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.

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.

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.

The impact of preoperative anaemia and anaemic subtype on patient outcome in colorectal cancer.

AIM: Preoperative anaemia is associated with adverse outcomes in colorectal cancer (CRC). To clarify the reason for this we aimed to comprehensively assess the association of preoperative anaemia with tumour characteristics, host systemic inflammation and nutrition status, and perioperative blood transfusion. METHOD: We used an integrated database of 592 CRC patients. The association of preoperative anaemic subtype, calculated from haemoglobin and erythrocyte mean corpuscular volume levels, with patient outcome, preoperative serum data relating to systemic inflammation and nutrition and perioperative blood transfusion was analysed. RESULTS: Preoperative anaemia was significantly associated with poorer overall survival and relapse-free survival (RFS); in particular microcytic anaemia had a trend to poorer RFS than other forms of anaemia (P = 0.0648). In addition, preoperative anaemia was significantly correlated with right-sided tumours, greater depth of tumour invasion, use of neoadjuvant chemotherapy, poorer prognostic nutritional index and higher modified Glasgow Prognostic Score (mGPS). Microcytic anaemia in particular had a strong association with a greater depth of tumour invasion (P = 0.0072) and higher mGPS (P = 0.0058) than other causes of anaemia. Perioperative blood transfusion for CRC patients with anaemia was associated with adverse outcomes. CONCLUSIONS: Preoperative anaemia, especially microcytic anaemia, was associated with poor patient outcomes, possibly due to poor systemic inflammatory and nutritional status, and it was not improved by perioperative blood transfusion. Our data suggest that preoperative anaemia and the anaemic subtype may serve as an easily available predictor of outcome in CRC.

Anemia and hematinic deficiencies in anti-gastric parietal cell antibody-positive or all autoantibodies-negative recurrent aphthous stomatitis patients.

BACKGROUND/PURPOSE: Approximately 13% of recurrent aphthous stomatitis (RAS) patients have serum anti-gastric parietal cell antibody (GPCA) positivity. This study assessed whether serum GPCA or RAS itself was a significant factor causing hematinic deficiencies and anemia statuses in GPCA-positive RAS (GPCA+/RAS) and all autoantibodies-negative RAS (Abs-/RAS) patients. METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of three groups of 31 GPCA+/RAS patients, 240 Abs-/RAS patients, and 342 healthy control subjects. RESULTS: GPCA+/RAS patients had significantly lower mean Hb and serum iron level (for women only) as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy control subjects. Moreover, GPCA+/RAS patients had a significantly higher MCV and a significantly greater frequency of vitamin B12 deficiency than Abs-/RAS patients. Furthermore, Abs-/RAS patients did have significantly lower mean Hb, MCV, iron, and folic acid levels and significantly greater frequencies of Hb, iron, vitamin B12, and folic acid deficiencies than healthy control subjects. Of 31 GPCA+/RAS patients, 3 (9.7%) had PA, 6 (19.4%) had vitamin B12 deficiency, and 3 (9.7%) had macrocytosis. Moreover, normocytic anemia (54.0%) and iron deficiency anemia (26.4%) are the two more common types of anemia in our RAS patients. CONCLUSIONS: We conclude that serum GPCA plays a significant role in causing vitamin B12 deficiency and high MCV in GPCA+/RAS patients. RAS itself does play a significant role in causing anemia and hematinic deficiencies in both GPCA+/RAS and Abs-/RAS patients.

Prevalence of anaemia among Quranic school (Khalawi) students (Heiran)in Wad El Magboul village, rural Rufaa, Gezira State, Central Sudan: a cross sectional study.

INTRODUCTION: This is a cross sectional descriptive community-based study. The aim was to assess the prevalence of anaemia among quranic schoolchildren in khalawi Wad EL Magboul village, rural Rufaa, Gezira State, central Sudan. METHODS: A sample of 180 male participants were included in the study. Informed consent was obtained. Venous blood samples were obtained to measure the hematological parameters and blood films for malaria parasites. Urine and stool analyses were also done. Data were analyzed using SPSS. RESULTS: The mean age of participants was 12.31 years (SD +/- 2.26). The mean Hb value was 11.75g/dl and it was statistically significant correlation when compared with the mean Hb reference value (13.5g/dl) P value 0,000 (95% CI). Regarding period of stay in the khalwa up to the time of the study, 88 (49.28%) for one year, 54 (30.24%) for 2 years, 22 (12.32%) for 3 years and 16 (8.96%) for more than 3 years. About 77 students (42.78%) were pale on clinical examination. The Mean Cell Hemoglobin (MCH) mean value was 25.58 pg ( 3.55). Many conditions known to be associated with anemia were found; 49 students (27.2%) had a positive blood films for falciparum malaria, 14 students (7.8%) were found to have haematuria and ova of S. haematobium, In169 students (93.4%) stool examination was negative , while 11 students (6.6%) had intestinal worms (Enterobius vermicularis). CONCLUSION: Majority of the study participants had iron deficiency anaemia, followed by haemolytic, macrocytic and sickle cell anaemia. This might have negative health and educational implications.

