Distribution of hemoglobin levels and prevalence of anemia according to sex, age group, and region in 13 Korean cities.

INTRODUCTION: The distribution of hemoglobin (Hb) levels and the prevalence of anemia are significant public health indicators. The aims of this study were to determine the distribution of Hb levels and the prevalence of anemia according to sex, age group, and region throughout Korea. METHODS: The study analyzed data on 1 159 298 subjects who received health checkups at 16 health-promotion centers in 13 Korean cities during 2018. Anemia and its severity were defined according to the World Health Organization classification for Hb levels as follows: mild anemia (11-12.9 g/dL in males and 11-11.9 g/dL in females), moderate anemia (10-10.9 g/dL in both sexes), and severe anemia (<10.0 g/dL in both sexes). RESULTS: The Hb level in the general sample was lower in females (13.25 ± 1.13 g/dL, mean ± SD) than in males (15.29 ± 1.22 g/dL). The overall prevalence of anemia was 6.0% (2.98% in males and 8.56% in females), and the prevalence of severe anemia was 0.92% (0.23% in males and 1.51% in females). While the prevalence of anemia increased monotonically with age in males, it was bimodal in females with two peaks at 40-49 years and ≥80 years. The highest prevalence of anemia in females aged 40-49 years was attributed to microcytic anemia, while increases in anemia prevalence in males aged ≥50 years and females aged ≥70 years were attributed to macrocytic anemia. CONCLUSION: The distribution of Hb levels and the prevalence of anemia overall and by severity differ according to sex, age group, and region throughout Korea.

Does serum gastric parietal cell antibody titer have influence on anemia and vitamin B12 deficiency in atrophic glossitis patients?

BACKGROUND/PURPOSE: Our previous study found 284 gastric parietal cell antibody (GPCA)-positive atrophic glossitis (AG) patients (so-called GPCA+AG patients in this study) in a group of 1064 AG patients. This study evaluated whether high-titer (GPCA titer ≥ 160) GPCA+AG patients had greater frequencies of anemia, vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer (GPCA titer < 160) GPCA+AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 117 high-titer GPCA+AG patients, 167 low-titer GPCA+AG patients, and 532 healthy control subjects were measured and compared. RESULTS: We found that 12.0%, 29.1%, 23.1%, 16.2%, 1.7%, and 23.1% of 117 high-titer GPCA+AG patients and 5.4%, 17.4%, 17.4%, 7.2%, 1.2%, and 14.4% of 167 low-titer GPCA+AG patients were diagnosed as having macrocytosis, blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia, respectively. Moreover, both 117 high-titer and 167 low-titer GPCA+AG patients had significantly greater frequencies of macrocytosis, blood hemoglobin, serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 532 healthy control subjects (all P-values < 0.05). In addition, 117 high-titer GPCA+AG patients also had greater frequencies of anemia (P = 0.029, statistically significant), serum vitamin B12 deficiency (P = 0.027, statistically significant), macrocytosis (P = 0.075, marginal significance), and hyperhomocysteinemia (P = 0.085, marginal significance) than 167 low-titer GPCA+AG patients. CONCLUSION: For GPCA+AG patients, high-titer GPCA+AG patients have greater frequencies of anemia, serum vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer GPCA+AG patients.

Progressive myeloneuropathy with symptomatic anaemia.

Hypocupremia is a rare and under-recognised cause of bone marrow dysplasia and myeloneuropathy. A 47-year-old Caucasian woman had progressive ascending peripheral neuropathy and gait ataxia over 3 months and fatigue, dyspnoea and unintentional weight loss over 8 months. She had profound macrocytic anaemia and neutropenia. Initial workup included normal serum vitamin B12 Bone marrow biopsy was suggestive of copper deficiency. Serum copper levels were later confirmed to be undetectable. The patient received oral copper repletion which resulted in complete normalisation of haematological abnormalities 16 weeks later. However, neurological deficits persisted. This case describes a delayed diagnosis of hypocupremia as initially suggested through invasive testing. Associating myeloneuropathy with cytopenia is imperative for accurate and prompt diagnosis of hypocupremia, which can be confirmed by serum analysis alone. Developing an accurate differential diagnosis can help prevent unnecessary procedures. Furthermore, initiating prompt copper repletion prevents further neurological impairment. Neurological deficits are often irreversible.

Etiological spectrum of anemia in non-dialysis-dependent chronic kidney disease: A single-center study from India.

