Performing your original search, RETICULOCYTE HEMOGLOBIN CONTENT, in PubMed will retrieve 328 records.

Am J Hematol. 2008 Apr;83(4):307-10.

Reticulocyte hemoglobin content.

Mast AE, Blinder MA, Dietzen DJ. Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53201-2178, USA. alan.mast@bcw.edu Under normal conditions, reticulocytes are the youngest erythrocytes released from the bone marrow into circulating blood. They mature for 1-3 days within the bone marrow and circulate for 1-2 days before becoming mature erythrocytes. Measurement of cellular hemoglobin concentration has long been reported by automated hematology analyzers as one of the red blood cell indices. The reticulocyte hemoglobin content (CHr or Ret-He) provides an indirect measure of the functional iron available for new red blood cell production over the previous 3-4 days. Measurement of reticulocyte hemoglobin content in peripheral blood samples is useful for diagnosis of iron deficiency in adults (Mast et al., Blood 2002;99:1489-1491) and children (Brugnara et al., JAMA 1999;281:2225-2230; Ullrich et al., JAMA 2005;294:924-930; Bakr and Sarette, Eur J Pediatr 2006;165:442-445). It provides an early measure of the response to iron therapy increasing within 2-4 days of the initiation of intravenous iron therapy (Brugnara et al., Blood 1994;83:3100-3101). Sequential measurements of reticulocyte hemoglobin content in patients with iron deficiency anemia provide a rapid means for assessing the erythropoietic response to iron replacement therapy (Brugnara et al., Blood 1994;83:3100-3101). It is also an early indicator or iron-restricted erythropoiesis in patients receiving erythropoietin therapy (Fishbane et al., Kidney Int 1997;52:217-222; Fishbane et al., Kidney Int 2001;60:2406-2411; Mittman et al., Am J Kidney Dis 1997;30:912-922; Tsuchiya et al., Clin Nephrol 2003;59:115123; Chuang et al., Nephrol Dial Transplant 2003;18:370-377). Thus, reticulocyte hemoglobin content is a recent addition to an expanding list of biomarkers that can be used to differentiate iron deficiency from other causes of anemia. (c) 2007 Wiley-Liss, Inc.

Original Paper Clinical Interpretation of Reticulocyte Hemoglobin Content, RET-Y, in Chronic Hemodialysis Patients Hwee-Yeong Nga, c, Hung-Chun Chenc, Lin-Lin Panb, Yu-Che Tsaia, Kao-Tai Hsua, Shang-Chih Liaoa, Fong-Rong Chuanga, Jin-Bor Chena, Chien-Te Leea
a b

Division of Nephrology, Department of Internal Medicine, and Department of Clinical Pathology, Chang Gung Memorial Hospital, Kaohsiung Medical Center,

Chang Gung University College of Medicine, and c Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Address of Corresponding Author Nephron Clin Pract 2009;111:c247-c252 (DOI: 10.1159/000209151)

Key Words

Anemia Hemodialysis RET-Y Ferritin Transferrin saturation

Abstract Background: Iron deficiency is the most common factor associated with erythropoietin (EPO) hyporesponsiveness. Current iron indices are inadequate to demonstrate the status or utility of iron in erythropoiesis. The aims of this study are to investigate the value of the reticulocyte hemoglobin content, RET-Y, in hemodialysis (HD) patients and compare the levels with conventional iron indices. Methods: HD patients (n = 289) were divided into 4 groups according to serum ferritin (cutoff value 100 ng/ml) and transferrin saturation (TSAT, cutoff value 20%). The RET-Y value, hemogram and biochemical data were determined and compared between groups. Factors associated with RET-Y were examined. Results: The mean RET-Y value was 1,716 125 AU. Patients with absolute iron deficiency had lower RET-Y levels and mean corpuscular volume (MCV). Patients with functional iron deficiency had a lower reticulocyte production index and serum albumin levels. MCV, mean corpuscular hemoglobin concentration (MCHC) and albumin were independently correlated with the RET-Y level (all p < 0.001). EPOindependent patients had low iron indices and low RET-Y levels, but a higher reticulocyte production index and albumin levels were noted. Conclusion: RET-Y levels in HD patients were close to that of the normal population. Low RET-Y levels were observed in patients with absolute iron deficiency and also in EPO-independent patients with low ferritin and low TSAT. There was a strong association between the serum albumin and RET-Y levels in chronic HD patients. Copyright 2009 S. Karger AG, Basel Reticulocyte Hemoglobin Detects Iron Deficit in Infants

