http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(8): 883–888 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.938044
ORIGINAL ARTICLE
Red blood cell distribution width: reference intervals for neonates Robert D. Christensen1, Hassan M. Yaish2, Erick Henry1,3, and Sterling T. Bennett4 1
Department of Women and Newborns, Intermountain Healthcare, McKay-Dee Hospital Center, Ogden, UT, USA, 2Department of Pediatrics, Division of Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA, 3The Institute for Healthcare Delivery Research, and 4Department of Pathology, Intermountain Medical Center, Murray, Salt Lake City, UT, USA
Abstract
Keywords
Objective: To create reference intervals for red blood cell distribution width (RDW) of neonates and to use these intervals to better understand and classify hematopathology of neonates. Study design: This was a retrospective analysis of data from neonates born between 1/1/2001 and 12/31/2011, who had a complete blood cell count (CBC) in the first 14 days. The first RDW recorded from each was displayed according to gestational and postnatal age. Correlation between RDW and reticulocyte count was sought when the two tests were obtained simultaneously. Focused studies were performed on the 20 neonates with the highest and the 10 with the lowest RDW values. Results: RDW values from 165 613 CBCs were included. RDW reference intervals for neonates are higher than for older children and adults. At birth, the lower reference limit for term and late preterm neonates is 15.5%. The upper reference limit is 20%, and is slightly higher (up to 23%) in preterm neonates. For term and late preterm neonates the range does not change in the first two weeks but preterm neonates have a rise in upper reference limit concordant with erythrocyte transfusions. RDW and reticulocytes correlated positively but weakly (r2 ¼ 0.187). Eighteen of the 20 with the highest RDW values (29.4–42.8%) at birth had anemia with prenatal hemorrhage or hemolysis. Those with the lowest RDW values (11.8–13.7%) at birth tended to have a low MCV for age (95.5 ± 11.4 fL versus.129.8 ± 19.3 fL with a high RDW, p50.00001). Conclusion: The RDW reference interval at birth is 15.5–20% and does not change appreciably over the first two weeks except for those receiving a transfusion where the RDW increases. High RDW values at birth indicate anisocytosis commonly due to macrocytic reticulocytosis; low values correlate with relative microcytosis.
Anemia, erythrocyte, hematocrit, RBC indices, RDW, red cell distribution width
Introduction The red cell distribution width (RDW) describes the variation in red blood cell volume within a blood sample. Standard complete blood cell counts (CBC) include the RDW as a numerical expression of erythrocyte anisocytosis [1]. The RDW is calculated from the distribution of RBC volumes, measured by impedance, using the formula: RDW ¼ Standard deviation of RBC volume MCV ðmean corpuscular volumeÞ 100 The ‘‘width’’ in RDW refers to the width of the volumedistribution histogram, expressed as a coefficient of variation.
Address for correspondence: Robert D. Christensen, MD, Department of Women and Newborns, Intermountain Healthcare, NICU 4th Floor, McKay-Dee Hospital Center, 4401 Harrison Blvd, Ogden, UT 84403, USA. E-mail: [email protected]
History Received 24 March 2014 Revised 31 May 2014 Accepted 20 June 2014 Published online 17 July 2014
With mixtures of small and large red blood cells the histogram is wider, thus the RDW value is higher. Contrariwise with homogeneous red cell size the histogram is narrower, thus the RDW is lower. The reference interval for RDW among healthy adults ranges from 12 (lower reference interval limit) to 15% (upper reference interval limit) [2,3]. Alter et al. [4] and Tonbul et al. [5] reported RDW values for relatively small number of neonates, but reference intervals based on large number of neonates are not available.