A retrospective study was conducted over seven years and it aimed to find out various causes of anemia among patients with chronic kidney disease (CKD). The study included nondialysis-dependent adult CKD patients who underwent anemia evaluation. A total of 584 patients were studied. Three hundred and twenty-one (55%) patients were male and 263 (45%) were female. The mean age of the patients was 55.5 ± 14 years. One hundred and seventy-eight (30.5%) had a diabetic CKD and 406 (69.5%) had a nondiabetic CKD. Seventy-two (12.3%) patients were in CKD Stage 3, 193 (33%) patients in CKD Stage 4, and 319 (54.6%) patients in CKD Stage 5. The mean hemoglobin was 9.2 ± 2.2 g/dL. There was a progressive fall in hemoglobin with increasing severity of CKD and in CKD Stage 3, 4, and 5 the mean hemoglobin was 10 ± 2.2, 9.4 ± 2.1, and 8.4 ± 1.9 g/dL, respectively (P = 0.001). Most (47.4%) patients had moderate anemia followed by anemia of mild (31.4%) and severe (21.4%) degrees. Three hundred and seven (52.6%) patients had percent transferrin saturation (TSAT) <20% (functional iron deficiency). One hundred and sixty-two (27.7%) patients had serum ferritin <100 ng/mL (absolute iron deficiency); 334 (57.2%) patients had serum ferritin 100-500 ng/mL, but in 175 (52.4%) of them, TSAT was <20%; 88 (15.1%) patients had serum ferritin >500 ng/mL (58 (65.6%) were C-reactive protein (CRP) + and 55 (62.5%) had TSAT <20%). Overall, 392 (67.1%) patients had functional or absolute iron deficiency. One-third of the patients had elevated CRP levels. The anemia was macrocytic in 20.4% suggesting deficiency of folic acid and/or Vitamin B12. A high proportion (74.6%) of patients with normocytic anemia had iron deficiency. In the majority of nondialysis-dependent CKD patients, the etiology of anemia may be multifactorial; therefore, the treatment should be determined by documented causes of anemia.

Hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with macrocytosis.

BACKGROUND/PURPOSE: Macrocytosis is defined as having the mean corpuscular volume (MCV) â‰§ 100 fL. This study evaluated whether 41 atrophic glossitis (AG) patients with macrocytosis had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects or 1064 AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 41 AG patients with macrocytosis, 1064 AG patients, and 532 healthy control subjects were measured and compared. RESULTS: We found that 73.2%, 22.0%, 73.2%, 4.9%, 80.5%, and 56.1% of 41 AG patients with macrocytosis were diagnosed as having blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 41 AG patients with macrocytosis had significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects or 1064 AG patients (all P-values < 0.001). In addition, 41 AG patients with macrocytosis also had significantly higher frequencies of serum iron and folic acid deficiencies than 532 healthy control subjects (both P-values < 0.001). Pernicious anemia was found in 22 AG patients with macrocytosis. CONCLUSION: There are significantly higher frequencies of anemia and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with macrocytosis than in healthy control subjects. AG patients with macrocytosis also have significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than AG patients.

ZRSR2 mutation in a child with refractory macrocytic anemia and Down Syndrome.

Here we report a case of refractory macrocytic anemia with a spliceosomal point mutation involving the ZRSR2 gene in a child with Down syndrome (DS). Such mutations have been shown to cause refractory macrocytic anemia and myelodysplastic syndrome (MDS) in elderly individuals. We report the hematological indices of a child with DS and a ZRSR2 spliceosomal mutation. DS is known to produce macrocytic anemia but does not lead to transfusion dependence. In this case, the ZRSR2 mutation was the likely implicating factor for severe transfusion-dependent anemia in a child with DS. The clinical implication of a ZRSR2 mutation in a child with DS has not been previously described and warrants close surveillance to detect potential insidious transformation to MDS.

Anaemia and Its Relation to Demographic, Socio-economic and Anthropometric Factors in Rural Primary School Children in Hai Phong City, Vietnam.

Little is known about the prevalence of anaemia and associated factors in school children in Vietnam. In this cross-sectional study, we aimed to determine the prevalence of anaemia and its subtypes, and the associations of types of anaemia with demographic, socio-economic and anthropometric factors among 6-9-year-old primary school children in rural areas of Hai Phong City, Vietnam. Haemoglobin (Hb) and mean corpuscular volume (MCV) were measured, and demographic, socio-economic and anthropometric data were collected in 893 children from eight primary schools. The prevalence of anaemia (Hb < 115 g/L) was 12.9% (95% CI: 8.1%, 19.9%), microcytic anaemia (Hb < 115 g/L and MCV < 80 fL) was 7.9% (95% CI: 5.3%, 11.6%) and normocytic anaemia (Hb < 115 g/L and MCV 80-90 fL) was 5.3% (95% CI: 2.9%, 9.5%). No child presented with macrocytic anaemia (Hb < 115 g/L and MCV > 90 fL). Children who were underweight, wasted, or in anthropometric failure (either underweight, stunted or wasted) were more likely to be anaemic (all p ≤ 0.004), and specifically, to have normocytic anaemia (all p ≤ 0.006), than those who were not underweight, wasted or in anthropometric failure. Stunted children were more likely to be anaemic (p = 0.018) than those who were not stunted. Overweight/obese children were less likely to be anaemic (p = 0.026) or have normocytic anaemia (p = 0.038) compared with children who were not overweight/obese. No anthropometric status indicator was associated with the risk of microcytic anaemia. No demographic or socio-economic factor was associated with any type of anaemia. Anaemia remains a public health issue in rural areas in Hai Phong City, Vietnam, and future approaches for its prevention and control should target undernourished primary school children.

