Appendices Reference Values in Infancy and Childhood





Carlo Brugnara



APPENDIX 1

Hematologic Values * in Normal Fetuses at Different Gestational Ages

















































Week of Gestation Hemoglobin (g/dL) RBCs (×10 6 /mL) Hematocrit (%) Mean Corpuscular Volume (fL) Total WBCs (×10 6 /µL Corrected WBCs (×10 6 /µL) Platelets (×10 6 /µL)
18-21 (N = 760) 11.69 ± 1.27 2.85 ± 0.36 37.3 ± 4.32 131.1 ± 11.0 4.68 ± 2.96 2.57 ± 0.42 234 ± 57
22-25 (N = 1200) 12.2 ± 1.6 3.09 ± 0.34 38.59 ± 3.94 125.1 ± 7.8 4.72 ± 2.82 3.73 ± 2.17 247 ± 59
26-29 (N = 460) 12.91 ± 1.38 3.46 ± 0.41 40.88 ± 4.4 118.5 ± 8.0 5.16 ± 2.53 4.08 ± 0.84 242 ± 69
>30 (N = 440) 13.64 ± 2.21 3.82 ± 0.64 43.55 ± 7.2 114.4 ± 9.3 7.71 ± 4.99 6.4 ± 2.99 232 ± 87

RBCs, Red blood cells; WBCs, white blood cells.

Modified from Forestier F, Daffos F, Catherine N, et al: Developmental hematopoiesis in normal human fetal blood. Blood 77:2360, 1991.

* Hematologic data obtained with a Coulter S plus II instrument. Total WBC count included nucleated red blood cells. Corrected WBC count included only WBCs, after subtracting the nucleated red cell component, based on a 100-cell manual differential.



APPENDIX 2

WBC Manual Differential Counts in Normal Fetuses at Different Gestational Ages












































Week of Gestation Lymphocytes (%) Neutrophils (%) Eosinophils (%) Basophils (%) Monocytes (%) Nucleated RBCs (% of WBCs)
18-21 (N = 186) 88 ± 7 6 ± 4 2 ± 3 0.5 ± 1 3.5 ± 2 45 ± 86
22-25 (N = 230) 87 ± 6 6.5 ± 3.5 3 ± 3 0.5 ± 1 3.5 ± 2.5 21 ± 23
26-29 (N = 144) 85 ± 6 8.5 ± 4 4 ± 3 0.5 ± 1 3.5 ± 2.5 21 ± 67
>30 (N = 172) 68.5 ± 15 23 ± 15 5 ± 3 0.5 ± 1 3.5 ± 2 17 ± 40

RBCs, Red blood cells; WBCs, white blood cells.

From Forestier F, Daffos F, Catherine N, et al: Developmental hematopoiesis in normal human fetal blood. Blood 77:2360, 1991.


APPENDIX 3

Hematologic Values for Cord Blood (Vaginal Delivery and Cesarean Section * )





























































































































Characteristic Study Sample (N = 167) Vaginal Delivery (N = 63) Cesarean Section (N = 104) P-value 2
Median Range Median Range Median Range
WBC (×10 9 per l) 15.1 5.54-39.7 18.4 12.0-34.1 13.6 8.54-39.7 <0.0001
RBC (×10 12 per l) 4.7 3.46-6.62 4.78 3.89-6.30 4.62 3.46-6.62 NS
Hb (g l −1 ) 174 130-234 176 140-230 171 130-234 NS
Hct (%) 53.6 40.1-73.1 54.7 41.9-73.1 52.6 40.1-72.2 NS
MCV (fl) 112 97.7-127 114 105-127 112 97.7-125 NS
MCH (pg) 36.5 31.4-41 36.5 31.4-41 36.6 32-39.9 NS
MCHC (g l −1 ) 324 303-359 323 308-359 324 303-344 NS
RDW (%) 17.4 14.2-23.6 17.4 14.9-23.6 17.4 14.2-23.3 NS
PLT (×10 9 per l) 270 161-607 297 169-607 254 161-424 0.0053
MPV (fl) 8.7 7.5-11.5 8.7 7.7-11.4 8.8 7.5-11.5 NS
Plateletcrit (%) 0.24 0.15-0.48 0.26 0.15-0.48 0.23 0.15-0.36 0.0056
CD34+ cells (×10 6 per l) 43.9 7.14-253 47.7 15.9-253 39.9 7.14-120 0.007

Hb, Hemoglobin; Hct, hematocrit; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; MPV, mean platelet volume; NS, not significant; plateletcrit, MPV × PLT; PLT, platelet; RBC, red blood cell; RDW, red blood cell distribution width; WBC, white blood cell.

From Eskola M, Juutistenaho S, Aranko K, et al: J Perinatol 2011; 258–262. Data obtained with Sysmex K-1000 analyzer (Sysmex, Kobe Japan).

* aP-values of the differences between vaginal delivery and cesarean section. The concentrations were standardized to exclude the varying effect of the anticoagulant.



APPENDIX 4

Hematologic Values * for Normal Cord Blood





























































Mean ± SD
Red Blood Cells
Hb (g/dL) 15.3 ± 1.3
Hct (%) 49 ± 5
RBC (×10 6 /µL) 4.3 ± 0.4
MCV (fL) 112 ± 6
MCH (pg) 36.2 ± 2.2
MCHC (g/dL) 30.9 ± 1.3
CHCM (g/dL) 30.4 ± 1.2
% HYPO (MCHC <28 g/dL) 17.3 ± 11.9
% HYPER (MCHC >41 g/dL) 0.6 ± 0.3
% MICRO (MCV <61 fL) 0.8 ± 0.3
% MACRO (MCV >120 fL) 31.8 ± 9.7
Reticulocytes
% 3.63 ± 1.11
Absolute reticulocytes (×10 9 /L) 156.1 ± 47.7
MCVr (fL) 125.8 ± 7.3
CHCMr (g/dL) 25.6 ± 1.2
CHr (pg) 31.3 ± 1.4

CHCM, Cell hemoglobin concentration mean; CHCMr, reticulocyte cell hemoglobin concentration mean; CHr, reticulocyte hemoglobin content; Hb, hemoglobin; Hct, hematocrit; % HYPER, % hyperchromic red cells; % HYPO, % hypochromic red cells; % MACRO, % macrocytic red cells; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; MCVr, reticulocyte mean corpuscular volume; % MICRO, microcytic red cells; RBC, red blood cell; SD, standard deviation.

Modified from Diagne I, Archambeaud MP, Diallo D, et al: Parametres erythrocytaires et reservés en fer dans le sang du cordon. Arch Fr Pediatr 2:208, 1995; and from G Tchernia, personal communication. Data obtained in 142 specimens with H*2 Technicon analyzer.

* Values obtained with Technicon H*2 and H*3 Hematology analyzers (Bayer Diagnostics) in neonates delivered at term with weight ≥2500 g.