Clinical Question: Is reticulocyte hemoglobin content the preferred screening tool for the early detection of iron deficiency in infants? Setting: Outpatient (any) Study Design: Cohort (prospective) Synopsis: Iron deficiency in infants is linked with impaired mental and motor development that may be long lasting. Relying on the measurement of hemoglobin misses children with early iron deficiency who are not yet anemic. The authors of this study prospectively monitored 202 healthy infants nine to 12 months of age to compare reticulocyte hemoglobin content with hemoglobin in screening for iron deficiency. Hemoglobin is derived from the entire population of red blood cells, each with a lifespan of approximately 120 days, but the reticulocytedependent hemoglobin measurement relies on only the 24- to 48-hour lifespan of the reticulocyte. Monitoring of 84 percent of the infants occurred for a median duration of 5.6 months. The authors did not specify whether the results were interpreted blindly, but the same automated hematology analyzer performed all tests, so it is likely they were. A total of 23 infants (11.4 percent) had iron deficiency (serum transferrin saturation less than 10 percent), and six (3 percent) had iron deficiency and anemia (hemoglobin less than 11 g per dL [110 g per L]). The optimal cutoff level for detecting iron deficiency with reticulocyte hemoglobin content was 27.5 pg (sensitivity = 83 percent; specificity = 72 percent). Screening with a threshold hemoglobin level of less than 11 g per dL resulted in a sensitivity of 26 percent and a specificity of 95 percent. Bottom Line: A low reticulocyte hemogobin content has a higher sensitivity for the accurate detection of early iron deficiency in infants than a standard hemoglobin measurement. Randomized trials comparing infants undergoing screening with either technique or no screening at all are now necessary to assess the long-term value of screening. (Level of Evidence: 2b)

Reticulocyte hemoglobin measurement comparison of two methods in the diagnosis of iron-restricted erythropoiesis
Lothar Thomas,

1. Department of Laboratory Medicine, Krankenhaus Nordwest, Frankfurt am Main, Germany

1

Susanne Franck,

2. Department of Laboratory Medicine, Krankenhaus Nordwest, Frankfurt am Main, Germany

2

Maren Messinger,

3. Department of Laboratory Medicine, Krankenhaus Nordwest, Frankfurt am Main, Germany

Jo Linssen,

4. Sysmex Scientific Department, Norderstedt, Germany

4

Marcus Thom,

5. Department of Laboratory Medicine, Krankenhaus Nordwest, Frankfurt am Main, Germany

5

Christian Thomas

6. Department of Urology and Pediatric Urology, Johannes Gutenberg University, Mainz, Germany
6

Corresponding author: Lothar Thomas, MD, Department of Laboratory Medicine, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488 Frankfurt, Germany Phone: +49-69-76013252, Fax: +49-69-78 73 40, Citation Information. Clinical Chemical Laboratory Medicine. Volume 43, Issue 11, Pages 11931202, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2005.207, 01/11/2005 Publication History: Received: //; accepted: //; published online: 19/10/2005

Abstract

The aims of this study were to diagnose iron-restricted erythropoiesis (functional iron deficiency) in patients with classic iron deficiency (ID), anemia of chronic disease (ACD) and the combined state of ID/ACD with the use of two hematological methods for the measurement of reticulocyte hemoglobinization. In comparison, the biochemical markers of iron status were determined. We studied 474 anemic patients admitted to hospital with a broad spectrum of diseases. We measured indicators of reticulocyte hemoglobinization. CHr was determined on an Advia 120 hematology analyzer. A Sysmex XE-2100 hematology analyzer was used to determine RET-Y, the forward scatter of fluorescence-labeled reticulocytes, which can also be expressed as the reticulocyte hemoglobin equivalent (RET-He), as well as RBC-Y, the forward scatter of fluorescence-labeled erythrocytes, which can be expressed as the erythrocyte hemoglobin equivalent. Ferritin, soluble transferrin receptor (sTfR) and the sTfR/log ferritin ratio (sTfR-F index) were used as biochemical markers. The comparison of RET-Y with CHr demonstrated an excellent curvilinear relationship between the two parameters. The normal reference range for

