OBJECTIVETo investigate the clinical significance of bone marrow morphological differences in the differential diagnosis of megaloblastic anemia (MM) and refractory anemia (R4).

METHODSA total of 60 anemia patients selected from our hospital between April 2004 and April 2015 were divided into MA group (30 cases) and RA group (30 cases) in accordance with their clinical diagnosis. Clinical manifestations, results of bone marrow morphology test, blood examination, peripheral blood smear, erythroid megaloblastic variability rate and nucleated red blood cell level in the 2 groups were compared and analyzed.

RESULTSIncidence of fever, hemorrhage, digestive reaction, splenomegaly and fatigue as well as hemoglobin level, platelets and white blood cell counts in patients of MA group were similar to those of RA group, there was no statistically significant difference between 2 groups (P>0.05). The percentages of dysplastic hematopoiesis in erythroid cells, granulocytic cells, magakaryoajtic cells, the PAS-positive rate and red blood cell distribution in the MA patients were obviously lower than those in the RA patients, while the erythroid megaloblastic variability rate (90%) in MA group was obviously higher than that in RA patients (10%) and with statistically significant difference (P<0.05). The percentage of immature red blood cells was similar between MA group (53.33%) and RA group (60.00%), without significant difference (P>0.05).

CONCLUSIONMost of clinical manifestations and peripheral blood smear results are consistent in MA patients and RA patients, bone marrow morphology detection in RA group should be focused on lymphocytoid micromegakaryocytes, while the erythroid megaloblastic cell body is the focus in MA group, PAS can be used as a diagnostic criteria.

Anemia, Megaloblastic ; diagnosis ; Anemia, Refractory ; diagnosis ; Bone Marrow ; pathology ; Diagnosis, Differential ; Erythrocyte Count ; Humans ; Leukocyte Count ; Megakaryocytes ; cytology

OBJECTIVETo evaluate the value of mean corpuscular volume/RBC distribution width (MCV/RDW) combined with reticulocyte parameters in differential diagnosis of aplastic anemia (AA), myelodysplastic syndrome (MDS), megaloblastic anemia (MA) and hemolytic anemia (HA) in order to provide some laboratorial evidence for clinical doctors in first diagnosis of these diseases.

METHODSThe data of MCV/RDW and reticulocyte parameters of AA, MDS, MA and HA patients from January 1 of 2011 to August 31 of 2014 were retrospectively collected in West China Hospital of Sichuan University. And 158 healthy unrelated individuals with age-, sex-matched were collected as controls. The value of MCV/RDW and reticulocyte parameters in differentiating diagnosis of above mentioned 4 kinds of anemia diseases was assessed. ROC analysis was used to determine the cutoff value of MCV/RDW and the reticulocyte parameters were performed in differentiating diagnosis of AA and MDS.

RESULTSThe average values of MCV/RDW of 158 AA patients (79 acute AA patients and 79 chronic AA patients), 107 MDS patients, 13 MA patients and 81 HA patients increased in variable degrees as compared with the controls, and there was statistical difference between them, the MCV/RDW value of acute AA patients was obviously less than that of other patients. In the 4 kinds of anemia diseases, the reticulocyte absolute count in acute AA patients was the lowest, that of chronic AA, MA and MDS patients was higher, and that of HA patients was highest. The ratio of low fluorescent reticulocyte decreased, and the ratio of moderate and high fluorescent reticulocytes increased in the 4 kinds of anemia diseases, as compared to controls. The difference was statistically significant. The analysis of differential diagnosis of chronic AA and MDS showed that RDW-SD could differentiate the chronic AA from MDS. The area under the curve (AUC) of RDW-SD was 0.76 (P < 0.01). The cutoff value of RDW-SD was 22.75fl. The sensitivity and specificity of RDW-SD for differential of chronic AA and MDS was 49.5% and 98.7%, respectively.

CONCLUSIONMCV/RDW and reticulocyte parameters can be used as the laboratorial differential diagnostic indicators for AA, MDS, MA and HA diseases.

Anemia, Aplastic ; Anemia, Hemolytic ; Anemia, Megaloblastic ; China ; Diagnosis, Differential ; Erythrocyte Indices ; Humans ; Myelodysplastic Syndromes ; Reticulocyte Count ; Reticulocytes ; Retrospective Studies