APPENDIX 5

Red Cell and Reticulocyte Indices, Serum Iron Status Markers in Cord Blood







































































































Parameter Mean SD Reference Range *
Blood Count and Cellular Indices
Hb, g/L 159 15 146-189
HCT, L/L 0.49 0.05 0.44-0.58
MCV, fL 109 4 102-118
MCVr, fL 124 6 115-136
MCH, pg 35 1 33-38
MCHC, g/L 325 10 306-342
%Retic, % 4.0 0.8 2.6-5.4
IRF-H, % 24.1 7.8 10.2-40.0
CHm, pg 34.9 1.3 32.5-37.2
CHr, pg 35.6 1.3 33.1-38.6
%HYPOm, % 3.0 3.0 0.4-9.9
%HYPOr, % 42.0 15.6 18.3-76.8
Serum Measurements
TfR, mg/L 2.0 0.7 1.2-4.0
Ferritin, µg/L 198 137 45-636
TfR-F index 0.95 0.43 0.49-2.1
Iron, µmol/L 27.4 7.7 12.2-42.1
Transferrin, g/L 2.0 0.4 1.2-2.9
TfSat, % 55 19 21-111

CHm, Cellular hemoglobin in red blood cells; CHr, cellular hemoglobin in reticulocytes; Hb, hemoglobin; HCT, hematocrit; %HYPOm, percentage of hypochromic red blood cells; %HYPOr, percentage of hypochromic reticulocytes; IRF-H, high immature reticulocyte fraction; MCH, mean cell hemoglobin; MCHC, mean cell hemoglobin concentration; MCV, mean cell volume of red blood cells; MCVr, mean cell volume of reticulocytes; %Retic, proportion of reticulocytes; TfR, transferrin receptor; TfR-F index, transferrin receptor/log (ferritin); TfSat, transferrin saturation.

From Ervasti M, Kotisaari S, Sankilampi U, et al: The relationship between red blood cell and reticulocyte indices and serum markers of iron status in the cord blood of newborns. Clin Chem Lab Med 45:1000–1003, 2007. Hematologic data obtained in 199 full-term newborn infants with a ADVIA 120 analyzer (Siemens Diagnostic Solutions, Terrytown, NY).

* For reference range calculations, only samples in which Hb was greater than 146 g/L were included.



APPENDIX 6

Erythroblast and Leukocyte Counts in Umbilical Cord Blood *




















Type of Delivery Erythroblast Count (×10 9 /L) Leukocyte Count (×10 9 /L)
Spontaneous, vaginal (N = 55) 0.75 (0.0-5.3) 13.8 (7.25-48.0)
Elective cesarean section (N = 39) 0.30 (0.0-0.49) 10.6 (6.2-17.7)
Emergency cesarean section (N = 55) 1.10 (0.0-15.9) 13.5 (4.2-40.3)

From Thilaganthan B, Athansasiou S, Ozmen S, et al: Umbilical cord blood erythroblast count as an index of intrauterine hypoxia. Arch Dis Child 70:F192, 1994.

* Values are expressed as mean (range). Erythroblast counts were significantly higher in the spontaneous vaginal and emergency cesarean section groups compared with the elective cesarean group.




Appendix 7


A , Reference ranges for blood concentrations of NRBC on the day of birth are displayed according to gestational age. The lower and upper lines represent the 5% and 95% limits, and the middle line represents the mean value. B-D , Reference ranges for blood concentrations of NRBC during the first 7 days following birth are shown. The lower and upper lines represent the 5% and 95% limits, and the middle line represents the mean value. B , Reference range for neonates 1 to 36 weeks’ gestation at birth. C , Range for neonates 30 to 35 weeks’ gestation at birth. D , Range for neonates 1 to 30 weeks’ gestation at birth.

(From Christensen RD, Henry E, Andres RL et al. Reference ranges for blood concentrations of nucleated red blood cells in neonates. Neonatol 99:289–294, 2011.)





Appendix 8


Left Column , Reference ranges (5th percentile, mean, and 95th percentile) for hematocrits (top) , Hemoglobin (bottom) , both obtained during the first 6 hours after birth among patients 22 to 42 weeks gestation. Right Column (top and bottom) , Expected range of values for mean corpuscular volume (MCV, a ) and mean corpuscular hemoglobin (MCH, b ) for neonates on the first day after birth. The upper and lower boundaries incorporate 95% of the measured values.

(Left column, From Christensen RD, Henry E, Jopling J, et al: The CBC: reference ranges for neonates. Semin Perinatol 33:3–11, 2009; Right column, From Christensen RD, Jopling J Henry E et al. The erythrocyte indices of neonates, defined using data from over 12000 patients in a multihospital health care system. J Perinatol 28:24–28, 2008.)



Appendix 9


Top Left, Reference ranges for blood neutrophil concentrations during the first 72 hours after the birth of term and near-term (36 weeks’ gestation) neonates. A total of 12149 values were obtained for the analysis. The 5th percentile, the mean, and the 95th percentile values are shown. Bottom Left, Reference ranges for blood neutrophil concentration during the first 72 hours after the birth of 28 to 36 weeks’ gestation preterm neonates. A total of 8896 values were obtained for the analysis. The 5th percentile, the mean, and the 95th percentile values are shown. Top Right, Reference ranges for blood neutrophil concentration during the first 72 hours after the birth of 28 weeks’ gestation preterm neonates. A total of 852 values were obtained for the analysis. The 5th percentile, the mean, and the 95th percentile values are shown. Bottom right, Changes in polymorphonuclear neutrophils after birth in three groups with different gestational ages. Total white blood cell (WBC) counts were obtained with a Coulter S analyzer; manual differential counts were performed on 200 nucleated cells.

(Top and Bottom Left and Top Right, From Christensen RD, Henry E, Jopling J, et al: The CBC: reference ranges for neonates. Semin Perinatol 33:3–11, 2009; Bottom Right, Modified from Coulombel L, Dehan M, Tchernia G, et al: The number of polymorphonuclear leukocytes in relation to gestational age in the newborn. Acta Paediatr Scand 68:709, 1979.)


APPENDIX 10

Reference Ranges for Hb, HCt, Reticulocyte Parameters, and S-TfR During the First 15 Weeks of Life








































































































































































































































































Age, Week Hb Hct Reticulocyte CHr IRF S-TfR
Reference Interval Reference Interval Reference Interval Reference Interval Reference Interval Reference Interval
mean lower upper mean lower upper mean lower upper mean lower upper mean lower upper mean lower upper
0.5 150.5 101.8 222.4 0.45 0.30 0.65 35.7 31.5 39.9 36.6 13.5 59.7
1.5 138.7 97.9 196.3 0.41 0.29 0.58 59.5 20.2 175.6 35.0 31.1 38.9 35.5 13.7 57.2 1.4 0.9 2.4
2.5 128.8 94.0 176.5 0.38 0.28 0.52 66.8 24.7 181.1 34.3 30.6 38.1 34.3 13.6 55.1 1.3 0.8 2.3
3.5 120.6 90.0 161.5 0.36 0.27 0.47 74.1 29.2 187.9 33.7 30.1 37.4 33.3 13.1 53.4 1.3 0.8 2.1
4.5 113.8 86.2 150.3 0.34 0.26 0.44 81.2 33.7 195.8 33.1 29.5 36.7 32.2 12.4 52.1 1.2 0.7 2.0
5.5 108.3 82.5 142.1 0.32 0.25 0.42 87.9 37.8 204.3 32.6 29.0 36.2 31.3 11.6 50.9 1.2 0.7 1.9
7.0 101.9 77.8 133.7 0.30 0.23 0.39 96.7 43.1 216.7 31.9 28.3 35.5 29.9 10.3 49.6 1.1 0.7 1.8
9.0 96.9 73.5 127.7 0.29 0.22 0.38 105.2 48.4 228.8 31.2 27.5 34.8 28.4 8.6 48.1 1.1 0.7 1.8
11.0 94.9 71.7 125.7 0.28 0.21 0.37 109.0 51.3 231.9 30.6 26.9 34.3 27.0 7.4 46.7 1.1 0.7 1.9
13.0 96.1 72.6 127.3 0.28 0.21 0.37 107.6 51.4 225.2 30.2 26.5 33.9 25.9 6.7 45.0 1.2 0.7 2.0
15.0 100.5 75.9 133.1 0.30 0.22 0.39 101.2 48.1 212.9 30.0 26.4 33.6 24.9 6.7 43.3 1.3 0.8 2.2

CHr, Reticulocyte hemoglobin content; Hb, hemoglobin; Hct, hematocrit; IRF, immature reticulocyte fraction; S-Tfr, soluble transferrin receptor.

