BACKGROUND: Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed.
METHODS: Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia.
CONCLUSIONS: This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.

Subacute combined degeneration of the spinal cord (SCD) is mainly caused by deficiency of Vitamin B12 and characterized by deep hypoesthesia, sensory ataxia and spasmodic paralysis of lower limbs. SCD often accompanies with megaloblastic anemia. Psychiatric symptoms could be the initial manifestations of SCD by lack of Vitamin B12, but are rarely considered secondary to physical discomfort and psychological factors in SCD. Additionally, treatment experience for psychiatric symptoms in SCD remains little reported.
We presented a case of a 37-year-old female who complained of being persecuted and controlled for one week and thus was admitted to the psychiatry department. Before that, she had went through persistent paresthesia and numbness of her lower extremities for two-month. Low Vitamin B12 level and hemoglobin concentration, neurologic symptoms and bone marrow smear results supported the clinical diagnosis of SCD and megaloblastic anemia. With supplementation of Vitamin B12 and blood transfusion and short-term prescription of antipsychotics and antidepressants, physical symptoms were improved and psychological symptoms disappeared within 2 weeks.
Psychiatric symptoms of SCD could be generated from lack of Vitamin B12, anemia and neurologic symptoms, where short-term use of antipsychotics and antidepressants may be effective.

Transcobalamin (TC) deficiency is a rare autosomal recessive disease characterized by megaloblastic anemia. It is caused by cellular vitamin B12 depletion, which subsequently results in elevated levels of homocysteine and methylmalonic acid. This disease is usually diagnosed by genetic analysis of the TCN2 gene. Here, we described a 2.2-month-old Chinese girl with TC deficiency presenting with diarrhea, fever and poor feeding. Whole-exome sequencing detected a pair of compound-heterozygous mutations in TCN2 gene, c.754-12C>G and c.1031_1032delGA (p.R344Tfs*20). To our knowledge, it is the first time that they were identified and reported in TC deficiency. This study contributes to a better understanding of the TC deficiency, expanding the spectrum of TCN2 mutations in this disorder and also supporting the early diagnosis and proper treatment of similar cases in the future.

There are many causes of anemia. It is unreasonable to simply associate anemia with asymptomatic ulcers in the small intestine.

BACKGROUND: Aplastic anemia (AA), megaloblastic anemia (MA), and myelodysplastic syndrome (MDS) were common anemic diseases. Sometimes it was difficult to distinguish patients with these diseases.
METHODS: In this article, we proposed one measurement method for the area of red blood cells (RBCs) from microscopic images based on image processing technology and analyzed the differences of the area in 25 patients with AA, 64 patients with MA, and 68 patients with MDS.
RESULTS: The area of RBCs was 44.19 ± 3.88, 42.09 ± 5.35, 52.87 ± 7.68, and 45.75 ± 8.07 μm2 in normal subjects, patients with AA, MA, and MDS, respectively. The coefficients of variation were 8.78%, 10.05%, 14.53%, and 14.00%, respectively, in these groups. The area of RBCs in patients with MA was significantly higher than normal subjects (p < 0.001). Compared with patients with AA and MDS, the area of RBCs in patients with MA was also significantly higher (p < 0.001). The results of correlation analysis between the area of RBCs and mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC), and red cell distribution width showed no significant correlations (p > 0.05). The area under the curve (AUC) results of the Receiver Operating Characteristic (ROC) curves of RBCs area were 0.421, 0.580, and 0.850, respectively, in patients with AA (p = 0.337), MDS (p = 0.237), and MA (p < 0.001).
CONCLUSIONS: Identifying the area of RBCs in peripheral blood smears based on the image processing technology could achieve rapid and efficient diagnostic support for patients with MDS and MA, especially for patients with MA and in combination with MCV. However, a larger sample study is needed to find the cutoff area values.

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暂无摘要。

Megaloblastic anemia (MA) patients often exhibit hemolysis, but it is not clear whether there are other hemolytic mechanisms in addition to intramedullary hemolysis. We retrospectively analyzed the clinical characteristics of 124 MA patients, measured erythrocyte physical parameters in two patients with hemolysis and one healthy volunteer by atomic force microscopy, and measured 18F-FDG uptake in one MA patient with hemolysis. In multivariate analysis, hemolysis was associated with mean corpuscular volume (MCV) and indirect bilirubin. A receiver operating characteristic curve analysis, with sensitivity of 83.1% and specificity of 68.7%, suggested that the MCV cutoff value that predicts hemolysis is 116.4 fL. Hb was negatively correlated with MCV in the hemolysis group (r = -0.317, P = 0.007) but not in the nonhemolysis group. The erythrocyte peak-valley value, average cell surface roughness and surface area in the MA patients with hemolysis were significantly lower than those in controls (P < 0.05). 18F-FDG uptake by the liver and spleen was diffuse and increased in MA patients undergoing hemolysis. MA combined with extramedullary hemolysis could be caused by macrophages removing mechanically damaged erythrocytes and the retention of erythrocytes with decreased deformability when blood circulates through narrow spaces in the liver and spleen.

暂无摘要。

Hereditary intrinsic factor deficiency is a rare disease characterized by cobalamin deficiency with the lack of gastric intrinsic factor because of gastric intrinsic factor (GIF) mutations. Patients usually present with cobalamin deficiency without gastroscopy abnormality and intrinsic factor antibodies.
A Chinese patient presented with recurrent severe anemia since age 2 with low cobalamin level and a mild elevation of indirect bilirubin. The hemoglobin level normalized each time after intramuscular vitamin B12 injection. Gene test verified a c.776delA frame shift mutation in exon 6 combined with c.585C > A nonsense early termination mutation in exon 5 of GIF which result in the dysfunction of gastric intrinsic factor protein. The hereditary intrinsic factor deficiency in literature was further reviewed and the ancestry of different mutation sites were discussed.
A novel compound heterozygous mutation of GIF in a Chinese patient of hereditary intrinsic factor deficiency was reported. It was the first identified mutation of GIF in East-Asia and may indicate a new ancestry.