This study was aimed to explore the change characteristics of cell differentiation antigen (CD) on bone marrow (BM) granulocytes in patients,with megaloblastic anemia (MA). In combination with BM cell morphology, hemogram, level of blood serum folic acid, level of Vit B(12), cell genetics and biological examination data, the BM granulocytes differentiation antigens in 13 patients with MA were detected by flow cyto metry and analyzed retrospectively, in order to summarize the variation characteristics of CD13, CD33 and CD15 expressed on myeloid cells in patient with MA, including forward scatter light (FSC) and side scatter light (SSC) signal intensity, then these findings were compared with that in normal healthy persons. The results showed that the expression rates of CD13, CD15 and CD33 on granulocytic in patients with MA and normal healthy persons were (44.53 ± 16)%, (96.16 ± 2.67)%, (80.81 ± 14.71)% and (62.33 ± 11.02)%, (99.53 ± 0.46)%, (70.00 ± 7.81)% respectively, in which the expression rate of CD13 and CD15 in patients with MA decreased (P < 0.01), while the expression rate of CD33 increased (P < 0.01). The mean fluorescence intensity (MFI) of CD13, CD15, CD33, SSC and FSC in MA patients and normal healthy persons were 3.39 ± 1.41, 14.29 ± 6.59, 1.95 ± 0.94, 478.78 ± 70.43, 633.46 ± 75.53 and 5.12 ± 1.15, 20.67 ± 5.13, 1.04 ± 0.17, 332.00 ± 38.16, 537.00 ± 16.70 respectively, in which the MFI of CD13 and CD15 on granulocytes in MA patients decreased (P < 0.01),while the MFI of FSC,SSC and CD33 increased (P < 0.01 and P < 0.05). It is concluded that not only the morphology of BM granulocytes in patents with MA shows dysmaturity, but the expressing feature of differentiation antigens on BM granulocytes in MA patients also displays dysmaturity.These findings will contribute to the clinical diagnosis of MA patients.
Adult ; Aged ; Anemia, Megaloblastic ; diagnosis ; immunology ; metabolism ; Antigens, CD ; metabolism ; Case-Control Studies ; Female ; Granulocytes ; metabolism ; Humans ; Male ; Middle Aged ; Retrospective Studies

BACKGROUND: Macrocytic anemias are commonly seen in clinical practice, and precise etiologic diagnosis is essential for proper management. We evaluated the clinical utility of reticulocyte maturation parameters in macrocytic anemias to discriminate among myelodysplastic syndrome (MDS), megaloblastic anemia (MA), and non-megaloblastic macrocytic anemia associated with chronic liver disease (MA-CLD). METHODS: Using an automated reticulocyte counter, we retrospectively analyzed and compared reticulocyte maturation parameters including immature reticulocyte fraction (IRF), mean reticulocyte volume (MRV), mean sphered cell volume (MSCV) of normal control (N=34), and patients diagnosed with MDS (N=31), MA (N=52), and MA-CLD (N=196). RESULTS: Macrocytic anemias from MA, MDS and MA-CLD showed higher values of reticulocyte maturation parameters including IRF, MRV and MSCV than normal control (P<0.01). MDS showed higher values of reticulocyte maturation parameters including IRF, MRV and MSCV than MA-CLD (P<0.01). IRF and MRV were significantly lower in MA-CLD than in both MA and MDS (P<0.01). MSCV was significantly higher in MDS than in MA (P<0.01). CONCLUSIONS: This study indicates that the measurement of reticulocyte maturation parameters may be a useful tool in the differential diagnosis of macrocytic anemia. The presence of high values of IRF (> or = 0.39), MRV (> or = 129.5 fL), and MSCV (> or = 102.3 fL) makes the diagnosis of MA-CLD unlikely and underlying MDS should be considered.
Adult ; Anemia, Macrocytic/*diagnosis ; Anemia, Megaloblastic/*diagnosis ; Chronic Disease ; Diagnosis, Differential ; Female ; Humans ; Liver Diseases/*diagnosis ; Male ; Middle Aged ; Myelodysplastic Syndromes/*diagnosis ; Reticulocyte Count/*methods

Iron deficiency anemia (IDA) and megaloblastic anemia due to vitamin B12 deficiency are well-characterized prototypes of anemia. There is no doubt that IDA is the most common hematologic disorder in Korea and worldwide as well. The diagnosis and treatment of IDA is not a difficult practice usually, however, a caution is required in detecting early-stage iron deficiency and in distinguishing IDA from anemia of chronic disorders such as chronic inflammatory disease, malignancies, chronic liver disease, and chronic renal disease. Administration of a standard iron preparation at a proper dosage over an adequate period is a prerequisite for the successful treatment of IDA, which is sometimes overlooked by both physicians and patients. Early detection and treatment as well as prevention of iron deficiency per se are also required. Pernicious anemia is the most common cause of vitamin B12 deficiency in Western populations. By contrast, the disorder is rare in Korea, although the number of cases seems to be increasing these days. The majority of patients with megaloblastic anemia reveal a history of gastrectomy. Thus, it should be reminded that vitamin B12 supplementation is important to prevent the development of overt deficiency or anemia in these susceptible individuals, since a delay in the treatment of vitamin B12 deficiency may result in an irreversible neurologic deficit.
Anemia* ; Anemia, Iron-Deficiency ; Anemia, Megaloblastic ; Anemia, Pernicious ; Diagnosis ; Gastrectomy ; Humans ; Iron ; Korea ; Liver Diseases ; Neurologic Manifestations ; Renal Insufficiency, Chronic ; Vitamin B 12 ; Vitamin B 12 Deficiency