Materials and methods We conducted a retrospective analysis of clinical and laboratory data existing in the Intermountain Healthcare data repositories. Altitudes of the hospitals contributing data ranged from 800 to 1520 m. The Intermountain Healthcare Institutional Review Board approved the study as a deidentified data-only investigation not requiring written consent of the individuals. Our approach for creating reference intervals was to first electronically obtain all CBCs on all neonates in our health system with a date of birth from 1 January 2001 to 31 December 2011. The CBCs were ordered by attending
884
R. D. Christensen et al.
J Matern Fetal Neonatal Med, 2015; 28(8): 883–888
physicians for clinical purposes and were not part of a protocol or study. All blood tests were performed in accordance with Intermountain Healthcare Laboratory Services standard operating procedures. Blood samples (0.25–0.40 mL) were drawn into EDTA-containing microtubes and assayed on Beckman Coulter hematology analyzers (Beckman Coulter Inc., Fullerton, CA). The reference intervals we used for MCV [6] and for hemoglobin and hematocrit during the neonatal period [7] are those we previously published from Intermountain Healthcare data bases. Gestational age was determined by obstetrical assignment unless this was changed by the neonatologist on the basis of gestational age assessment (based on physical examination and neurological–neurodevelopmental findings). The program used for clinical data collection was a modified subsystem of ‘‘clinical workstation’’. Clinical workstation is a web-based electronic medical record application that stores demographic and clinical information, such as history, physical examination results, laboratory data, problem lists and discharge summaries. 3M Company (St. Paul, MN) approved the structure and definitions of all data points for use within the program. Mean, 5th and 95th percentiles were used to express the reference intervals of all data obtained in the first 14 days following birth. When neonates had multiple CBCs only the first value from each patient was used. This is to avoid possible skewing due to multiple counts on infants with abnormal counts. RDW values from neonates with a hemoglobin or hematocrit outside our previously published reference intervals (5th to 95th percentile) were deleted from the data set, because those RDW values were possibly not representative of a true reference range [7]. The relationship between RDW and reticulocyte count was assessed by ANOVA. Focused chart reviews were conducted for the 20 neonates with the highest and the 10 with the lowest RDW values. Means and standard deviations were used to express values in groups that were normally distributed, and median and ranges in groups that were not. A Student t-test was used
to assess continuous variables. Statistical significance was set as p50.05.
Results Reference intervals for RDW, compiled from 57 658 neonates at birth, are shown in Figure 1, displayed according to gestational age. The lower reference interval was 15.5% across the gestational age range. The upper reference limit was 20% in term and late preterm infants and slightly higher at earlier gestational ages. Reference intervals for RDW over the first 24 h were stable. Figure 2 shows the mean RDW over the first two weeks (n ¼ 57 658 neonates at birth plus another 68 108 neonates through day 14), according to gestational age category. RDW values for term and late preterm neonates declined slightly over this period, while values from preterm infants increased. The earliest gestation group (29 weeks gestation at birth) had an increase in RDW 1–2 days after birth, and those born at 30–33weeks had a lesser increase about day 5. These increases were concordant with a receipt of allogenic RBC transfusions. As shown in Figure 3 (n ¼ 165 613 RDW values from 125 766 neonates), the group that received a RBC transfusion in the first two weeks, before their RDW was measured, had higher RDW values. This was so in all gestational age groups, although transfusions were rare in all except the most premature group. The effect of RBC transfusion on RDW was further examined in a sub-set analysis, comparing RDW before versus within 24 h following the first RBC transfusion, administered in the first three days of life. Each of 20 paired values had an increase in RDW following the transfusion (19.0 ± 2.4 before versus 28.3 ± 4.0 after, mean ± SD, p50.0001). A correlation between RDW and reticulocyte count is shown in Figure 4. Every CBC in the data set that had a simultaneous reticulocyte count (n ¼ 739) included in the analysis. The RDW and reticulocyte count correlated positively but weakly (R2 ¼ 0.187).
25
Figure 1. Red blood cell distribution width (RDW) on the day of birth as a function of gestational age. The lower dashed line shows the 5th percentile reference interval limit, the solid middle line shows the mean, and the upper dashed line shows the 95th percentile reference interval limit.
20
RDW (%)
15
10
5
0 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Weeks Gestaon
RDW – neonatal reference intervals
DOI: 10.3109/14767058.2014.938044
885
25
Figure 2. Mean values for RDW over the first two weeks as related to gestational age at birth.