Prevalence of potential underlying aetiology of macrocytic anaemia in Dutch general practice.

BACKGROUND: Macrocytic anaemia (MCV ≥ 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated. METHODS: Between the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results. RESULTS: Of the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001). Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes. CONCLUSION: In addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice.

Causes of macrocytic anemia among 628 patients: mean corpuscular volumes of 114 and 130 fL as critical markers for categorization.

There have been no studies on the distribution of causes of macrocytic anemia with respect to mean corpuscular volume (MCV) cutoff values. We retrospectively investigated the causes of macrocytic anemia (MCV ≥100 fL) among 628 patients who visited the outpatient hematology clinic in Tohoku University Hospital. To ensure data validity, we also analyzed data from 307 patients in eight other hospitals in the Tohoku district. The leading causes of macrocytic anemia (number of patients, %) were myelodysplastic syndromes (121, 19.3 %), suspected bone marrow failure syndromes (BMF; 74, 11.8 %), aplastic anemia (51, 8.1 %), plasma cell dyscrasia (45, 7.2 %), and vitamin B12 deficiency (40, 6.4 %) in Tohoku University Hospital. We made three primary findings as follows. First, the most common cause of macrocytic anemia is BMF. Second, lymphoid and solid malignancies are also common causes of macrocytosis. Third, macrocytic anemia may be classified into three groups: Group 1 (megaloblastic anemia and medications), which can exceed MCV 130 fL; Group 2 (alcoholism/liver disease, BMF, myeloid malignancy, and hemolytic anemia), which can exceed MCV 114 fL; and Group 3 (lymphoid malignancy, chronic renal failure, hypothyroidism, and solid tumors), which does not exceed MCV 114 fL. These conclusions were supported by the results from eight other hospitals.

A Zebrafish Model of 5q-Syndrome Using CRISPR/Cas9 Targeting RPS14 Reveals a p53-Independent and p53-Dependent Mechanism of Erythroid Failure.

5q-syndrome is a distinct form of myelodysplastic syndrome (MDS) where a deletion on chromosome 5 is the underlying cause. MDS is characterized by bone marrow failures, including macrocytic anemia. Genetic mapping and studies using various models support the notion that ribosomal protein S14 (RPS14) is the candidate gene for the erythroid failure. Targeted disruption of RPS14 causes an increase in p53 activity and p53-mediated apoptosis, similar to what is observed with other ribosomal proteins. However, due to the higher risk for cancer development in patients with ribosome deficiency, targeting the p53 pathway is not a viable treatment option. To better understand the pathology of RPS14 deficiency in 5q-deletion, we generated a zebrafish model harboring a mutation in the RPS14 gene. This model mirrors the anemic phenotype seen in 5q-syndrome. Moreover, the anemia is due to a late-stage erythropoietic defect, where the erythropoietic defect is initially p53-independent and then becomes p53-dependent. Finally, we demonstrate the versatility of this model to test various pharmacological agents, such as RAP-011, L-leucine, and dexamethasone in order to identify molecules that can reverse the anemic phenotype.

Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease.

BACKGROUND: Serum free light chain (FLC) analysis with ratio and urine immunofixation electrophoresis (IFE) are both available for routine use in helping to detect plasma cell dyscrasia and related diseases. CASES: Case reports showing one serum positive for serum FLC but that showed a hook effect and overestimated the amount of monoclonal FLC while urine IFE was negative for Bence Jones protein, and a second serum that showed elevated FLC κ and λ but a normal κ/λ ratio, while urine IFE was positive for Bence Jones protein. CONCLUSIONS: These two techniques complement one another. Neither of the techniques is truly quantitative, and both exhibit methodological defects.

Association of acquired thrombotic thrombocytopaenic purpura in a patient with pernicious anaemia.

Pernicious anaemia is an autoimmune disease caused by intrinsic factor antibody; it leads to vitamin B12 deficiency and is marked by ineffective erythropoiesis. Haematological features reveal macrocytosis, hyperchromasia and hypersegmented neutrophils. Schistocytes are typically seen in microangiopathy, such as in thrombotic thrombocytopaenic purpura (TTP)/haemolytic uraemic syndrome or disseminated intravascular haemolysis (DIC). We report a case of a patient with severe anaemia who presented to the emergency room. Peripheral smear revealed macrocytosis, hypersegmented neutrophils and marked schistocytosis. The patient also had high reticulocyte count with high serum lactate dehydrogenase, elevated D-dimer, low fibrinogen and low haptoglobin. Vitamin B12 level came back low and the presence of intrinsic factor antibody confirmed pernicious anaemia. ADAMTS13 level was noted to be mildly reduced, which raised the suspicion of the association of acquired TTP with pernicious anaemia. Acquired TTP is another autoimmune disorder and its association with pernicious anaemia needs further evaluation.