From Mäkela E, Takal TI, Suomine P, et al: Hematological parameters in preterm infants from birth to 16 weeks of age with reference to iron balance. Clin Chem Lab Med 46:551–557, 2008. Hematologic data obtained with ADVIA 120, Siemens Medical Solutions, Tarrytown, NY. S-TfR measured with an automated immunoturbidimetric methos (IDeA sTfR-IT, Orion Diagnostica), Espoo, Finland. Ferritin assayed with Elecsys ferritin electrochemiluminescence immunoassay on a Modular E analyzer (Roche Diagnostics).


APPENDIX 11

Reference Ranges for Ferritin During the First 15 Weeks of Life




































































































Age, Week Ferritin * Ferritin, No Transfusions *
Reference Interval Reference Interval
mean lower upper mean lower upper
1.5 221.4 77.0 636.8 215.5 73.5 631.6
2.5 199.9 65.6 609.2 178.5 56.9 559.8
3.5 180.4 52.8 616.5 149.2 43.9 507.2
4.5 162.8 41.4 640.2 125.9 34.1 465.4
5.5 147.0 32.3 668.4 107.2 26.8 429.7
7.0 126.0 22.6 702.3 85.7 19.2 382.1
9.0 102.6 14.9 708.7 65.7 13.3 324.6
11.0 83.5 10.6 659.1 52.3 10.1 271.7
13.0 68.0 8.2 563.0 43.2 8.3 224.0
15.0 55.3 6.9 444.8 37.0 7.5 182.9

From Mäkela E, Takal TI, Suomine P, et al: Hematologic parameters in preterm infants from birth to 16 weeks of age with reference to iron balance. Clin Chem Lab Med 46:551–557, 2008. Ferritin assayed with Elecsys ferritin electrochemiluminescence immunoassay on a Modular E analyzer (Roche Diagnostics).

* The information under the column “Ferritin” shows values calculated for the neonates who had not been transfused during the preceding 2 weeks of measurements. The information under the column “Ferritin, no transfusions” shows the values calculated for those neonates who had not been transfused at all (indicating ferritin level development in the most stable preterm neonates).



APPENDIX 12

Reference Ranges for CBC, Reticulocytes, Ferritin, and S-TfR During the First Year of Life in Preterm and Full-Term Infants













































































































































































































































































































































































































































































































Age, Weeks Hb, g/L Hct RBC count, × 10 12 /L MCV, fL MCH, pg Retic, × 10 9 /L
Mean 95% RI Mean 95% RI Mean 95% RI Mean 95% RI Mean 95% RI Mean 95% RI
Preterm
20 112.2 92.0-136.8 0.327 0.271-0.395 4.03 3.15-4.92 81.6 73.2-90.0 28.1 25.2-31.0 77.4 39.0-153.5
25 116.8 98.7-138.1 0.340 0.287-0.401 4.27 3.48-5.07 80.1 72.3-88.0 27.7 24.8-30.5 69.7 36.7-132.5
30 120.8 103.6-140.9 0.351 0.300-0.411 4.47 3.70-5.25 79.0 71.2-86.7 27.3 24.4-30.3 64.1 34.3-119.6
35 124.3 106.7-144.7 0.360 0.309-0.421 4.64 3.83-5.44 78.1 70.1-86.0 27.1 24.0-30.2 60.1 32.4-111.8
40 127.0 108.5-148.6 0.368 0.315-0.431 4.76 3.92-5.60 77.5 69.3-85.7 26.9 23.7-30.1 57.6 30.9-107.2
45 129.0 109.6-151.8 0.374 0.319-0.438 4.85 3.98-5.71 77.3 68.9-85.6 26.8 23.5-30.0 56.3 30.1-105.1
50 130.2 110.3-153.6 0.378 0.323-0.442 4.89 4.03-5.75 77.3 69.0-85.6 26.7 23.6-29.9 56.1 30.0-105.2
55 130.6 111.1-153.6 0.380 0.326-0.442 4.90 4.07-5.73 77.6 69.6-85.7 26.8 23.7-29.8 57.2 30.3-107.7
60 130.2 112.0-151.3 0.379 0.329-0.437 4.87 4.11-5.62 78.2 70.7-85.8 26.9 24.0-29.7 59.4 31.1-113.5
Full-Term
20 120.0 102.2-140.9 0.345 0.293-0.407 4.32 3.76-4.87 80.3 74.2-86.4 27.9 25.6-30.2 45.5 25.3-82.2
25 118.9 101.9-138.8 0.345 0.296-0.402 4.38 3.84-4.92 79.0 73.1-84.9 27.3 24.9-29.6 45.2 25.1-81.5
30 118.3 101.5-137.7 0.345 0.298-0.400 4.44 3.90-4.98 78.1 72.3-83.9 26.8 24.3-29.2 45.4 26.1-78.9
35 118.0 101.5-137.3 0.346 0.300-0.400 4.48 3.93-5.03 77.6 71.8-83.4 26.5 23.9-29.0 46.0 27.6-76.6
40 118.2 102.0-137.1 0.348 0.303-0.400 4.51 3.96-5.06 77.4 71.6-83.2 26.3 23.7-28.9 47.1 28.8-76.8
45 118.9 102.9-137.3 0.351 0.307-0.401 4.54 3.99-5.08 77.6 71.7-83.5 26.3 23.6-29.0 48.7 28.7-82.5
50 120.0 104.2-138.1 0.354 0.313-0.402 4.55 4.01-5.08 78.2 72.2-84.1 26.5 23.8-29.2 50.9 26.9-96.3
55 121.5 105.4-140.0 0.359 0.319-0.403 4.55 4.04-5.06 79.1 73.1-85.1 26.9 24.2-29.6 53.7 23.9-121.0
Age, Weeks Ferritin, µg/L S-TfR, mg/L CHr, pg WBC count, × 10 9 /L Platelet count, × 10 9 /L
Mean 95% RI Mean 95% RI Mean 95% RI Mean 95% RI Mean 95% RI
Preterm
20 37.8 7.37-193.9 1.52 1.07-2.16 29.8 26.6-33.1 9.48 5.63-16.0 478 294-777
25 30.1 7.48-120.8 1.54 1.10-2.15 29.6 26.4-32.8 9.60 5.73-16.1 465 290-744
30 24.7 7.06-86.6 1.56 1.12-2.16 29.4 26.2-32.7 9.71 5.82-16.2 452 286-714
35 21.1 6.41-69.5 1.57 1.14-2.17 29.3 26.0-32.6 9.83 5.92-16.3 439 280-687
40 18.6 5.80-59.9 1.59 1.16-2.19 29.2 25.9-32.6 9.94 6.01-16.5 427 274-663
45 17.1 5.41-53.8 1.61 1.17-2.21 29.2 25.8-32.6 10.1 6.09-16.6 415 268-642
50 16.2 5.25-49.8 1.63 1.18-2.25 29.3 25.8-32.7 10.2 6.17-16.8 403 260-623
55 15.9 5.31-47.5 1.65 1.18-2.30 29.4 25.8-32.9 10.3 6.24-17.0 391 252-607
60 16.2 5.44-47.9 1.67 1.18-2.36 29.5 25.9-33.2 10.4 6.31-17.2 380 244-593
Full-Term
20 71.7 21.5-239.7 1.49 1.06-2.08 29.8 27.4-32.1 9.36 5.84-15.0 426 282-646
25 51.1 16.1-162.2 1.52 1.08-2.12 29.2 25.7-32.6 9.19 5.73-14.7 415 269-640
30 38.5 11.5-128.7 1.54 1.09-2.19 28.8 24.7-32.9 9.02 5.57-14.6 404 258-634
35 30.6 8.76-107.0 1.57 1.09-2.27 28.7 24.5-32.9 8.85 5.37-14.6 394 247-628
40 25.8 7.46-89.1 1.60 1.08-2.37 28.9 25.1-32.6 8.68 5.14-14.7 383 237-621
45 22.9 7.01-75.0 1.63 1.07-2.48 29.2 26.4-32.1 8.52 4.88-14.9 373 227-614
50 21.6 6.78-68.6 1.66 1.05-2.62 29.9 27.6-32.2 8.36 4.61-15.2 363 218-607
55 21.5 5.90-78.0 1.69 1.04-2.76 30.8 27.0-34.5 8.21 4.33-15.5 354 209-599