20
RDW (%)
15
10
5
0 0D
1D
2D
3D
4D
5D
6D
7D
8D
9D
10D 11D 12D 13D 14D
Extremely Premature (
ORIGINAL ARTICLE
Red blood cell distribution width: reference intervals for neonates Robert D. Christensen1, Hassan M. Yaish2, Erick Henry1,3, and Sterling T. Bennett4 1
Department of Women and Newborns, Intermountain Healthcare, McKay-Dee Hospital Center, Ogden, UT, USA, 2Department of Pediatrics, Division of Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA, 3The Institute for Healthcare Delivery Research, and 4Department of Pathology, Intermountain Medical Center, Murray, Salt Lake City, UT, USA
Abstract
Keywords
Objective: To create reference intervals for red blood cell distribution width (RDW) of neonates and to use these intervals to better understand and classify hematopathology of neonates. Study design: This was a retrospective analysis of data from neonates born between 1/1/2001 and 12/31/2011, who had a complete blood cell count (CBC) in the first 14 days. The first RDW recorded from each was displayed according to gestational and postnatal age. Correlation between RDW and reticulocyte count was sought when the two tests were obtained simultaneously. Focused studies were performed on the 20 neonates with the highest and the 10 with the lowest RDW values. Results: RDW values from 165 613 CBCs were included. RDW reference intervals for neonates are higher than for older children and adults. At birth, the lower reference limit for term and late preterm neonates is 15.5%. The upper reference limit is 20%, and is slightly higher (up to 23%) in preterm neonates. For term and late preterm neonates the range does not change in the first two weeks but preterm neonates have a rise in upper reference limit concordant with erythrocyte transfusions. RDW and reticulocytes correlated positively but weakly (r2 ¼ 0.187). Eighteen of the 20 with the highest RDW values (29.4–42.8%) at birth had anemia with prenatal hemorrhage or hemolysis. Those with the lowest RDW values (11.8–13.7%) at birth tended to have a low MCV for age (95.5 ± 11.4 fL versus.129.8 ± 19.3 fL with a high RDW, p50.00001). Conclusion: The RDW reference interval at birth is 15.5–20% and does not change appreciably over the first two weeks except for those receiving a transfusion where the RDW increases. High RDW values at birth indicate anisocytosis commonly due to macrocytic reticulocytosis; low values correlate with relative microcytosis.
Anemia, erythrocyte, hematocrit, RBC indices, RDW, red cell distribution width
Introduction The red cell distribution width (RDW) describes the variation in red blood cell volume within a blood sample. Standard complete blood cell counts (CBC) include the RDW as a numerical expression of erythrocyte anisocytosis [1]. The RDW is calculated from the distribution of RBC volumes, measured by impedance, using the formula: RDW ¼ Standard deviation of RBC volume MCV ðmean corpuscular volumeÞ 100 The ‘‘width’’ in RDW refers to the width of the volumedistribution histogram, expressed as a coefficient of variation.
Address for correspondence: Robert D. Christensen, MD, Department of Women and Newborns, Intermountain Healthcare, NICU 4th Floor, McKay-Dee Hospital Center, 4401 Harrison Blvd, Ogden, UT 84403, USA. E-mail: [email protected]
History Received 24 March 2014 Revised 31 May 2014 Accepted 20 June 2014 Published online 17 July 2014
With mixtures of small and large red blood cells the histogram is wider, thus the RDW value is higher. Contrariwise with homogeneous red cell size the histogram is narrower, thus the RDW is lower. The reference interval for RDW among healthy adults ranges from 12 (lower reference interval limit) to 15% (upper reference interval limit) [2,3]. Alter et al. [4] and Tonbul et al. [5] reported RDW values for relatively small number of neonates, but reference intervals based on large number of neonates are not available.
