Anaemia is a common complication in cancer patients. The decrease in haemoglobin is associated with an impaired quality of life, poorer response to therapy and worse prognosis. Numerous factors are involved in the physiopathology of cancer-related anaemia. Some factors such as bleeding, bone marrow infiltration, the effects of chemoradiotherapy and associated nutritional deficiencies are related to the disease itself. In addition, the interaction of the immune system with iron metabolism and erythropoiesis has been shown to be an important factor in the development of anaemia in cancer patients and can be seen in the action of several cytokines on different iron-homeostasis and erythrocyte-cell-production pathways. Some inhibitory cytokines, such as tumour necrosis factor-alpha and interleukin-1, act on the suppression of erythroid precursor cells and erythropoietic production and response; others, such as interleukins 1 and 6 and hepcidin, impair iron metabolism, causing iron to be diverted from erythropoiesis and retained within the reticuloendothelial system. The main mechanisms involved in the development of cancer-related anaemia are discussed in this review.

Iron metabolism: an overview on the main mechanisms involved in its homeostasisHelena Z. W. Grotto Um perfeito sincronismo entre absorção, utilização e estoque de ferro é essencial para a manutenção do equilíbrio desse metal no organismo. Alterações nesses processos podem levar tanto à deficiência como ao seu acúmulo de ferro, duas situações com repercussões clínicas e laboratoriais importantes para o paciente. Essa revisão aborda os diversos aspectos relacionados com a cinética do ferro, descrevendo as proteínas e mediadores nela envolvidos. Apresenta, ainda, como é feita a regulação intracelular e sistêmica do ferro que visa a manutenção de uma quantidade ótima de ferro para o metabolismo das células e, em especial, para uma perfeita hematopoiese. É discutido também o importante papel da hepcidina, como regulador da homeostase sistêmica. Será a apresenta da a relação entre a hepcidina e a resposta de fase aguda, e como as alterações na expressão da hepcidina podem contribuir com a fisiopatogênese da anemia de doença crônica.

ObjectiveThe aim of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters to identify three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency.MethodsPeripheral blood cells from 117 adult patients with anemia were classified according to iron status, inflammation, and hemoglobinopathies as: iron deficiency anemia (n = 42), anemia of chronic disease (n = 28), anemia of chronic disease associated with iron deficiency anemia (n = 22), and heterozygous β-thalassemia (n = 25). The percentage of microcytic erythrocytes, hypochromic erythrocytes, and the levels of hemoglobin in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating anemia.ResultsThere was no difference between the groups of iron deficiency and anemia of chronic disease associated with absolute iron deficiency for any of the parameters. The percentage of hypochromic erythrocytes was the best parameter to identify absolute iron deficiency in patients with anemia of chronic disease (area under curve = 0.785; 95% confidence interval: 0.661–0.909 with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic erythrocyte count minus hypochromic erythrocyte count was very accurate to differentiate iron deficiency anemia from heterozygous β-thalassemia (area under curve = 0.977; 95% confidence interval: 0.950–1.005 with a sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8).ConclusionThe erythrocyte and reticulocyte indices are moderately good to identify absolute iron deficiency in patients with anemia of chronic disease.

The purpose of this study was to evaluate reticulocyte parameters by means of flow cytometric reticulocyte counting in a group of patients who had undergone autologous and allogeneic bone marrow transplantation (BMT). The pattern of reticulocyte response and the predictive value of absolute neutrophil count (ANC), platelet count, number of CD34+ cell infused and graft source for reticulocyte response were studied. We compared absolute reticulocyte count (RetAbs), mean fluorescence index (MFI) and mean reticulocyte volume/mean corpuscular volume (MRV/MCV) ratio with conventional criteria (ANC and platelet count) in 22 allogeneic and 20 autologous BMT recipients. An abrupt increase in MRV/MCV ratio or a rise in MFI value were the earliest signs of erythropoietic recovery following allogeneic transplantation (63.6 and 22.8% of cases, respectively). In 13.6% of the cases, both parameters were observed simultaneously. All but three autologous transplant recipients showed changes in reticulocyte parameters earlier than ANC recovery. Granulocyte recovery and peripheral blood progenitor cells (PBPC) graft were predictive variables for RetAbs response in allogeneic transplant recipients. In the autologous group, predictive variables for RetAbs response were a high number of CD34+ infused cells and platelet recovery. An increase in the immature reticulocyte population is the earliest sign of haematopoietic recovery following BMT.

New parameters correlated with the hemoglobin content in reticulocytes (RET-Y) and in red blood cells (RBC-Y) have been suggested as helpful in diagnosing iron deficiency anemia. We have studied RET-Y and RBC-Y indices in two groups of patients with microcytosis to verify if these parameters could be used to differentiate iron deficiency anemia from beta-thalassemia minor. Blood samples from 33 iron-deficient patients, 25 beta-thalassemic minor patients and 50 normal individuals were analyzed on a Sysmex XE-2100 instrument. A significant difference was observed in reticulocyte counting and immature reticulocyte fraction between iron deficiency anemia and beta-thalassemia minor groups, but not in RBC-X and RET-Y parameters. Reticulocyte counting was higher in beta-thalassemia minor and the immature reticulocyte fraction was higher in severe iron deficiency anemia. The ratio RET-Y/mean cell volume was tested and was significantly different when beta-thalassemia minor was compared with mild and severe iron deficiency anemia, and showed better performance than the Mentzer ratio and the Green and King function. A great overlap of RET-Y and RBC-Y individual values was observed in both groups of microcytic anemias; we conclude that these new indices may be used with caution as indicative of iron deficiency, mainly in populations where beta-thalassemia minor is frequent.