Effect of Hydroxyurea on Immature Reticulocyte Fraction in Sickle Cell Anemia

Abstract

Immature reticulocyte fraction (IRF) is a good indicator of bone marrow erythropoiesis in response to hemolysis or tissue hypoxia and is markedly increased in sickle cell disease (SS). We compared IRF changes in SS patients with those who were treated with hydroxyurea (SS-HU), and those who had concurrent alpha globin gene deletion (SS-(- deletion). Forty-two patients including 16 SS, 16 SS-HU, and 10 SS-alpha-deletion patients were studied. Significant decreases (P <.01) in reticulocyte indices including IRF, the reticulocyte percentage, and absolute reticulocyte count (ARC) were observed in SS-alpha-deletion compared to SS patients. On the other hand, although the reticulocyte percentage (P <.01) and ARC (P <.01) were significantly decreased in SS-HU compared with SS patients, the IRF was persistently elevated in both groups (P = .4), suggesting continuous bone marrow stimulation in SS-HU patients in response to tissue hypoxia. The possible underlying physiological mechanisms are discussed.

Reticulocyte Antioxidant Enzymes mRNA Levels versus Reticulocyte Maturity Indices in Hereditary Spherocytosis, β-Thalassemia and Sickle Cell Disease

“…Their RPI values were significantly lower than in HS, showing that in SCD, the erythropoietic response is less efficient or impaired. In fact, we observed the most immature reticulocyte profile in SCD, with the highest IRF and the lowest LFRs (Table 1), as reported by others [14,15,[38][39][40]. This was also supported by the extremely high levels of all mRNA transcripts, especially when comparing their average increase to the controls (Figure 1F).…”

Guideline for the laboratory diagnosis of functional iron deficiency

“…Immature reticulocytes are released during periods of intense erythropoietic stimulation, such as following haemorrhage or haemolysis, or in response to therapy with iron or ESAs. The IRF increases several days before the reticulocyte count (Davies, 1996) and is thus an early indicator of response to therapy. Nevertheless, the test is little used, probably because of a lack of standardization of methods and instrument-or method-specific reference ranges.…”

Biological Variations of Hematologic Parameters Determined by UniCel DxH 800 Hematology Analyzer

“…Importantly, some of these new parameters have demonstrated useful clinical applications. [10][11][12][13][14][15][16][17][18] For example, immature reticulocyte fraction, which is defined as the ratio of immature to total reticulocytes, has been proposed as a new hematologic parameter in the evaluation of erythropoietic activity. 10 Its main clinical value is that the immature reticulocyte fraction has been shown to be an earlier and more sensitive indicator of bone marrow stimulation than other traditionally used reticulocyte parameters, such as the absolute reticulocyte count and the reticulocyte percentage.…”

“…[10][11][12][13] This feature is particularly important in certain clinical circumstances, such as evaluation of bone marrow recovery after chemotherapy or stem cell transplantation; the response to therapy with iron, folate, and vitamin B 12 in anemic patients; and neonatal monitoring. [10][11][12][13] Low hemoglobin density is another new parameter available from the DxH800; it is derived from the mean corpuscular hemoglobin concentration (MCHC) using the mathematical sigmoid transformation [LHD ¼ 100 3 ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ffi ð1 À ð1=1 þ eð1:8ð30 À MCHCÞÞÞÞ p ]. Low hemoglobin density has been shown to be a reliable parameter for the detection of patients with iron-deficiency anemia even in the presence of inflammation.…”