm antibody γG type, and the antibodies had some rhesus specificity. All three patients recovered when the drug was withdrawn.Attempts to inhibit or enhance the activity of the antibody in vitro were unsuccessful.Direct antihuman globulin tests were made in.the red cells of 36 patients receiving long-term mefenamic acid therapy, but only one was found to be transitorily positive.     

THE NUMBER AND POSSIBLE FUNCTIONS OF DNA-SYNTHESIZING CELLS IN HUMAN BLOOD

The number of DNA-synthesizing cells in the blood of patients with various disorders was studied autoradiographically after incubation of blood in vitro with [³H]thymidine. The DNA-synthesizing cells were cytologically assigned to the following categories: erythroid, myeloid, lymphoplasmacytoid and unidentifiable (monocytoid or blast-like) cells. The following patient categories were studied: mitral valvular disease (samples obtained from peripheral vein, pulmonary artery and left auricle), ‘autoimmune diseases’(systemic lupus erythematosus, schleroderma, Hashimoto's thyroiditis, immunohaemolytic anaemia), patients with depressed haemopoiesis (aplastic anaemia, nitrogen-mustard induced bone-marrow hypoplasia) and with increased haemopoiesis (haemolytic anaemia, pernicious anaemia before and during initial vitamin-B₁₂ therapy, red-cell mass regeneration after haemorrhage or iron deficiency) and patients with bacterial infection. In all conditions studied, the number of labelled monocytoid and blast-like cells varied between 0 and 4/μl. Similarly, the number of labelled lympho-plasmo-cytoid cells was consistently low (0–8/μl) in all cases studied except two, where values of 37 and 63/μl were found. Both these patients had severe bacterial infections. The function(s) and potential(s) of these cells are discussed. The fate of the blast-like and monocytoid cells remains obscure. The lympho-plasmocytoid cells probably serve an immunological function, perhaps by disseminating immune responses. Whether or not some DNA-synthesizing cells in the blood are haemopoietic stem cells cannot be decided from the available evidence.     

Implication of therapeutic outcomes associated with molecular characterization of paediatric aplastic anaemia

ObjectivesSevere aplastic anemia is characterized by a hypocellular bone marrow and peripheral cytopenia. Mesenchymal stem cells (MSCs) play a crucial role in haematopoietic stem cells (HSCs) development and the development of microenvironment suitable for hematopoiesis. Molecular characterization of telomere maintenance pathway and gene expression profiling of MSCs can be important for the therapeutic interventions among paediatric aplastic anaemia patients.MethodsThe study involved paediatric aplastic anaemia patients (n = 10) and age matched paediatric healthy donors (n = 8). Peripheral blood samples were collected from the individuals. Average leucocyte telomere length and gene expression of the telomere maintenance genes were determined by quantitative real time PCR. Microarray based gene expression profiles (GSE33812) of MSCs for five paediatric aplastic anaemia patients were analyzed compared to five healthy controls and the data was downloaded from the GEO database.ResultsThe telomere length was significantly shorter among paediatric AA patients compared to age matched healthy donors. Interestingly, one subgroup (n = 2) of paediatric AA patients has moderate telomere length comparable to age matched healthy donors. Based on the gene expression analysis of telomere maintenance pathway, TERF2 was significantly downregulated among paediatric patients with shorter telomere length but not among paediatric patients with moderate telomere length. Gene expression profiling of MSCs revealed three differentially expressed genes (GAS2L3, MK167 and TMSB15A) among the patients and was associated with therapeutic outcome.ConclusionTelomere length estimation and gene expression patterns of the MSCs and telomere length maintenance pathway may serve as a potential biomarker and could be associated with therapeutic choice of paediatric aplastic anaemia patients.     

Mapping the risk of anaemia in preschool-age children: the contribution of malnutrition, malaria, and helminth infections in West Africa

Background

Childhood anaemia is considered a severe public health problem in most countries of sub-Saharan Africa. We investigated the geographical distribution of prevalence of anaemia and mean haemoglobin concentration (Hb) in children aged 1–4 y (preschool children) in West Africa. The aim was to estimate the geographical risk profile of anaemia accounting for malnutrition, malaria, and helminth infections, the risk of anaemia attributable to these factors, and the number of anaemia cases in preschool children for 2011.