CBC, Complete blood count; CHr, reticulocyte hemoglobin content; Hb, hemoglobin; Hct, hematocrit; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; RBC, red blood cell; Retic, reticulocyte; RI, reference interval; S-Tfr, soluble transferrin receptor; WBC, white blood cell.

From Takale TI, Mäkela E, Suomine P, et al: Blood Cell and iron status analytes of preterm and full-term infants from 20 weeks onward during the first year of life. Clin Chem Lab Med 48:1295–1301, 2010. Hematologic data obtained with ADVIA 120, Siemens Medical Solutions, Tarrytown, NY. S-TfR measured with an automated immunoturbidimetric methos (IDeA sTfR-IT, Orion Diagnostica), Espoo, Finland. Ferritin assayed with Elecsys ferritin electrochemiluminescence immunoassay on a Modular E analyzer (Roche Diagnostics).



Appendix 13

From Cembrowski GS, Chan J, Cheng C, Bamforth FJ. NHANES 1999-2000 Data used to create comprehensive health-associated race-, sex-, and age-stratified pediatric reference intervals for the Coulter MAXM. Lab Hematol 10:245–246, 2004. Presented at the annual meeting of the International Society for Laboratory Hematology, Barcelona, Spain, May 2004. Numerical summary kindly provided by GS Cembrowski, MS Cembrowski, KA Versluys, 2013. Original Graphs at www.mylaboratoryquality.com/hematologyri1x.htm .



Appendix 14


Hb and MCV percentile curves for African American and Mexican American/Caucasian girls and boys. Top row, Hb percentile curves for African American girls and boys and for Mexican American and Caucasian girls and boys. Bottom row, MCV percentile curves for African American girls and boys and for Mexican American and Caucasian girls and boys.

(From Cembrowski GS, Chan J, Cheng C, Bamforth FJ: NHANES 1999-2000 Data used to create comprehensive health-associated race-, sex-, and age-stratified pediatric reference intervals for the Coulter MAXM. Lab Hematol 10:245–246, 2004. Presented at the annual meeting of the International Society for Laboratory Hematology, Barcelona, Spain, May 2004. Numerical summary kindly provided by GS Cembrowski, MS Cembrowski, KA Versluys, 2013. Original Graphs at www.mylaboratoryquality.com/hematologyri1x.htm . )



Appendix 15

From Cembrowski GS, Chan J, Cheng C, Bamforth FJ. NHANES 1999-2000 Data used to create comprehensive health-associated race-, sex-, and age-stratified pediatric reference intervals for the Coulter MAXM. Lab Hematol 10:245–246, 2004. Presented at the annual meeting of the International Society for Laboratory Hematology, Barcelona, Spain, May 2004. Numerical summary kindly provided by GS Cembrowski, MS Cembrowski, KA Versluys, 2013. Original Graphs at www.mylaboratoryquality.com/hematologyri1x.htm .


APPENDIX 16

Reference Ranges for WBC, Hb, Hct, and MCV in African-American Children and Adolescents *









































































African-American
[Hb (g/dL)]
African-American
[Hct (%)]
African-American
[MCV (fl)]
Age (years) African American (mean WBC) Mean −2 STD Mean −2 STD Mean −2 STD
2-5 7.33 11.94 10.37 35.98 31.54 79.81 74.65
6-10 6.74 12.44 10.3 37.27 32.71 81.44 76.45
11-15 male 6.32 13.2 10.97 39.29 32.91 83.20 77.99
11-15 female 6.58 12.67 10.1 37.95 33.41 83.60 78.01
16-18 male 5.91 14.35 11.30 43.50 37.62 86.02 80.85
16-18 female 6.92 12.55 10.27 37.39 31.87 85.26 79.43

Hb, Hemoglobin; Hct, hematocrit; MCV, mean corpuscular volume; STD, standard deviation; WBC, white blood cell.

From Robins EB, Blum S: Hematologic reference values for African American children and adolescents. Am J Hematol 82:611–614, 2007.

* Sample size is 5039. Mean values obtained from NHANES (National Health and Nutrition Examination Survey) and Robins studies.



APPENDIX 17

WBC and ANC Mean Values and Reference Intervals *



































































































12-18 Years: WBC >18 Years: WBC 12-18 Years: ANC >18 Years: ANC
N N N N
NHBM 401 3.2-9.3 (5.6) 547 3.1-9.9 (6.1) 401 1.0-6.2 (2.9) 547 1.3-6.6 (3.1)
MAM 493 4.1-11.4 (6.9) 776 4.1-11.4 (7.1) 492 1.8-8.2 (4.1) 776 2.1-7.9 (4.2)
NHWM 342 4.1-11.4 (6.8) 1473 4.1-11.8 (7.0) 342 1.8-7.2 (3.8) 1471 2.1-8.0 (4.3)
MAM, NHWM 835 4.1-11.4 (6.8) 2249 4.1-11.6 (7.1) 834 2247 2.1-8.0 (4.3)
NHBF 329 3.7-10.1 (6.2) 344 3.4-11 (6.3) 329 1.2-6.6 (3.1) 344 1.4-7.5 (3.4)
MAF 401 4.1-12.0 (7.6) 552 4.5-11.8 (7.5) 401 1.9-8.4 (5.3) 550 2.2-8.0 (4.9)
NHWF 322 4.1-11.3 (7.2) 1222 3.9-11.6 (7.0) 322 1.9-7.7 (4.0) 1221 2.0-7.9 (4.7)
MAF, NHWF 723 1774 723 1771 2.0-7.9 (4.8)

ANC, Absolute neutrophil count; MAF, female Mexican American; MAM, male Mexican American; NHBF, female non-Hispanic black; NHBM, male non-Hispanic black; NHWF, female non-Hispanic white; NHWM, male non-Hispanic white; WBC, white blood cell.

From Lim EM, Cembrowski G, Cembrowski M, et al: Race-specific WBC and neutrophil count reference intervals. J Lab Clin Hematol 32:590–597, 2010.

* Data are presented as reference intervals (2.5-97.5 percentile limits) and mean values (in parentheses).


Could not be pooled because of variation within and between populations.