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.

Prior cytopenia predicts worse clinical outcome in acute myeloid leukemia.

The prognosis of acute myeloid leukemia (AML) is influenced by both disease-intrinsic and patient-related factors. In particular, AML following myelodysplastic syndrome (MDS) (AML with myelodysplasia-related changes, AML-MRC) has a poor prognosis. We hypothesized that patients with cytopenias prior to AML, but no known prior MDS, may share biologic features with AML-MRC. We evaluated 140 AML patients without prior MDS who had complete blood count (CBC) data available 6-36 months prior to their diagnosis. Cytopenia, defined as clinically unexplained thrombocytopenia or macrocytic anemia, was present in 29/140 (21%) patients. Compared to non-cytopenic patients, AML patients with prior cytopenia were older and more often met morphologic or cytogenetic criteria for AML-MRC. Prior cytopenia was associated with shorter survival in patients with intermediate-risk cytogenetics (median OS 4.2 versus 24.1 months, p<0.0001), but not in patients with adverse-risk cytogenetics (median OS 4.4 versus 6.0 months, p=0.57). Prior thrombocytopenia, but not macrocytic anemia, was significantly associated with shorter overall survival (p=0.01) independent of treatment approach, karyotype risk, and age on multivariable analysis. Our data suggest that AML patients with prior cytopenias have features similar to AML-MRC, and in particular support the use of prior unexplained thrombocytopenia as an independent marker of high-risk disease.

[Clinical, biological and therapeutic profile of anemia by vitamin B12 deficiency in the department of hematology of Marrakech (Morocco)]. / Profil clinique, biologique, et thérapeutique de l'anémie par carence en vitamine B12 dans le service d'hématologie de Marrakech (Maroc).

The aim of this study is to examine retrospectively the clinical, biological and treatment features of anemia by vitamin B12 deficiency in the Hematology department of CHU Mohamed VI Marrakech. We report the results of a retrospective study conducted during six years (2005-2010). It included all patients with anemia (with or without thrombocytopenia or leukopenia) associated with vitamin B12 levels <200 pg / ml. One hundred twenty one cases were analyzed. The average age of patients was 62 years (38-89 years) with a female predominance (sex ratio F/M: 1.3). The clinical symptomatology is dominated by pallor (97.5%), cardiovascular signs (46%) and digestive symptoms (34.7%). Neurological signs were noted in 17.3% of cases. The blood count showed anemia (hemoglobin: mean= 6.9 g/dl), macrocythemia (MCV: mean= 109 fl). Leukopenia was noted in 35 patients (29%), thrombocytopenia in 34 patients (28%) and pancytopenia in 21 patients (17,3%). The average vitamin B12 was 72 pg/ml. The causes of B12 deficiency are pernicious anemia (43%), food-cobalamin malabsorption (43%), and in 14% of cases no etiology was found. Gastritis was found in 82.7% of our patients and Helicobacter pylori (HP) infection in 72.7% of cases. Reticulocyte crisis was observed after parenteral administration of hydroxocobalamine within an average of 8 days and normalization of blood counts, in all patients, within an average of 51 days. In patients with HP infection, eradication therapy of HP was performed. The cure rate of the HP is 90%.

Prevalence and incidence of anemia in the German Heinz Nixdorf Recall Study.

This study aims to determine prevalence and incidence of anemia in the general population in Germany and evaluate a potential role of serum-free light chains (FLC) as biomarker in anemia. The population-based Heinz Nixdorf Recall Study comprises 4,814 men and women aged 45-75 years. Hemoglobin <13 g/dl in men and <12 g/dl in women defined anemia. Laboratory data was used to classify cases into renal, iron deficiency (IDA), vitamin B12/folic acid deficiency, anemia of chronic disease (ACD), and unexplained anemia (UA). Follow-up data was available from annual questionnaires, death certificates, and 5-year follow-up visit (5-year FU). Anemia cases (152) were identified (prevalence 3.2 %, 95 % CI 2.7-3.7). In participants aged 65 or older, prevalence was 4.3 % (95 % CI 2.9-6.0) in both men and women. Main anemia subtypes were: IDA 19 %, ACD 25 %, and UA 44 %. Incidence increased with age and was 12.8/1,000 person-years and 10.9/1,000 person-years in men and women aged 65 or older, respectively. UA was characterized by elevated FLC. Participants with elevated FLC and high-sensitivity C-reactive protein (hsCRP) had an increased risk of anemia at 5-year FU. FLC-alone or in combination with hsCRP-may serve as biomarker indicating an increased risk of developing anemia.

Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited.

PURPOSE: Interstitial deletions of chromosome 5q are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the pathogenic role of this region in disease phenotype and clonal evolution. The higher level of resolution of single-nucleotide polymorphism array (SNP-A) karyotyping may be used to find cryptic abnormalities and to precisely define the topographic features of the genomic lesions, allowing for more accurate clinical correlations. PATIENTS AND METHODS: We analyzed high-density SNP-A karyotyping at diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant myeloid disorders. results: We identified chromosome 5q deletions in 142 (12%) of 1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155 patients. Patients with deletions involving the centromeric and telomeric extremes of 5q have a more aggressive disease phenotype and additional chromosomal lesions. Lesions not involving the centromeric or telomeric extremes of 5q are not exclusive to 5q- syndrome but can be associated with other less aggressive forms of MDS. In addition, larger 5q deletions are associated with either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a deletion involving the centromeric and/or telomeric regions or heterozygous mutations in NPM1 or MAML1 located in 5q35 were present. CONCLUSION: Our results suggest that the extent of the affected region on 5q determines clinical characteristics that can be further modified by heterozygous mutations present in the telomeric extreme.

[Hyperhomocysteinemia and leg ulcers: A prospective study of 68 patients]. / Hyperhomocystéinémie et ulcères de jambes : étude prospective de 68 observations.

BACKGROUND: Homocysteine is a sulphur-containing amino acid derived from methionine. Hyperhomocysteinaemia is now recognised as an independent risk factor for occlusive arterial disease and thrombotic venous disease. The aim of this study was to determine the prevalence of hyperhomocysteinemia in patients with leg ulcers. PATIENTS AND METHODS: We prospectively investigated hospitalised patients for vascular leg ulcers between March 2008 and June 2009 at two dermatology centres. We collected details of cardiovascular disease and determined nutritional status by means of the MNA score. Fasting blood samples were taken and analyzed for homocysteine, albumin, prealbumin, folic acid, vitamin B12, creatinine and a complete blood count. RESULTS: Sixty-eight patients were enrolled in the study: 48 women and 20 men. Fifty-three percent of patients had venous leg ulcers, 18% had arterial leg ulcers and 20% had leg ulcers of mixed origin. The prevalence of hyperhomocysteinemia was 56%, with no differences according to ulcer type or gender. DISCUSSION: While the prevalence of hyperhomocysteinemia in our population of leg ulcer patients was high, this descriptive study does not allow us to establish any causal link between hyperhomocysteinemia and leg ulcers. Moreover, since the literature indicates that homocysteine-lowering therapy does not reduce cardiovascular and thromboembolic risk, there appears to be little call for further trials on hyperhomocysteinaemia and leg ulcers.

Estudio de macrocitosis sin anemia en una población urbana / Macrocytosis without anaemia in an urban population

Objetivo: Describir las situaciones relacionadas con la macrocitosis sin anemia en nuestrapoblación, entendida esta como un volumen corpuscular medio (VCM) mayor o igual a 97 fl ycifras de hemoglobina dentro de los límites normales poblacionales. Si descartadas las principalescausas recogidas en la literatura médica no existe justificación clara para esta macrocitosis,debe realizarse un test del aliento para valorar la posible asociación del aumento del VCM conla presencia de infección por Helicobacter pylori.Dise˜no: Transversal y descriptivo.Emplazamiento: Atención primaria.Mediciones principales: Las variables medidas fueron datos de filiación, antecedentes personalesy analíticos relacionados con la macrocitosis, consumo de tóxicos y fármacos. Todos estosdatos se recogieron de la historia clínica.Resultados: La prevalencia de macrocitosis sin anemia en la población de estudio fue de un7,12% (1.403/19.710). La principal causa que se encontró fue el hipotiroidismo en 37/234pacientes (15,8%), seguido del consumo elevado de alcohol en 34/234 pacientes (14,5%). Laasociación que se dio con mayor frecuencia fue la de consumo de alcohol y tabaco en 9/234pacientes (3,8%). En 87/234 pacientes (37,18%) no se halló causa conocida aparente de elevacióndel VCM. Se realizó el test del aliento a 37 pacientes y fue positivo en 23 pacientes(AU)