Methods and Findings

National cross-sectional household-based demographic health surveys were conducted in 7,147 children aged 1–4 y in Burkina Faso, Ghana, and Mali in 2003–2006. Bayesian geostatistical models were developed to predict the geographical distribution of mean Hb and anaemia risk, adjusting for the nutritional status of preschool children, the location of their residence, predicted Plasmodium falciparum parasite rate in the 2- to 10-y age group (Pf PR_2–10), and predicted prevalence of Schistosoma haematobium and hookworm infections. In the four countries, prevalence of mild, moderate, and severe anaemia was 21%, 66%, and 13% in Burkina Faso; 28%, 65%, and 7% in Ghana, and 26%, 62%, and 12% in Mali. The mean Hb was lowest in Burkina Faso (89 g/l), in males (93 g/l), and for children 1–2 y (88 g/l). In West Africa, severe malnutrition, Pf PR_2–10, and biological synergisms between S. haematobium and hookworm infections were significantly associated with anaemia risk; an estimated 36.8%, 14.9%, 3.7%, 4.2%, and 0.9% of anaemia cases could be averted by treating malnutrition, malaria, S. haematobium infections, hookworm infections, and S. haematobium/hookworm coinfections, respectively. A large spatial cluster of low mean Hb (<80 g/l) and maximal risk of anaemia (>95%) was predicted for an area shared by Burkina Faso and Mali. We estimate that in 2011, approximately 6.7 million children aged 1–4 y are anaemic in the three study countries.

Conclusions

By mapping the distribution of anaemia risk in preschool children adjusted for malnutrition and parasitic infections, we provide a means to identify the geographical limits of anaemia burden and the contribution that malnutrition and parasites make to anaemia. Spatial targeting of ancillary micronutrient supplementation and control of other anaemia causes, such as malaria and helminth infection, can contribute to efficiently reducing the burden of anaemia in preschool children in Africa. Please see later in the article for the Editors'' Summary     

Predictors of Persistent Anaemia in the First Year of Antiretroviral Therapy: A Retrospective Cohort Study from Goma,the Democratic Republic of Congo

Background

Anaemia is associated with adverse outcomes including early death in the first year of antiretroviral therapy (ART). This study reports on the factors associated with persistent anaemia among HIV-infected patients initiating ART in the Democratic Republic of Congo (DR Congo).

Methods

We conducted a retrospective cohort study and analyzed data from patients receiving HIV care between January 2004 and December 2012 at two major hospitals in Goma, DR Congo. Haemoglobin concentrations of all patients on ART regimen were obtained prior to and within one year of ART initiation. A logistic regression model was used to identify the predictors of persistent anaemia after 12 months of ART.

Results

Of 756 patients, 69% of patients were anaemic (IC95%: 65.7–72.3) at baseline. After 12 months of follow up, there was a 1.2 g/dl average increase of haemoglobin concentration (P < 0.001) with differences depending on the therapeutic regimen. Patients who received zidovudine (AZT) gained less than those who did not receive AZT (0.99 g/dl vs 1.33 g/dl; p< 0.001). Among 445 patient who had anaemia at the beginning, 33% (147/445) had the condition resolved. Among patients with anaemia at ART initiation, those who did not receive cotrimoxazole prophylaxis before starting ART(AOR 3.89; 95% CI 2.09–7.25; P < 0.001) and a AZT initial regimen (AOR 2.19; 95% CI 1.36–3.52; P < 0.001) were significantly at risk of persistent anaemia.

Conclusions

More than two thirds of patients had anaemia at baseline. The AZT-containing regimen and absence of cotrimoxazole prophylaxis before starting ART were associated with persistent anaemia 12 months, after initiation of treatment. Considering the large proportion of patients with persistence of anaemia at 12 months, we suggest that it is necessary to conduct a large study to assess anaemia among HIV-infected patients in Goma.     

T-lymphocyte colony formation by lymphocytes from patients with aplastic anaemia

T-lymphocyte colonies were cultured using lymphocytes from patients with aplastic anaemia and normal donors to assess their respective proliferative activities. Colony numbers from aplastic patient's cells were lower than from normal donors', though this was not significant. When lymphocytes from patients were co-cultured with normal lymphocytes, inhibition of T-colony formation was observed in 8 out of 12 experiments. As the degree of inhibition was greater than if patient cells grew no colonies, then, clearly, normal T-colony formation was inhibited. This ability of patients' lymphocytes to suppress lymphopoiesis might account for the low levels of patient T-colony formation, as well as low in vivo numbers of lymphocytes found in patients with aplastic anaemia. The role of patients' lymphocytes in causing marrow aplasia was investigated. Although the incorporation of patients' lymphocytes in normal granulocyte-macrophage (GM) colony-forming systems inhibited colony growth, in only 1 out of 8 patients was this inhibition significantly greater than that caused by the addition of normal lymphocytes to GM colony systems. Therefore, lymphocytes may not be the primary cause of aplastic anaemia, except for a few rare cases.     