APPENDIX 18

Activities of RBC Enzymes



















































































































Enzyme Activity at 37° C (mean ± SD)
Acetylcholinesterase 36.93 ± 3.83
Adenosine deaminase 1.11 ± 0.23
Adenylate kinase 258 ± 29.3
Aldolase 3.19 ± 0.86
Bisphosphoglyceromutase (2,3- diphosphoglyceromutase) 4.78 ± 0.65
Catalase 15.3 ± 2.4 × 10 4
Enolase 5.39 ± 0.83
Epimerase 0.23 ± 0.06
Galactokinase 0.029 ± 0.004
Galactose-1-phosphate uridyltransferase 28.4 ± 6.94
Glucose phosphate isomerase 60.8 ± 11.0
Glucose-6-phosphate dehydrogenase 8.34 ± 1.59
WHO method 12.1 ± 2.09
Glutamic oxaloacetic transaminase without PLP 3.02 ± 0.67
Glutamic oxaloacetic transaminase with PLP 5.04 ± 0.90
γ-Glutamylcysteine synthetase 0.43 ± 0.04
Glutathione peroxidase 30.82 ± 4.65
Glutathione reductase without FAD 7.18 ± 1.09
Glutathione reductase with FAD 10.4 ± 1.50
Glutathione S-transferase 6.66 ± 1.81
Glyceraldehyde phosphate dehydrogenase 226 ± 41.9
Hexokinase 1.78 ± 0.38
Hypoxanthine phosphoribosyltransferase 1.72 ± 0.30
Lactate dehydrogenase 200 ± 26.5
Methemoglobin reductase 2.60 ± 0.71
Monophosphogylceromutase 37.71 ± 5.56
NADH-methemoglobin reductase 19.2 ± 3.85 (30°)
NADPH diaphorase 2.26 ± 0.16
Phosphofructokinase 11.01 ± 2.33
Phosphoglucomutase 5.50 ± 0.62
Phosphoglycerate kinase 320 ± 36.1
Phosphoglycolate phosphatase 1.23 ± 0.10
Pyrimidine 5′ nucleotidase 0.11 ± 0.03
Pyruvate kinase 15.0 ± 1.99
6-Phosphogluconate dehydrogenase 8.78 ± 0.78
Triose phosphate isomerase 2111 ± 397

FAD, Flavin adenine dinucleotide; NADH, reduced nicotinamide adenine dinucleotide; NADPH, reduced nicotinamide adenine dinucleotide phosphate; PLP, pyridoxal 5-phosphate; SD, standard deviation; WHO, World Health Organization.

From Beutler E, Blum KG: In Altman PL, Dittmer DS, editors: Human health and disease. Bethesda, Md., Federation of American Societies for Experimental Biology, 1977, p. 156; and Beutler E: Red cell metabolism: a manual of biochemical methods, 3 rd ed, Orlando, Fla., Grune & Stratton, 1984.


APPENDIX 19

Levels of Intermediate Metabolites in Normal Adult Erythrocytes












































































































Metabolite CONCENTRATION (mean ± 1 SD)
Abbreviation nmol/g Hb nmol/mL Red Cells µmol/L in Whole Blood
Adenosine-5′-diphosphate ADP 6635 ± 105 216 ± 36
Adenosine-5-monophosphate AMP 62 ± 10 21.1 ± 3.4
Adenosine-5-triphosphate ATP 4230 ± 290 (whites)
3530 ± 301 (blacks)
1438 ± 99
1200 ± 102
2,3-Diphosphoglycerate 2,3-DPG 1227 ± 1870 4171 ± 636
Glutathione GSH 6570 ± 1040 2234 ± 354
Glutathione (oxidized) GSSG 12.3 ± 4.5 4.2 ± 1.53
Glucose-6-phosphate G6P 82 ± 22 27.8 ± 7.5
Fructose-6-phosphate F6P 27 ± 5.8 9.3 ± 2.0
Fructose-6-diphosphate FDP 5.6 ± 1.8 1.9 ± 0.6
Dihydroxyacetone phosphate DHAP 27.6 ± 8.2 9.4 ± 2.8
3-Phosphoglyceric acid 3-PGA 132 ± 15.0 44.9 ± 5.1
2-Phosphoglyceric acid 2-PGA 21.5 ± 7.35 7.3 ± 2.5
Phosphoenolpyruvate PEP 35.9 ± 6.47 12.2 ± 2.2
Creatine 1310 ± 310 (male)
1500 ± 250 (female)
445 ± 105
510 ± 85
Lactate 932 ± 211
Pyruvate 53.3 ± 21.5

SD, Standard deviation.

From Beutler E : Red cell metabolism: a manual of biochemical methods, 3rd ed. Orlando, Fla., 1984, Grune & Stratton.


APPENDIX 20

Red Cell Enzyme Activity in Premature and Term Neonates, Adults, and Adult Reticulocytes






























































































Premature Infants (N = 11) Term Infants (N = 10) Normal Adults (N = 50) 95% Adult *
Reticulocytes
Hexokinase (HK) 3.6 ± 0.6 a 2.7 ± 0.3 a 1.15 ± 0.35 9.9 a
Glucosephosphate isomerase (PGI) 94.5 ± 15.2 a 88 ± 16 a 67.7 ± 12.0 95.7 c
Phosphofructokinase (PFK) 8.0 ± 1.3 d 7.1 ± 1.5 c 8.4 ± 3.4 14.1 d
Aldolase (ALD) 4.3 ± 0.8 c 5.3 ± 1.7 b 3.55 ± 1.07 9.5 a
Triosephosphate isomerase (TIM) 2961 ± 1378 d 1787 ± 380 d 2700 ± 700 3220 d
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) 131 ± 76 d 164 ± 45 d 134 ± 93 240 d
Phosphoglycerate mutase (PGK) 591 ± 114 b 436 ± 119 b 312 ± 86 438 d
Diphosphoglycerate mutase (DPGM) 8.3 ± 3.6 c 6.7 ± 1.9 c 5.3 ± 2.5 7.3 d
Enolase (ENO) 15.1 ± 3.4 a 14.6 ± 2.1 a 7.8 ± 2.2 8.1 d
Pyruvate kinase (PK) 19.4 ± 3.5 a 17.3 ± 2.5 a 11.4 ± 2.8 54.2 a
Glucose-6-phosphate dehydrogenase (G6PD) 21.3 ± 3.8 a 19.1 ± 4.3 a 10.9 ± 3.8 30.6 a
6-Phosphogluconate dehydrogenase (6PGD) 9.1 ± 2.1 d 9.9 ± 1.6 c 8.4 ± 1.0 14.4 a
Glutathion reductase (GR) 9.5 ± 1.7 a 11.0 ± 2.6 a 7.2 ± 2.2 11.3 c
Acetyl choline esterase (ACE) 17.5 ± 3.5 a 18.5 ± 4.1 a 36.9 ± 3.8 44.4 c

From Jansen G, Koenderman L, Rijksen G, et al: Characteristics of hexokinase, pyruvate kinase, and glucose-6-phosphate dehydrogenase during adult and neonatal reticulocyte maturation. Am J Hematol 20:203–215, 1985.

* Obtained after Percoll density gradient centrifugation of red cells from a patient with a hemolytic syndrome. Statistical interpretation versus normal adult group: P <.001; P <.01; P <.1; not significant.