Megaloblastic anemia induced by Vitamin B12 deficiency is a disorder caused by impaired DNA synthesis. It has been previously thought to be rare in children, however, recent studies suggest that this condition is more common than previously recognized. Deficiency can lead to a wide spectrum of hematologic and neuropsychiatric disorders. Especially in children, it often presents with nonspecific manifestations, such as developmental delay, irritability, weakness, and failure to thrive. Early diagnosis and prompt treatment might resolve these complications, but permanent neurologic damage may have already occurred. We experienced two cases of Megaloblastic Anemia induced by Vitamin B12 deficiency and report them with a brief review of the literature.
Anemia, Megaloblastic* ; Child* ; DNA ; Early Diagnosis ; Failure to Thrive ; Humans ; Megaloblasts* ; Vitamin B 12 Deficiency* ; Vitamin B 12* ; Vitamins*

BACKGROUND: Methylmalonic acid (MMA) is one of the metabolites of the DNA synthesis metabolic pathway wherein vitamin B12 acts as a coenzyme. Vitamin B12 deficiency leads to inhibition of methyl-malonyl CoA mutase, and sequential elevation of blood and urine concentrations of MMA. It has been known that the urine concentration of MMA is a more specific and sensitive marker than the hema-tologic indices and the serum concentration of vitamin B12 for the diagnosis of vitamin B12 deficiency. We investigated the sensitivity of urine concentration of MMA and the usefulness as a differential mark-er for myelodysplastic syndrome (MDS) and megaloblastic anemia (MA). METHODS: We identified 37 cases that were examined for both urine concentrations of MMA and bone marrow studies from January 1996 to December 2000. Serum concentrations of vitamin B12 and folate were measured by the chemiluminescence immunoassay using ACS:180 (Bayer Diag-nostics). Urine concentration of MMA was measured by isotope dilution gas chromatography-mass spectrometry (GC 8000-gas chromatography MD800). RESULTS: Of 36 patients, 12 patients were diagnosed with MA, 8 patients with MDS, 5 patients with aplastic anemia based on the bone marrow study. Increased urine concentration of MMA was observed in all the patients with MA, but none of the patients with MDS. Using a cut-off value of 5 mmol/mol creatinine urine concentration MMA, the sensitivity and specificity in diagnosis for MA were 100% and 80%. The correlation between the urine concentration of MMA and the serum con-centration of vitamin B12 was insignificant (r=-0.25, P=0.21). The highest correlation index with urine concentration of MMA was the red cell distribution width (r=0.74, P < 0.01). CONCLUSIONS: We concluded that the urine concentration of MMA was a sensitive marker for diagno-sis of MA caused by vitamin B12 deficiency and could be a useful test in the differentiation for MA from MDS. Although a consensus for a diagnostic value of the urine concentration of MMA would be nec-essary, we recommend using both the urine concentration of MMA and the serum vitamin B12 as prima-ry tests for diagnosis of MA caused by vitamin B12 deficiency.
Anemia, Aplastic ; Anemia, Megaloblastic* ; Bone Marrow ; Chromatography ; Consensus ; Creatinine ; Diagnosis ; DNA ; Erythrocyte Indices ; Folic Acid ; Gas Chromatography-Mass Spectrometry ; Humans ; Immunoassay ; Luminescence ; Megaloblasts* ; Metabolic Networks and Pathways ; Methylmalonic Acid* ; Myelodysplastic Syndromes ; Sensitivity and Specificity ; Vitamin B 12 Deficiency* ; Vitamin B 12* ; Vitamins*