Complex genesis of anemia in chronic liver diseases]

36% of a total of chronic liver patients suffered from anaemia and 50.5% of patients affected with liver cirrhosis. In most cases the anaemias were normochrome and hypochrome or hyperchrome only in some cases. In analyzing possible single factors the reductions of vitamin B12 absorption could be made probable by means of the Schilling test and sometimes a folic acid deficiency in macrocyte anaemia with normal vitamin B12 absorption by determining the folic acid content in the serum and by successes of test treatment 82% of patients with liver cirrhosis showed a latent or manifest haemolysis. However, it was only in 1/3 of the patients with liver cirrhosis that the spleen turned out to be the place of an increased degradation of erythrocytes. In some cases an increased erythrocytoclasia into the liver could be identified. Predominantly, however, an increased degradation of erythrocytes in the total RHS had to be assumed. Twice an ineffective erythropoiesis could be found by ferrokinetic examinations. As a whole ferrokinetic examinations cannot be interpreted easily, because their static and dynamic values of iron transport in the plasma volume of liver patients will undergo considerable changes. Patients with disturbances of haematopoiesis and with haemolysis remaining in the latent stage may develop a manifest anaemia because of the influence of additional factors, such as increase of the plasma volume at lowered haematocrit value or microbleedings. The cause of anaemia cannot be concluded with sufficient probability from the type of anaemia; in a single case all pathogenetic factors will rather have to be analyzed. Therapeutic possibilities for hepatogenous anaemia of complex genesis are discussed.     

Red cell ferritin content: a re-evaluation of indices for iron deficiency in the anaemia of rheumatoid arthritis.

In iron deficiency anaemia basic red cell content of ferritin is appreciably reduced. This variable was determined in 62 patients with rheumatoid arthritis to evaluate conventional laboratory indices for iron deficiency in the anaemia of rheumatoid arthritis. For 23 patients with rheumatoid arthritis and normocytic anaemia irrespective of plasma ferritin concentration, red cell ferritin content did not differ significantly from that for non-anaemic patients with rheumatoid arthritis. For 27 patients with rheumatoid arthritis and microcytic anaemia, the mean red cell ferritin content for patients with a plasma ferritin concentration in the 13-110 micrograms/l range was appreciably reduced. It was indistinguishable from that for patients with rheumatoid arthritis and classical iron deficiency anaemia, indicated by plasma ferritin concentrations of less than 12 micrograms/l. In contrast, the mean red cell ferritin content for patients with rheumatoid arthritis, microcytic anaemia, and plasma ferritin concentrations above 110 micrograms/l did not differ from that for patients with rheumatoid arthritis and normocytic anaemia. Oral treatment with iron in patients with rheumatoid arthritis, microcytic anaemia, and appreciably reduced red cell ferritin concentrations was accompanied by significant increases in haemoglobin concentration (p less than 0.01), mean corpuscular volume (p less than 0.01), and red cell ferritin contents (p less than 0.05). This treatment, however, did not produce any appreciable change in haemoglobin concentration in patients with rheumatoid arthritis, normocytic anaemia, and normal red cell ferritin contents. These findings suggest that the indices for iron deficiency in patients with rheumatoid arthritis and anaemia should include peripheral blood microcytosis together with a plasma ferritin concentration of less than 110 micrograms/l.     

Prevalence and Risk Factors of Anaemia among Children Aged between 6 Months and 14 Years in Kenya

Background

Anaemia is one of the significant public health problems among children in the world. Understanding risk factors of anaemia provides more insight to the nature and types of policies that can be put up to fight anaemia. We estimated the prevalence and risk factors of anaemia in a population-based, cross-sectional survey.

Methodology

Blood samples from 11,711 children aged between 6 months and 14 years were collected using a single-use, spring-loaded, sterile lancet to make a finger prick. Anaemia was measured based on haemoglobin concentration level. The generalized linear model framework was used to analyse the data, in which the response variable was either a child was anemic or not anemic.

Results

The overall prevalence of anaemia among the children in Kenya was estimated to be 28.8%. The risk of anaemia was found to decrease with age progressively with increase in each year of age; children below 1 year were at highest risk of anaemia. The risk of anaemia was significantly higher in male than female children. Mothers with secondary and above education had a protective effect on the risk of anaemia on their children. Malaria diagnosis status of a child was positively associated with risk anaemia.

Conclusion

Controlling co-morbidity of malaria and improving maternal knowledge are potential options for reducing the burden of anaemia.     