Ret-Y was 16301860 arbitrary units (AU); mathematical transformation to RET-He gave a range of 28.235.7 pg. Correlations of biochemical iron markers with RET-He were as weak as with CHr in patients with ACD and acute phase response. In a diagnostic plot to identify iron status, RET-He could replace CHr without any loss of sensitivity or specificity. Patient mismatch analysis between RET-He and CHr in the diagnostic plot demonstrated agreement for 449 of 474 patients (94.4%). Patient specific anemia mismatches were 2.96.2%. According to our results, the indicators of reticulocyte hemoglobinization, RET-He and CHr, measure the same phenomenon. RET-He is as valuable as CHr for the diagnosis of iron-restricted erythropoiesis. The combination of RET-He and the sTfR-F index in a diagnostic plot offers an attractive tool for the evaluation of iron status and identification of the progression of ID. Keywords acute-phase response, anemia of chronic disease, functional iron deficiency, ironrestricted erythropoiesis, reticulocyte hemoglobin

Low hemoglobin concentration cell percentage and method of use in detection of iron deficiency description/claims
The Patent Description & Claims data below is from USPTO Patent Application 20070172955, Low hemoglobin concentration cell percentage and method of use in detection of iron deficiency. Brief Patent Description - Full Patent Description - Patent Application Claims

CROSS REFERENCE TO RELATED APPLICATION [0001]This application claims the benefit under 35 USC 119 (e) of the provisional patent application Ser. No. 60/760,520, filed on Jan. 20, 2006, which is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION [0002]The present invention relates to a method of producing a new diagnostic parameter, low hemoglobin concentration cell percentage, and the method of use in detection of iron deficiency. BACKGROUND OF THE INVENTION [0003]Iron deficiency (ID) is the most prevalent single deficiency state on a worldwide basis. It is important economically because it diminishes the capability of individuals who are affected to perform physical labor, and it diminishes both growth and learning in children.

[0004]Absolute iron deficiency, with anemia or without anemia, and functional iron deficiency (FID) are high frequency clinical conditions, and these patients have iron deficient erythropoiesis. Absolute iron deficiency is defined as a decreased total iron body content. Iron deficiency anemia (IDA) occurs when iron deficiency is sufficiently severe to diminish erythropoiesis and cause the development of anemia. Functional iron deficiency describes a state where the total iron content of the body is normal or even elevated, but the iron is `locked away` and unavailable for the production of red blood cells. This condition is observed mainly in patients with chronic renal failure who are on hemodialysis, and in patients with chronic inflammation or chronic infections. [0005]Iron status can be measured using hematological and biochemical indices. Each parameter of iron status reflects changes in different body iron compartments and is affected at different levels of iron depletion. Specific iron measurements include hemoglobin (Hgb), mean cell volume (MCV), hematocrit (Hct), erythrocyte protoporphyrin, plasma iron, transferrin, transferrin saturation levels (TSAT), serum ferritin (SF) and more recently soluble transferrin receptors (sTfR) and red-cell distribution width (RDW). [0006]Typical values for normal iron status are SF 100.+-.60 ng/mL and Hgb 12-17 g/dL for women and 14-19 g/dL for men. The typical values for iron deficiency anemia are SF<22 ng/mL, Hgb for women<12 g/dL and for men<13 g/dL. [0007]Hemoglobin (Hgb) has been used longer than any other iron status parameter. It provides a quantitative measure of the severity of iron deficiency once anemia has developed. Hemoglobin determination is a convenient and simple screening method and is especially useful when the prevalence of iron deficiency is high, as in pregnancy or infancy. The limitations of using hemoglobin as a measure of iron status are its lack of specificity (as factors such as vitamin B.sub.12 or folate deficiency, genetic disorders and chronic infections can limit erythropoiesis) and its relative insensitivity due to the marked overlap in values between normal and iron deficient populations. To identify iron deficiency anemia, hemoglobin is measured together with more selective measurements of iron status. [0008]A reduction in mean cell volume (MCV) occurs when iron deficiency becomes severe, at about the same time as anemia starts to develop. It is a fairly specific indicator of iron deficiency once thalassemia and the anemia of chronic disease have been excluded. A cut-off value of 80 fl is accepted as the lower limit of normal in adults. It has been reported that when measured on Technicon hematology analyzers (that use optical measurement of red blood cells) iron deficiency blood samples have reduced mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). However, when measured by impedance-based hematology analyzers (Such as Coulter or Sysmex instruments) MCHC is insensitive but more specific for iron deficiency (Bain, B. J., Blood Cells, A Practical Guide, Second Edition,