APPENDIX 21

Red Cell Glycolytic Intermediate Metabolites in Normal Adults, Term Infants, and Premature Infants *






































































Metabolite Normal Adults (10) Term Infants (10) Premature Infants (11) Normals (5)
Glucose-6-phosphate 24.8 ± 9.8 45.2 ± 8.7 66.8 ± 34.8 27 ± 2.4
Fructose-6-phosphate 5.4 ± 1.0 9.9 ± 2.3 20.5 ± 8.9 11 ± 2.5
Fructose, 1,6-diphosphate 4.6 ± 1.0 3.8 ± 0.7 3.6 ± 0.8 5 ± 0.9
Dihydroxyacetone phosphate 4.9 ± 3.5 11.9 ± 5.0 18.6 ± 10.7 12 ± 3.7
Glyceraldehyde-3-phosphate 2.6 ± 0.7 1.9 ±1.6 6.5 ± 3.2 4 ± 1.5
3-Phosphoglycerate 61.6 ± 12.4 58.2 ± 14.4 47.5 ± 14.2 48 ± 16.1
2-Phosphoglycerate 4.3 ± 1.8 4.9 ± 1.6 4.4 ± 2.5 7 ± 1.7
Phosphoenolpyruvate 8.8 ± 2.6 7.6 ± 2.9 7.4 ± 3.0 12 ± 0.9
Pyruvate 73.5 ± 33.1 70.4 ± 32.3 78.4 ± 4.15 71 ± 17.7
2,3-Diphosphoglycerate 4423 ± 1907 3609 ± 800 3152 ± 2133 4000

From Oski FA: Red cell metabolism in the newborn infant: V. Glycolytic intermediates and glycolytic enzymes. Pediatrics 44:87, 1969.

* Infant samples were obtained from newborns weighing more than 2800 g whose gestational age was 39 weeks or greater. Blood was drawn within 24 hours of birth. All the newborns were clinically healthy. Adult samples were obtained from healthy normal volunteers.



APPENDIX 22

RBC Enzyme Activity * in ELBWI Infants and Premature and Normal Adults (Whole Blood and Reticulocyte Rich)












































































































































































Normal Adult
(N = 28)
Mean ± SD
ELBWI
(N = 28)
Mean ± SD
Reticulocyte Rich
(N = 20)
Mean ± SD
ELBWI
Versus
Reticulocyte Rich
ELBWI
Versus
Normal Adults
Hexokinase (HK) 1.05 ± 0.11 3.28 ± 0.47 3.45 ± 1.78 NS High ( P <.0001)
Glucosephosphate isomerase (GPI) 58.4 ± 5.0 83.4 ± 6.2 65.2 ± 8.5 High ( P <.0001) High ( P <.0001)
Phosphofructokinase (PFK) 13.3 ± 1.7 10.1 ± 1.6 15.8 ± 2.4 Low ( P <.0001) Low ( P <.0001)
Aldolase (ALD) 3.09 ± 0.53 4.73 ± 5.13 5.12 ± 0.94 NS High ( P <.0001)
Triosephosphate isomerase (TPI) 1760 ± 253 2215 ± 339 2077 ± 375 NS High ( P <.0001)
Glyceraldehyde-3-phosphate dehydrogenase (GA3PD) 191 ± 34 252 ± 39 232 ± 51 NS High ( P <.0001)
Phosphoglycerate kinase (PGK) 288 ± 31 469 ± 67 355 ± 43 High ( P <.0001) High ( P <.0001)
Monophosphoglycerate mutase (MPGM) 23.5 ± 2.8 33.8 ± 6.9 29.9 ± 5.3 High ( P = .0412) High ( P <.0001)
Enolase (ENL) 6.9 ± 1.0 23.9 ± 3.0 9.3 ± 1.7 High ( P <.0001) High ( P <.0001)
Pyruvate kinase (PK) 16.3 ± 2.1 29.7 ± 4.0 27.6 ± 8.1 NS High ( P <.0001)
Lactate dehydrogenase (LDH) 195 ± 17 248 ± 28 264 ± 34 NS High ( P <.0001)
Glucose-6-phosphate dehydrogenase (G6PD) 7.6 ± 0.8 18.1 ± 2.2 12.8 ± 2.0 High ( P <.0001) High ( P <.0001)
6-Phosphogluconate dehydrogenase (6PGD) 8.1 ± 1.0 8.2 ± 1.5 13.2 ± 1.8 Low ( P <.0001) NS
Glutathione reductase (GR) 7.1 ± 1.2 9.2 ± 1.8 7.8 ± 1.8 High ( P = .0090) High ( P <.0001)
GR + flavin adenine dinucleotide (FAD) 9.9 ± 1.6 b 10.9 ± 1.7 b 10.4 ± 1.7 NS NS
Glutathione peroxidase (GSH-Px) 31.8 ± 5.7 22.5 ± 4.0 41.3 ± 7.4 Low ( P <.0001) Low ( P <.0001)
Adenylate kinase (AK) 252 ± 35 132 ± 18 253 ± 26 Low ( P <.0001) Low ( P <.0001)
Adenosine deaminase (ADA) 1.25 ± 0.33 0.96 ± 0.30 1.60 ± 0.60 Low ( P <.0001) Low ( P = .0010)
Acetylcholinesterase (AchE) 31.7 ± 4.7 16.7 ± 3.3 37.6 ± 10.1 Low ( P <.0001) Low ( P <.0001)
Pyrimidine 5′-nucleotidase 9.1 ± 1.4 17.0 ± 4.0 19.1 ± 4.5 ns High ( P <.0001)
NADH methemoglobin reductase (MetHbR) 14.9 ± 1.8 b 11.5 ± 2.1 a 14.1 ± 2.3 a Low ( P = .0087) Low ( P <.0001)
Catalase (CAT) 13.6 ± 2.1 b 11.8 ± 2.7 a 15.6 ± 3.2 a Low ( P = .0048) Low ( P = .0459)
Reduced glutathione (GSH) (mg/dL RBC) 67.8 ± 9.3 76.9 ± 13.8 69.4 ± 12.0 NS High ( P = .0059)

ELBWI, Extremely low-birth-weight infants (birth weight <1000 g); Hb, hemoglobin; NS, not significant; RBC, red blood cell; SD, standard deviation.

From Miyazono Y, Hirono A, Miyamoto Y, et al: Erythrocyte enzyme activities in cord blood of extremely low-birth-weight infants. Am J Hematol 62:88–92, 1999.

* All enzyme activities are represented as units/g Hb, except for CAT (10 4 units/g Hb) and P5N (µmol Pi liberated/hr/g Hb). N = 12; N = 20.



APPENDIX 23

G6PD Reference Values for G6PD-Normal and –Deficient Males and Females with Probable Genotypes




































































Category (U/g Hb) No. Median Value IQR Min-Max G6PD Phenotype Probable Genotype *
Male (N = 1502)
<7.0 243 (16.2%) 0.28 0.21-0.39 0.01-6.20 Deficient Deficient hemizygote
≥9.0 1256 (83.8%) 18.76 17.27-21.68 9.00-34.66 Normal Normal hemizygote
Female (N = 1298)
<7.0 81 (6.2%) 4.84 0.45-6.16 0.06-6.96 Deficient Deficient homozygote
7.0-9.4 64 (4.9%) 8.61 7.67-9.00 7.04-9.46 Intermediate Heterozygote
≥9.5 1153 (88.8%) 18.36 16.21-20.63 9.54-35.50 Normal Normal homozygote

* In females, because of nonrandom X chromosome inactivation among heterozygotes, accurate genotype categories may be difficult to determine based on phenotype. The term “probable” genotype is therefore used.


Male genotype based on phenotype may be assumed with reasonable accuracy.



APPENDIX 24

Hemoglobin A Content in Male and Female Newborns According to Birth Weight








































Birth Weight (g) Males Hb A (%) Females Hb A (%)
<1501 7.1 ± 1.3 (9) 13.2 ± 11.3 (14)
1501-2000 12.2 ± 8.2 (36) 13.1 ± 10.4 (44)
2001-2500 12.6 ± 5.2 (139) 14.9 ± 6.5 (206) *
2501-3000 15.8 ± 6.4 (635) 17.8 ± 6.2 (776) *
3001-3500 18.2 ± 6.5 (1289) 19.9 ± 6.8 (1204) *
3501-4000 20.0 ± 6.6 (803) 20.9 ± 7.2 (590) *
4001-4500 19.7 ± 6.3 (200) 22.6 ± 8.6 (94) *
>4500 21.7 ± 7.0 (45) 20.9 ± 7.2 (20)

HbA, Hemoglobin A.