The development and role of international biological reference materials in the diagnosis of anaemia

Anaemia is a major global health problem. Although the main cause is iron deficiency, anaemia also results from other nutritional deficiencies (folate and vitamin B₁₂), haemolytic disorders including haemoglobinopathies, and bone marrow disorders. Accurate diagnosis of anaemia is dependent on reliable diagnostic tests and reference ranges, which in turn are dependent on effective standardisation. Standardisation is achieved through the availability of reference materials and reference measurement procedures. International biological reference materials have therefore been developed to standardise and control diagnostic tests for anaemia for a diverse range of analytes including total haemoglobin and haemoglobin types, ferritin, the serum transferrin receptor, serum vitamin B₁₂ and folate, whole blood folate, and alloantibodies which mediate immune haemolytic anaemia.     

Correlation of anaemia and cognitive functions measured by the complex reactiometer Drenovac

Cognitive impairment impinges significantly on the quality of life. Previous research revealed that anaemia can have a major influence on cognitive functioningt. The article is a correlational study examining the relationship between anaemia levels and cognitive functioning in adult patients. Sixty-one patients (both inpatients and outpatients), among them 30 anemic and 31 non-anaemic, 33 female and 28 male, aged 32-60 (median 43) treated at the Dept. of Hematology, Clinical Hospital Center Rijeka, Croatia were analysed according to hemoglobin (Hb) level and cognitive ability. Assessment of cognition (convergent inductive thinking) was performed by the Complex reactiometer Drenovac (CRD). The results showed that anaemia significantly undermines cognitive functions in adult patients (p < 0.01). Even in non-anaemic patients (Hb higher than 120 g/L), Hb level is related to better cognitive ability.     

Anciano y anemia: revisión crítica de su definición y prevalencia

Background and objectivesThe prevalence of anaemia is an important health indicator, although there is little rigorous information gathered on the elderly population, particularly in those over 80 years old. The same criteria that are used in the general population are often used to define anaemia in the elderly. The epidemiological data collected by the WHO in 1968 (that have been used to generalise this criteria), did not include the population over 65 years-old.Two objectives are established, which includes a critical review of the available evidence on whether the criteria used to define anaemia in the adult population can be extrapolated to the elderly, and a review of publications on the prevalence of anaemia in the elderly over 80 years-old.Material and methodsA systematic bibliographic search was performed on the established objectives.ResultsAlthough the WHO criteria, based on data from 1968, are widely used, other possible cut-off points have been proposed for elderly people. A total of 20 studies were found that were conducted in North America and Europe, with only 70,000 patients, and different age criteria. The prevalence of anaemia ranges between 3% and 63%, depending on the diagnostic criteria, age, and whether they were institutionalised or not.ConclusionsAnaemia is a very prevalent disease in elderly patients. The collection of large databases is necessary to determine more adequate diagnostic criteria.     

Severe anaemia is associated with a higher risk for preeclampsia and poor perinatal outcomes in Kassala hospital,eastern Sudan

Background

Anaemia during pregnancy is major health problem. There is conflicting literature regarding the association between anaemia and its severity and maternal and perinatal outcomes.

Methods

This is a retrospective case-control study conducted at Kassala hospital, eastern Sudan. Medical files of pregnant women with severe anaemia (haemoglobin (Hb) < 7 g/dl, n = 303) who delivered from January 2008 to December 2010 were reviewed. Socio-demographic and obstetric data were analysed and compared with a similar number of women with mild/moderate anaemia (Hb = 7-10.9 g/dl, n = 303) and with no anaemia (Hb > 11 g/dl, n = 303). Logistic regression analysis was performed separately for each of the outcome measures: preeclampsia, eclampsia, preterm birth, low birth weight (LBW) and stillbirth.

Results

There were 9578 deliveries at Kassala hospital, 4012 (41.8%) women had anaemia and 303 (3.2%) had severe anaemia. The corrected risk for preeclampsia increased only in severe anaemia (OR = 3.6, 95% CI: 1.4-9.1, P = 0.007). Compared with women with no anaemia, the risk of LBW was 2.5 times higher in women with mild/moderate anaemia (95% CI: 1.1-5.7), and 8.0 times higher in women with severe anaemia (95% CI: 3.8-16.0). The risk of preterm delivery increased significantly with the severity of anaemia (OR = 3.2 for women with mild/moderate anaemia and OR = 6.6 for women with severe anaemia, compared with women with no anaemia). The corrected risk for stillbirth increased only in severe anaemia (OR = 4.3, 95% CI: 1.9-9.1, P < 0.001).

Conclusions

The greater the severity of the anaemia during pregnancy, the greater the risk of preeclampsia, preterm delivery, LBW and stillbirth. Preventive measures should be undertaken to decrease the prevalence of anaemia in pregnancy.