Blackwell Science Ltd., 1995, Chapter 8, pages 197-199). The red-cell distribution width (RDW) has been used recently in combination with other parameters for the classification of anemias. It reflects the variation in the size of the red cells and can be used to detect subtle degrees of anisocytosis. [0009]The most commonly used iron status parameters at present are transferrin saturation (TSAT) and serum ferritin (SF). However, both are indirect measures of iron status. Transferrin is a transport protein that contains two iron binding sites by which it transports iron from storage sites to erythroid precursors. TSAT (i.e., the percentage of total binding sites that are occupied by iron) is a measure of iron that is available for erythropoiesis. TSAT is calculated by dividing the serum iron by the total iron binding capacity (TIBC), a measurement of circulating transferrin, and multiplying by 100. Ferritin is a storage protein that is contained primarily within the reticuloendothelial system, with some amounts released in the serum. Under conditions of iron excess, ferritin production increases to offset the increase in plasma iron. The level of ferritin in the serum, therefore, reflects the amount of iron in storage. TABLE-US-00001 Definition of Functional Iron Deficiency (FID) and Absolute Iron Deficiency (AID) by Kidney Disease Outcomes, Quality Initiative K/DOQI (U.S.A) Ferritin .mu.g/L <100 100 800 TSAT <20% AID TSAT <20% FID [0010]For patients with chronic kidney disease, absolute iron deficiency may be diagnosed when TSAT is <20% and SF is <100 ng/ml. Functional iron deficiency may be more difficult to diagnose since iron status parameters may indicate adequate iron stores. There are different criteria in defining FID, one of them is published by the Kidney Disease Outcomes Quality Initiative--K/DOQI (Eknoyan G, et al. Continuous quality improvement: DOQI becomes K/DOQI and is updated. National Kidney Foundation's Dialysis Outcomes Quality Initiative. Am J Kidney Dis., 2001 January;37(1):179-194; Anemia Management in Chronic Kidney Disease: Role of Factors Affecting Epoetin Responsiveness, ESCHBACH, J., J Am Soc Nephrol 13: 1412-1414, 2002.), as shown in the table above. [0011]The limitations of using transferrin saturation reflect those of serum iron, i.e., wide diurnal variation and low specificity. TSAT is also reduced in inflammatory disease. Transferrin saturation is commonly used in population studies combined with other indicators of iron status. On the other hand, as ferritin is an acute phase reactant, its serum levels may be elevated in the presence of chronic inflammation, infection, malignancy and liver disease. Alcohol consumption has also been suggested to independently raise serum ferritin. [0012]Recently, several new red blood cell and reticulocyte parameters have been reported having utilities in detection of iron deficiency and functional iron deficiency. Two of the parameters are hypochromic red cell percentage (referred to