Methotrexate is a very potent inhibitor of dihydrofolate reductase and causes bone marrow suppression and megaloblastic anemia. It is widely used in combination with other chemotherapeutic agents in lymphoproliferative disorders. A 63 year old man with ischioneuralgia developed exertional dyspnea and dizziness after he had intentionally taken methotrexate in doses of 5mg per day for 2months. Five months after discontinuation of methotrexate, his bone marrow showed the hypercellular marrow with 90% cellularity, 15% blasts and marked dysgranulopoiesis, suggestive of refractory anemia with excess blasts(RAEB). The hematopoietic cells were not enough aspirated for proper diagnosis in follow up bone marrow after three months. The bone marrow aspirates showed 13% blasts, and marked dysgranulopoiesis. The bone marrow biopsy showed hypercellular marrow with 100% cellularity, but marked fibrosis was developed. The cytogenetic study revealed normal karyotype.
Anemia, Megaloblastic ; Anemia, Refractory ; Biopsy ; Bone Marrow ; Cytogenetics ; Diagnosis ; Dizziness ; Dyspnea ; Fibrosis ; Follow-Up Studies ; Humans ; Intention ; Karyotype ; Lymphoproliferative Disorders ; Methotrexate* ; Middle Aged ; Myelodysplastic Syndromes* ; Tetrahydrofolate Dehydrogenase

BACKGROUND & OBJECTIVES: Subacute combined degeneration (SCD) is a disease of spinal cord involving the posterior and lateral column due to vitamin B12 deficiency. The clinical and electrophysiologic findings of SCD are various. METHODS: From 1989 to 1996, 7 patients were diagnosed with SCD in our hospitals. The diagnosis was made by the neurologic and laboratory findings and electrophysiolgic studies such as nerve conduction studies(NCS) and evoked potential(EP). RESULT: Four patients received gastrectomy. Two had chronic atrophic, gastritis; one of them was assumed to have food-cobalamin malabsorrtion. The remaining one was a heavy drinker. The mean duration of neurologic symptoms was 35.7 months. The most common initial complaint was paresthesia (in 4) and impairment of cutaneous sensation was the most common neurologic sign At the time of diagnosis, 5 patients had myelopathy with was supported by EP in 3(60%). There were abnormal NCS findings in 5 f 6 patients with peripheral neuropathy. In one patient, there was no symptom and sign compatible with myelopathy but median nerve SEP showed bilateral central conduction delay. No one had visual symptoms but prolongation of P 100 was detected in 2 patients. Sural nerve biopsy was done in 2 case, which revealed chronic nonspecific neuropatby in one and chronic axonopathy in the other. Megaloblastic anemia was found in 4 cases and improved by cobalamin therapy in all the parents, in which the follow up hematologic data were available. There as a tendency that nonanemic patients had more severe neurologic symptoms than anemic ones. We could not find any relationship between the duration and severity of neurologic menifestations was best in the patients with the shortest duration of neurologic manifestations and hematologic feature festations. CONCLUSIONS: The authors suggest that early detection and treatment is very important for the improvement of symptoms in SCD.
Anemia, Megaloblastic ; Biopsy ; Diagnosis ; Follow-Up Studies ; Gastrectomy ; Gastritis ; Humans ; Median Nerve ; Neural Conduction ; Neurologic Manifestations ; Parents ; Paresthesia ; Peripheral Nervous System Diseases ; Sensation ; Spinal Cord ; Spinal Cord Diseases ; Subacute Combined Degeneration* ; Sural Nerve ; Vitamin B 12 ; Vitamin B 12 Deficiency

The author obtained index of red cell volume distribution width(RDW) and other red cell indices in 210 patients of various hematoncologic conditions and 200 healthy control group using, an automated blood analyzer, Coulter Counter Model S-plus II. This study performed to classify various etiologic anemia based on the MCV and RDW, to evaluate availability to the differential diagnosis in korean anemic distoders somewhat different from etiologies of anemias in foreginers. In the most of cases, the increase or decrease of MCV were always combined the pararell changes of MCH and MCHC: But the values of MCV and RDW were not correlated in control group and patient group. So the terms of heterogenous of homogenous anemia were meaningful morphologic classification than hypochromic or normochromic anemia. The heterogenous microcytic anemia contained iron deficiency anemia. In heterogenous normocytic anemia, myelophthisic anemia, acute leukemia were contained. In heterogenous macrocytic anemia, megaloblastic anemia, hemolytic anemia were contained. The homogenous microcytic anemia was observed in anemia of chronic disorders. In homogenous normocytic anemia, acute blood loss, chronic leukemia, multiple myeloma were contained. The aplastic anemia was belonged to homogenous macrocytic anemia. The diagnostic significance of RDW in hemoglobinopathies is most importhant. But this study was not contained hemoglobinopathies. Instead RDW was very helpful to differential diagnosis of most common anemias, iron deficiency anemia and anemia due to chronic disorders in Korea.
Anemia* ; Anemia, Aplastic ; Anemia, Hemolytic ; Anemia, Iron-Deficiency ; Anemia, Macrocytic ; Anemia, Megaloblastic ; Anemia, Myelophthisic ; Cell Size ; Classification* ; Diagnosis, Differential ; Erythrocyte Indices ; Hemoglobinopathies ; Humans ; Korea ; Leukemia ; Multiple Myeloma