From Galacteros F, Guilloud-Bataille M, Feingold J: Sex, gestational age, and weight dependency of adult hemoglobin concentration in normal newborns. Blood 78:1121, 1991.

* P <.05 between male and female newborns.




Appendix 25


Relative concentration of hemoglobin F in infants and its variation with age. The region between the curved lines contains 120 observations in 17 normal children.

(From Garby L, Sjolin S. Development of erythropoiesis. Acta Paediatr 51:245, 1962.)


APPENDIX 26

Percentage of Hemoglobins F and A2 in the Newborn and Adult *
















% Hb F (Gα : Aα ratio) % Hb A2
Newborn 60-90 (3 : 1) <1.0
Adult <1.0 (2 : 3) 1.6-3.5

Hb, Hemoglobin.

From Altman PL, Dittmer DS, editors: Human health and disease. Bethesda, MD, 1977, Federation of American Societies for Experimental Biology, p. 159.

* The α chains of fetal hemoglobin contain either a glycyl residue or an alanyl residue at position 136. The Gα : Aα ratio in the newborn undergoes a considerable change between the third and fourth months of life, at which time it approximates that of the Hb F of adults.



APPENDIX 27

Methemoglobin Levels in Normal Children *



















































































































METHEMOGLOBIN (g/dL) METHEMOGLOBIN AS PERCENTAGE OF TOTAL HEMOGLOBIN
No. Cases No. Det. Mean Range Standard Dev. No. Cases No. Det. Mean Range Standard Dev.
Prematures (birth-7 days) 29 34 0.43 (0.02-0.83) ±0.07 24 28 2.3 (0.08-4.4) ±1.26
Prematures (7-72 days) 21 29 0.31 (0.02-0.78) ±0.19 18 23 2.2 (0.02-4.7) ±1.07
Prematures (total) 50 63 0.38 (0.02-0.83) ±0.10 42 51 2.2 (0.08-4.7) ±1.10
Cook County Hospital, prematures (1-14 days) 8 8 0.52 (0.18-0.83) ±0.08
Newborns (1-10 days) 39 39 0.22 (0.00-0.58) ±0.17 25 30 1.5 (0.00-2.8) ±0.81
Infants (1 month-1 year) 8 8 0.14 (0.02-0.29) ±0.09 8 8 1.2 (0.17-2.4) ±0.78
Children (1-14 years) 35 35 0.11 (0.00-0.33) ±0.09 35 35 0.79 (0.00-2.4) ±0.62
Adults (14-78 years) 30 30 0.11 (0.00-0.28) ±0.09 27 27 0.82 (0.00-1.9) ±0.63

From Kravitz H, Elegant LD, Kaiser E, et al: Methemoglobin values in premature and mature infants and children. Am J Dis Child 91:2, 1956.

* The premature and full-term infants were free of known disease. None had respiratory distress or cyanosis. Analysis of milk and water ingested by these infants revealed a nitrate level less than 0.027 ppm. The premature infants routinely received vitamin C orally each day from the seventh day of life.



APPENDIX 28

Hemoglobin, Serum Transferrin Saturation, Serum Ferritin * , and Red Cell Indices in Adolescents (15-16 Years of Age)






















































































































PERCENTILE
Mean ± SD 10th 25th 50th 75th 90th
Boys
Hb (g/dL) 14.7 ± 0.831 135 14.2 14.7 15.2 15.7
Transferrin saturation (%) 32.7 ± 10.25 21.2 25.7 31.7 38.6 46.3
Serum ferritin (µg/L) 26.4 ± 17.71 13.2 22 29 40.8 52
MCV (fL) 88.4 ± 3.87 83.5 85.5 88.1 90.9 93.2
RDW (%) 13.0 ± 0.95 12.3 12.5 12.9 13.2 13.5
MCH (pg) 29.4 ± 1.43 27.7 28.6 29.2 30.2 31.0
Girls
Hb (g/dL) 13.4 ± 0.763 12.3 12.9 13.4 13.9 14.3
Transferrin saturation (%) 29.9 ± 10. 7 17.2 22.8 29 35.2 43.4
Serum ferritin (µg/L) 18.2 ± 1.98 7.5 12 18.2 28.5 41.5
MCV (fL) 90.1 ± 3.86 84.8 87.6 90.3 92.8 94.8
RDW (%) 12.8 ± 0.71 12.1 12.4 12.7 13.2 13.6
MCH (pg) 29.6 ± 1.43 27.8 28.8 29.5 30.6 31.3

Hb, Hemoglobin; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; RDW, red blood cell volume distribution width; SD, standard deviation.

From Hallberg L, Hulten L, Lindstedt G, et al: Prevalence of iron deficiency in Swedish adolescents. Pediatr Res 34:680–687, 1993.

* Data for serum ferritin are presented as geometric means ± antilog of logarithmic values.


Data collected in 197 to 207 boys and 215 to 220 girls, from ages 15 to 16.



APPENDIX 29

Hemoglobin and Iron Status Indicators According to Age






















































































































2 m 6 m 9 m
Mean ± SD 5-95 Percentiles N Mean ± SD 5-95 Percentiles N Mean ± SD 5-95 Percentiles N
Hemoglobin
(g/L) 115 ± 8 101-130 68 116 ± 9 105-130 57 117 ± 7 103-129 94
(mmol/L) 7.1 ± 0.5 6.3-8.1 7.2 ± 0.6 6.5-8.1 7.3 ± 0.5 6.4-8
Serum ferritin * (µg/L) 301 134-675 63 59 23-140 54 37 17-78 84
Erythrocyte protoporphyrin (nmol/l erythrocytes) 679 ± 185 479-1148 65 475 ± 109 304-659 48 556 ± 133 369-763 83
Serum transferrin (µmol/L) 26 ± 4 20-33 65 31 ± 4 24-38 57 35 ± 7 26-47 90
Serum iron (µmol/L) 13.1 ± 3.5 7.5-19.1 59 9.9 ± 3.1 6.3-17.3 46 8.8 ± 3.4 3.9-14.9 80
Transferrin saturation (%) 26 ± 8 15-40 59 16 ± 6 10-29 46 13 ± 6 5-25 77
Mean red cell volume (fl) 86 ± 5 78-94 64 76 ± 4 69-82 49 76 ± 6 68-85 89

m , Months; SD , standard deviation.

From Michaelsen KF, Milman N, Samuelson G: A longitudinal-study of iron status in healthy Danish infants—effects of early iron status, growth velocity and dietary factors. Acta Paediatr 84:1035–44, 1995.

* Geometric mean values.


Significantly different ( P <.001) from values at 6 months (Student’s paired t -test).