Materials and methods We conducted a retrospective analysis of clinical and laboratory data existing in the Intermountain Healthcare data repositories. Altitudes of the hospitals contributing data ranged from 800 to 1520 m. The Intermountain Healthcare Institutional Review Board approved the study as a deidentified data-only investigation not requiring written consent of the individuals. Our approach for creating reference intervals was to first electronically obtain all CBCs on all neonates in our health system with a date of birth from 1 January 2001 to 31 December 2011. The CBCs were ordered by attending
884
R. D. Christensen et al.
J Matern Fetal Neonatal Med, 2015; 28(8): 883–888
physicians for clinical purposes and were not part of a protocol or study. All blood tests were performed in accordance with Intermountain Healthcare Laboratory Services standard operating procedures. Blood samples (0.25–0.40 mL) were drawn into EDTA-containing microtubes and assayed on Beckman Coulter hematology analyzers (Beckman Coulter Inc., Fullerton, CA). The reference intervals we used for MCV [6] and for hemoglobin and hematocrit during the neonatal period [7] are those we previously published from Intermountain Healthcare data bases. Gestational age was determined by obstetrical assignment unless this was changed by the neonatologist on the basis of gestational age assessment (based on physical examination and neurological–neurodevelopmental findings). The program used for clinical data collection was a modified subsystem of ‘‘clinical workstation’’. Clinical workstation is a web-based electronic medical record application that stores demographic and clinical information, such as history, physical examination results, laboratory data, problem lists and discharge summaries. 3M Company (St. Paul, MN) approved the structure and definitions of all data points for use within the program. Mean, 5th and 95th percentiles were used to express the reference intervals of all data obtained in the first 14 days following birth. When neonates had multiple CBCs only the first value from each patient was used. This is to avoid possible skewing due to multiple counts on infants with abnormal counts. RDW values from neonates with a hemoglobin or hematocrit outside our previously published reference intervals (5th to 95th percentile) were deleted from the data set, because those RDW values were possibly not representative of a true reference range [7]. The relationship between RDW and reticulocyte count was assessed by ANOVA. Focused chart reviews were conducted for the 20 neonates with the highest and the 10 with the lowest RDW values. Means and standard deviations were used to express values in groups that were normally distributed, and median and ranges in groups that were not. A Student t-test was used
to assess continuous variables. Statistical significance was set as p50.05.
Results Reference intervals for RDW, compiled from 57 658 neonates at birth, are shown in Figure 1, displayed according to gestational age. The lower reference interval was 15.5% across the gestational age range. The upper reference limit was 20% in term and late preterm infants and slightly higher at earlier gestational ages. Reference intervals for RDW over the first 24 h were stable. Figure 2 shows the mean RDW over the first two weeks (n ¼ 57 658 neonates at birth plus another 68 108 neonates through day 14), according to gestational age category. RDW values for term and late preterm neonates declined slightly over this period, while values from preterm infants increased. The earliest gestation group (29 weeks gestation at birth) had an increase in RDW 1–2 days after birth, and those born at 30–33weeks had a lesser increase about day 5. These increases were concordant with a receipt of allogenic RBC transfusions. As shown in Figure 3 (n ¼ 165 613 RDW values from 125 766 neonates), the group that received a RBC transfusion in the first two weeks, before their RDW was measured, had higher RDW values. This was so in all gestational age groups, although transfusions were rare in all except the most premature group. The effect of RBC transfusion on RDW was further examined in a sub-set analysis, comparing RDW before versus within 24 h following the first RBC transfusion, administered in the first three days of life. Each of 20 paired values had an increase in RDW following the transfusion (19.0 ± 2.4 before versus 28.3 ± 4.0 after, mean ± SD, p50.0001). A correlation between RDW and reticulocyte count is shown in Figure 4. Every CBC in the data set that had a simultaneous reticulocyte count (n ¼ 739) included in the analysis. The RDW and reticulocyte count correlated positively but weakly (R2 ¼ 0.187).
25
Figure 1. Red blood cell distribution width (RDW) on the day of birth as a function of gestational age. The lower dashed line shows the 5th percentile reference interval limit, the solid middle line shows the mean, and the upper dashed line shows the 95th percentile reference interval limit.
20
RDW (%)
15
10
5
0 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Weeks Gestaon
RDW – neonatal reference intervals
DOI: 10.3109/14767058.2014.938044
885
25
Figure 2. Mean values for RDW over the first two weeks as related to gestational age at birth.
20
RDW (%)
15
10
5
0 0D
1D
2D
3D
4D
5D
6D
7D
8D
9D
10D 11D 12D 13D 14D
Extremely Premature (