as % Hypo) and CHr (reticulocyte hemoglobin content) reported by the Bayer ADVIA 120 hematology analyzer (Thomas et al., Biochemical Markers and Hematologic Indices in the Diagnosis of Functional Iron Deficiency, Clinical Chemistry 48:7, 10661076, 2002). Hypochromic red cell percentage is defined as the percentage of red blood cells having hemoglobin concentration less than 28 g/dL. [0013]Reticulocytes are immature red blood cells with a life span of only 1 to 2 days. When these are first released from the bone marrow, measurement of their hemoglobin content can provide the amount of iron immediately available for erythropoiesis. A less than normal hemoglobin content in these reticulocytes is an indication of inadequate iron supply relative to demand. The amount of hemoglobin in these reticulocytes also corresponds to the amount of hemoglobin in mature red blood cells. CHr has been evaluated recently in numerous studies as a test for iron deficiency and functional iron deficiency and has been found to be highly sensitive and specific. However, exact threshold values have not been established, as the threshold values vary depending on the laboratory and instrument used. [0014]Erythropoietin is effective in stimulating production of red blood cells, but without an adequate iron supply to bind to hemoglobin, the red blood cells will be hypochromic, i.e., low in hemoglobin content. Thus, in states of iron deficiency, a significant percentage of red blood cells leaving the bone marrow will have a low hemoglobin content. By measuring the percentage of red blood cells with hemoglobin content <28 g/dL, iron deficiency can be detected. % Hypo>10% has been correlated with iron deficiency, and hence has been used as a diagnostic criterion for detection of iron deficiency (Revised European Best Practice Guidelines for the Management of Anaemia in Patients With Chronic Renal Failure, Locatelli, F. et al., Nephrology and Dyalisis Transplantation, Volume 19 May 2004 (Supplement 2), Guideline III.2, page ii22-24). [0015]% Hypo is a reported parameter on several Bayer hematology analyzers based on an optical cell-by-cell hemoglobin measurement. % Hypo must be measured using a fresh whole blood sample (less than four hours after blood collection), since storage or sample aging leads to erroneous increases of % Hypo report due to red blood cell swelling (Revised European Best Practice Guidelines for the Management of Anaemia in Patients With Chronic Renal Failure, Locatelli, F. et al., Nephrology and Dyalisis Transplantation, Volume 19 May 2004 (Supplement 2), Appendix B, page ii39-41). [0016]Two other parameters have been reported recently correlating to % Hypo and CHr are RBC--Y and Ret-H.sub.e reported by the Sysmex XE-2100 hematology analyzer (Machin S. J. et al. Functional Iron Deficiency and New Red Cell Parameters on the Sysmex XE-2100, ISLH 2001 Industry-Sponsored Workshops, ISLH XIVth International Symposium, 2001; and Thomas, C. et al., Anemia of Chronic Disease: Pathophysiology and Laboratory Diagnosis, Laboratory Hematology 2005, 11:14-

23). RBC--Y is the mean value of the forward light scatter histogram within the mature erythrocyte population, and Ret-H.sub.e is the mean value of the forward light scatter histogram within the reticulocyte population obtained in a reticulocyte measurement on the Sysmex XE-2100 hematology analyzer. [0017]Most recently, several functions of red blood cell parameters as well as reticulocyte parameters have been disclosed by Simon-Lopez in the co-pending application Ser. No. 11/524,682 to be useful in detection of iron deficiency. These include a RBC size function (RSf) defined as a product function of MCV and MRV, a volume-hemoglobin factor (VHf) defined as a product function of MCV and Hgb, a volume-hemoglobin/distribution factor (VHDWf) defined as a function of MCV, Hgb and RDW. [0018]It has been recognized that CHr and % Hypo are only provided on Bayer's hematology analyzers. Therefore, this information is not available for many clinical laboratories and hospitals. A need exists for developing new diagnostic indicators for detection iron deficiency with comparable clinical accuracy, sensitivity and specificity to the known parameters such as CHr and % Hypo. SUMMARY OF THE INVENTION [0019]In one embodiment, the present invention is directed to a method of producing low hemoglobin concentration cell percentage (LHCC %) on a hematology analyzer. The method comprises mixing a first aliquot of a blood sample with a blood diluent to form a first sample mixture, analyzing the first sample mixture on the hematology analyzer, and obtaining a mean cell volume of red blood cells (MCV) and a red blood cell concentration (RBC); mixing a second aliquot of the blood sample with a reagent system to form a second sample mixture, analyzing the second sample mixture on the hematology analyzer, and obtaining a hemoglobin concentration (Hgb) of the blood sample; obtaining mean cell hemoglobin concentration (MCHC) using the obtained MCV, RBC and Hgb; obtaining a low hemoglobin concentration cell percentage (LHCC %) using the obtained MCHC; and reporting the LHCC % of the blood sample on the hematology analyzer.