Conclusiones: La macrocitosis sin anemia es un hallazgo de alta prevalencia en nuestro medio.El hipotiroidismo es la causa que se encuentra en primer lugar, por delante del alcohol, causaprincipal en la literatura médica consultada, pero también es frecuente que exista más deuna causa por paciente que pueda justificar este hallazgo. Hoy en día, el H. pylori parecerelacionado con diversas enfermedades, digestivas o no, y puede ser causa de VCM elevado sinanemia. Sin embargo, en nuestro estudio no podemos concluir este hallazgo, pero podemosconfirmar la elevada prevalencia de H. pylori en nuestro medio(AU)

Objective: Observational study on a group of patients with macrocytosis without anaemia. Theprobable relationship of cause and effect between Helicobacter pylori and macrocytosis.Methods and material: An observational and cross-sectional study.Main measurements: The measured variables were: personal data, medical and analytical historyin relation to macrocytosis, alcohol and smoking habitss and drug use. This informationwas taken from the medical history of the patient.Results: The prevalence of macrocytosis without anaemia was 7.12%. The main cause found washyphothyroidism in 37/234 (15.8%) patients, followed by alcoholism in 34/234 (14.5%) patients.The most frequent association was alcohol and tobacco in 9/234 (3.8%) patients. It was notpossible to find a cause of the increased mean corpuscular volume (MCV) in 87/234 (37.18%)patients. Out of 37 tests conducted for Helicobacter pylori, 23 of them were positive.Discussion: Macrocytosis without anaemia has a high prevalence. Finding the most frequent causescould help in the early diagnosis and treatment. H. pylori currently appears to be associatedto different digestive tract and non-digestive tract diseases.It could be a cause of increasedMCV, but this study was unable demonstrate this(AU)

Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors.

BACKGROUND: Folate deficiency has serious consequences for the fetus. Folic acid fortification of food addresses this problem. However, clinical consequences of vitamin B-12 deficiency may be worsened by high folic acid intakes, perhaps as a direct result of unmetabolized folic acid, which does not occur naturally in body tissues. OBJECTIVE: We attempted to attribute associations that we previously found between higher folate status and anemia and cognitive test performance to circulating unmetabolized folic acid or 5-methyltetrahydrofolate (5MeTHF). DESIGN: The subjects (n = 1858) were senior participants in the US National Health and Nutrition Examination Survey (1999-2002) who had normal renal function and reported no history of stroke, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries. Subjects had undergone a phlebotomy, a complete blood count, and cognitive and dietary assessments. RESULTS: Circulating unmetabolized folic acid was detected in approximately 33% of the subjects and was related to an increased odds of anemia in alcohol users. In seniors with a serum vitamin B-12 concentration <148 pmol/L or a plasma methylmalonic acid concentration > or =210 nmol/L, the presence compared with the absence of detectable circulating unmetabolized folic acid was related to lower cognitive test scores and lower mean cell volume. In the same subgroup, higher serum 5MeTHF was related to an increased odds of anemia and a marginally significantly decreased odds of macrocytosis. In seniors with a normal vitamin B-12 status, a higher serum 5MeTHF concentration was related to higher cognitive test scores. CONCLUSION: Results of this epidemiologic study were somewhat consistent with reports on the folic acid treatment of patients with pernicious anemia, but some findings were unexpected.

Tyrosine kinase inhibitor-induced macrocytosis.

BACKGROUND: The tyrosine kinase inhibitors (TKI) sunitinib and imatinib were shown to induce macrocytosis in patients with renal cell cancer (RCC) and gastrointestinal stromal tumors (GIST), presumably through inhibition of the c-KIT dependent signaling pathway of erythroid progenitor cells of the bone marrow. PATIENTS AND METHODS: Hematology charts of patients with RCC, breast cancer (BC), GIST, non-small cell lung cancer (NSCLC) and hepatocellular cancer (HCC), receiving single-agent sunitinib, imatinib, sorafenib, erlotinib and BI 2992 (Tovok) at the recommended dose for at least 3 months were reviewed retrospectively for the occurrence of macrocytosis. RESULTS: Macrocytosis occurred in all patients with RCC and BC treated with sunitinib and in all patients with GIST treated with imatinib. The percentage increase of the mean corpuscular volume (MCV) of peripheral red blood cells (RBC) compared with baseline at 3, 6, 9 and 12 months was 12.4%, 16.8%, 16.6%, 12.7% and 0.7%, 5.6%, 5.9%, 5% with sunitinib and imatinib respectively. The values at 3, 6 and 9 months between both groups were significantly different. Sorafenib, erlotinib and BI 2992 did not induce macrocytosis. CONCLUSION: Sunitinib-induced macrocytosis was not confined to patients with RCC alone but also occurred in patients with BC. Imatinib also induced macrocytosis in patients with GIST but to a significantly lower degree. Because both drugs were used at an effective pharmacodynamic dose inhibiting c-KIT, these data strongly suggest that pathways in addition to c-KIT and not common to both agents are involved in the TKI-induced macrocytosis.

