Evaluation of Macrocytic Anemias

Green, Ralph; Dwyre, Denis M.

doi:10.1053/j.seminhematol.2015.06.001

Cited by 46 publications

(33 citation statements)

References 40 publications

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“…Extremely high MCV (>130 fL) narrows the differential diagnosis, to include ART treatment for HIV infection, use of hydroxyurea, and vitamin B12 or folate deficiency . The MCV values may be falsely elevated when significant reticulocytosis is present, because the reticulocyte volume is high . Moreover, hyperglycemia, marked leukocytosis, and cold agglutinins cause spurious macrocytosis …”

Section: Differential Diagnosis Of Macrocytic Anemiasmentioning

confidence: 99%

Diagnosis and treatment of macrocytic anemias in adults

Nagao

Hirokawa

2017

J of Gen and Family Med

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Anemia is one of the most common health problems in the primary care setting. Macrocytosis in adults is defined as a red blood cell (RBC) mean corpuscular volume (MCV) >100 femtoliter (fL). Macrocytic anemias are generally classified into megaloblastic or nonmegaloblastic anemia. Megaloblastic anemia is caused by deficiency or impaired utilization of vitamin B12 and/or folate, whereas nonmegaloblastic macrocytic anemia is caused by various diseases such as myelodysplastic syndrome (MDS), liver dysfunction, alcoholism, hypothyroidism, certain drugs, and by less commonly inherited disorders of DNA synthesis. Macrocytic anemias are treated with cause‐specific therapies, and it is crucial to differentiate nonmegaloblastic from megaloblastic anemia. Because MDS and myeloid neoplasms commonly affect the elderly, primary care physicians may encounter more cases of macrocytic anemias in the near future, as the older population increases. When MDS is suspected along with leukocytopenia and/or thrombocytopenia with anemia, a hematology consultation may be appropriate.

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Section: Differential Diagnosis Of Macrocytic Anemiasmentioning

confidence: 99%

Diagnosis and treatment of macrocytic anemias in adults

Nagao

Hirokawa

2017

J of Gen and Family Med

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“…Since palbociclib affects cancer cell growth/proliferation by CDK4/6 inhibition, and CDK4/6 inhibition seems to temporally correlate with change in MCV, change in MCV is a potential pharmacodynamic biomarker of functional CDK4/6 inhibition in vivo. While macrocytosis (MCV≥100 fl) has clinical significance in several hematological diseases 6 , we believe that a more important pharmacodynamic biomarker of palbociclib effect would be change in MCV, which not only accounts for post-treatment MCV, but also for the pre-treatment MCV. In fact, larger studies are required to assess whether delta MCV ≥ 10 fl is associated with PFS in MBC.…”

mentioning

confidence: 97%

Macrocytosis and dysplastic anemia is associated with the cyclin-dependent kinase 4/6 inhibitor palbociclib in metastatic breast cancer

et al. 2017

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dysplastic anemia is associated with the Cyclin-Dependent Kinase 4/6 inhibitor palbociclib in metastatic breast cancer. Haematologica. 2017; 102:xxx doi:10.3324/haematol.2017.181941 Publisher's Disclaimer. Hematopoiesis is a dynamic process that relies on active proliferation and differentiation of stem cells into erythrocytes, myelocytes, and platelets; processes that rely on coordinated progression through various phases of the cell-cycle. Neutropenia is a well-recognized adverse effect of palbociclib, and rapidly reversible when the drug is interrupted, but nevertheless occurs in 80% of patients treated with palbociclib, whereas anemia (24%) and thrombocytopenia (16%) are less Figure S2). No other common causes for macrocytosis were observed, including B12/folate deficiency, liver insufficiency, or hypothyroidism (Table S1). Unilateral bone marrow aspirate/biopsy in all 3 cases revealed moderately hypocellular marrow (~ 10% cellularity) with mildly decreased myeloid/erythroid ratio, dysplastic erythroid forms including binucleated forms, nuclear budding, small hypolobated megakaryocytes, and adequate stainable iron sores ( Figure 1F-M and Figure S2). Due to pathological similarities to MDS, cytogenetic/mutational analysis was conducted that did not reveal any pathogenic chromosomal alterations or mutations (GENOPTIX's 40-gene myeloid molecular profile). Flow cytometry did not reveal an increase in leukemic blasts. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.To determine the extent of macrocytosis in a larger cohort, we evaluated hematological parameters in 34 patients who had received palbociclib for ER+ MBC between January 1, 2015and March 1, 2017 (n=34). Hematological parameters during palbociclib treatment, maximum MCV and minimum Hb, were compared to baseline values using the Wilcoxon signed-rank test.Significant change in MCV (delta MCV) was defined as Figure S4); however, when delta MCV≥10 was included as time-dependent variable, this difference was not statistically significant (HR 0.59, p=0.4).These data suggest that palbociclib use led to a macrocytic, dysplastic anemia with bone marrow changes that mimic human MDS. Therefore, CDK4 and CDK6 expression by qRT-PCR was evaluated using MDS derived (n=183) and healthy (n=17) CD34+ hematopoietic stem cells (HSCs) obtained from a large cohort of gene expression profiles. CDK6 expression was significantly lower...

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“…There are 2 general etiologies of macrocytic anemias (MCV > 100 fL) 4 -red cell membrane defects and DNA synthesis defects. Red cell membrane defects can occur in the setting of liver disease or hypothyroidism.…”

Section: Classificationmentioning

confidence: 99%

“…Both serum and red cell folate concentration lack diagnostic specificity and, like vitamin B 12 deficiency, the use of metabolite assays are more accurate. 4 Lack of folate leads to elevation in serum homocysteine levels. Because vitamin B 12 deficiency can also lead to elevated homocysteine, methylmalonic acid levels should be incorporated into the workup for folate deficiency.…”

Section: Other Nutritional Deficienciesmentioning

confidence: 99%