Hemoglobin and hematocrit values are higher and prevalence of anemia is lower in the post-folic acid fortification period than in the pre-folic acid fortification period in US adults.

BACKGROUND: It is not known whether the improved folate status from mandatory folic acid fortification had any impact on indexes and prevalence of anemias in the United States. OBJECTIVE: We investigated trends in indexes and prevalence of anemia and macrocytosis with a focus on comparison of prefortification data with postfortification data. DESIGN: Hemoglobin, hematocrit, mean corpuscular volume (MCV) and prevalences and likelihood of anemia and macrocytosis were determined for 26,596 adults examined in the National Health and Nutrition Examination Surveys, 1988-2004. RESULTS: From 1988-1994 to 1999-2004, hemoglobin modestly but significantly improved from 15.1 to 15.4 g/dL (approximately 2.0%; P < 0.0001) and from 13.3 to 13.6 g/dL (approximately 2.3%; P < 0.0001) in men and women, respectively. There was a significant increase in MCV from 1988-1994 to 1999-2004 in men (from 90.2 to 90.7; P = 0.0123) and older (>60 y) men (from 91.6 to 92.4; P = 0.0105) and in women (from 90.7 to 91.4; P = 0.0141). Only in women was the prevalence of anemia significantly lower in 1999-2004 than in 1988-1994 (27.9% reduction; P = 0.0005). The odds of having anemia in the postfortification period relative to the prefortification period was 0.64 (95% CI: 0.54, 0.75; P < 0.0001) in women and 0.79 (95% CI: 0.62, 0.99; P < 0.0433) in men. In general, the prevalence of macrocytosis and the odds of having macrocytosis did not change significantly from 1988-1994 to 1999-2004. CONCLUSION: The improvement in hemoglobin and the decreased prevalence of anemia from 1988-1994 to 1999-2004, especially in women, may be attributable to improved folate status, increased vitamin/mineral supplements use, and other unknown causes after the initiation of folic acid fortification. The cause of increased MCV in men, and in older persons of both sexes, warrants further investigation.

Sunitinib-induced macrocytosis in patients with metastatic renal cell carcinoma.

BACKGROUND: Sunitinib and sorafenib are small molecules that inhibit the vascular endothelial growth factor and related receptors with substantial clinical activity reported in metastatic renal cell carcinoma (RCC). Cytopenia and macrocytosis have been described in patients treated with these agents. METHODS: A retrospective review of all patients with metastatic RCC who were treated with sunitinib or sorafenib for at least 3 months at the Cleveland Clinic Taussig Cancer Institute was undertaken. Complete blood count (CBC) data including red blood cell indices were recorded at baseline, after 3 months of therapy, and at the end of treatment. RESULTS: A total of 61 patients were treated with sunitinib and 37 patients were treated with sorafenib with available CBC data. In patients treated with sunitinib, the median corpuscular volume (MCV) increased significantly at 3 months compared with baseline (median increase of 5.1 femtoliters [fL]; P < .001) and continued to increase throughout treatment. Patients who developed hypothyroidism had a larger MCV increase at 3 months than patients who remained euthyroid (P = .06), although macrocytosis was observed in patients without hypothyroidism. Ten patients discontinued sunitinib therapy, and the MCV decreased in all patients within 2 to 4 months, without further intervention. Bone marrow analysis of 4 patients revealed a hypocellular bone marrow with trilineage hematopoiesis and no evidence of metastasis. There was no evidence of folate or vitamin B12 deficiency. In contrast to sunitinib, there was no change in the MCV for patients treated with sorafenib. CONCLUSIONS: Macrocytosis was a common occurrence after treatment with sunitinib but not sorafenib in patients with metastatic RCC. Sunitinib-induced macrocytosis is reversible with drug discontinuation.