APPENDIX 30

Serum Ferritin, Iron, Total Iron-Binding Capacity, and Transferrin Saturation in Children and Adolescents

























































































































































































































































































Age Male Subjects Female Subjects
Ferritin ng/mL µg/L ng/mL µg/L
1-30 d * 6-400 6-400 6-515 6-515
1-6 m * 6-410 6-410 6-340 6-340
7-12 m * 6-80 6-80 6-45 6-45
1-5 y 6-24 6-24 6-24 6-24
6-9 y 10-55 10-55 10-55 10-55
10-14 y 23-70 23-70 6-40 6-40
14-19 y 23-70 23-70 6-40 6-40
Iron µg/dL µmol/L µg/dL µmol/L
1-5 y 22-136 4-25 22-136 4-25
6-9 y 39-136 7-25 39-136 7-25
10-14 y 28-134 5-24 45-145 8-26
14-19 y 34-162 6-29 28-184 5-33
Iron-Binding Capacity
1-5 y 268-441 48-79 268-441 48-79
6-9 y 240-508 43-91 240-508 43-91
10-14 y 302-508 54-91 318-575 57-103
14-19 y 290-570 52-102 302-564 52-101
Transferrin Saturation
1-5 y 0.07-0.44 0.07-0.44
6-9 y 0.17-0.42 0.17-0.42
10-14 y 0.11-0.36 0.02-0.40
14-19 y 0.06-0.33 0.06-0.33
Transferrin U/L (Males and Females)
0-5 d § 1.43-4.46
1-3 y § 2.18-3.47
4-6 y § 2.08-3.78
7-9 y § 2.25-3.61
10-13 y § 2.24-4.42
14-19 y § 2.33-4.44

d, Days; m, months; y, years.

* Soldin SJ, Morales A, Albalos F, et al: Pediatric reference ranges on the Abbott IMx for FSH, LH, prolactin, TSH, T 4, T 3 , free T3, T-uptake, IgE, and ferritin. Clin Biochem 28:603, 1995. Study based on hospitalized patients; values represent 2.5th and 97.5th percentiles.


No significant differences between males and females; range derived from combined data.


Lockitch, G; Halstead, AC; Wadsworth, et al: Age- and sex-specific pediatric reference intervals and correlations for zinc, copper, selenium, iron, vitamins A and E, and related proteins. Clin Chem 34:1625, 1988. Study based on healthy children; values represent the 0.025 and 0.975 fractiles. Transferrin saturation calculated from iron (µmol/L)/total iron binding capacity. Note that the lower reference limits for serum iron and transferrin saturation in this study are below the limits used to define acceptable levels for these two analytes (O’Neal RM, Johnson OC, Schaefer AE: Guidelines for classification and interpretation of group blood and urine data collected as part of the National Nutrition Survey. Pediatr Res 4:103, 1970.)


§ Lockitch, G; Halstead, AC; Quigley G, et al: Age- and sex-specific pediatric reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN nephelometer. Clin Chem 34:1618, 1988. Results are 2.5th and 97.5 percentiles.



APPENDIX 31

Reference Ranges for Erythrocyte Zinc Protoporphyrin in Children and Adolescents
































































Age Groups Blood ZPP Reference Ranges 2.5th–97.5th Percentiles (µg/dL) * Blood ZPP Reference Ranges 2.5th–97.5th Percentiles (µmol/mol heme) N
Males Females Males Females Males Females
0-12 months 8.5-34.5 9-40 15.6-63.5 16.6-73.6 145 203
13-24 months 10-34 11-32 18.4-62.6 20.2-58.9 605 725
2-5 years 5-35 10-31 9.2-64.4 18.4-57.0 1926 1822
6-9 years 6-31 9-30 11.0-57.0 16.6-55.2 522 408
10-17 years 5.5-31.5 5-33.5 10.1-58.0 9.2-61.6 61 61
Total 3259 3219

ZPP, Zinc protoporphyrin.

From Soldin OP, Miller M, Soldin SJ: Pediatric reference ranges for zinc protoporphyrin. Clin Biochem 36:21–25, 2003.

* Multiply µg/dL by 1.83 to convert to µmol/mol heme.



APPENDIX 32

Reference Ranges for Serum Transferrin Receptor in Children and Adolescents *
























Age Groups 2.5% Reference Limit mg/L 97.5% Reference Limit mg/L
6 months to 4 years 1.5 (1.4-1.5) 3.3 (3.1-3.4)
4 to 10 years 1.3 (1.3-1.4) 3.0 (2.9-3.2)
10 to 16 years 1.2 (1.1-1.2) 2.7 (2.7-2.8)
>16 years 0.9 (0.9-1.0) 2.3 (2.2-2.4)

From Suominen, P, Virtanen A, Lehtonen-Veronmaa M, et al: Regression-based reference limits for serum transferrin receptor in children 6 months to 16 years of age. Clin Chem 47:935–937, 2001.

* The 95% confidence interval for each limit is given in parentheses.



APPENDIX 33

Percentile Distributions for Plasma Folate, RBC folate, Vitamins B 6 and B 12 , Holotranscobalamin, and Total Homocysteine of Healthy European Adolescents 12.5 to 17.49 Years of Age

























































































































PF(nmol/L) RBC Folate
nmol/L
PLP (nmol/L) Cbl (pmol/L) Holo-TC
(pmol/L)
tHcy (µmol/L)
N 1049 1040 974 1051 1017 1050
Mean 18.7 784.2 63.2 349.4 63.4 7.4
SD 10.5 340.9 51.9 143.5 33.7 3.8
Percentile 2.5 6.4 315.5 16.6 154.4 27.4 3.7
5 7.6 378.8 20.0 170.8 30.9 3.9
10 9.1 428.9 25.0 193.0 35.2 4.4
25 11.8 553.0 34.7 240.0 44.4 5.4
50 16.0 721.9 49.1 319.0 57.8 6.7
75 22.1 942.3 75.7 434.9 73.0 8.4
90 31.7 1214.0 113.9 557.0 91.7 10.5
95 39.0 1389.3 149.7 638.0 107.1 12.3
97.5 46.4 1582.6 187.3 696.0 127.1 15.7

Cbl, Cobalamin; Holo-TC, holotranscobalamin; PF, plasma folate; PLP, pyridoxal 5-phosphate; RBC, red blood cell; SD, standard deviation.





Smoothed (LMS method) centile curves ( from the bottom to the top : P5, P25, P50, P75, P95) of plasma folate (nmol/L), red blood cell folate (nmol/L), vitamin B 6 (pmol/L), vitamin B 12 (pmol/L), holo-transcobalamin (pmol/L), and total homocysteine (µmol/L) concentrations in males and females. Cbl, Cobalamin; Holo-TC , holo-transcobalamin; PF, plasma folate; PLP , pyridoxal phosphate or Vitamin B 6 ; RBC folate , red blood cell folate; tHcy , total homocysteine.

(From Gonzalez-Gross M, Benser J, Breidenassel C, et al: Gender and age influence blood folate, vitamin B12, vitamin B6, and homocysteine levels in European adolescents: the Helena Study. Nutr Res 32:817–826, 2012.)


APPENDIX 34

Plasma Levels of Vitamin E (α-Tocopherol) in Children and Adolescents










































Age MALES AND FEMALES
µmol/L µg/mL
Premature * 1-8 0.5-3.5
Full Term 2-8 0.5-3.5
2-5 m * 5-14 2.0-6.0
6-24 m * 8-19 3.5-80
2-12 y * 13-21 5.5-9.0
1-6 y 7-21 3.0-9.0
7-12 y 10-21 4.0-9.0
13-19 y 13-24 6.0-10.1

* Meites S, editor: Pediatric clinical chamistry, 3rd ed. Washington, DC, 1989, AACC Press, p. 295–296.


Lockitch G, Halstead AC, Wadsworth L, et al: Age- and sex-specific pediatric reference intervals for zinc, copper, selenium, iron, vitamins A and E and related proteins. Clin Chem 34:1625, 1988. Study based on healthy children; values represent the 0.025th and 0.975th fractiles.



APPENDIX 35

Serum Erythropoietin Levels During the First Year of Life *







































Days After Birth Erythropoietin (mU/mL) Hemoglobin (g/dL) RBC (×10 6 /µL)
0-6 33.0 ± 31.4 (11) 15.6 ± 2.2 (11) 4.51 ± 0.74 (11)
7-50 11.7 ± 3.6 (7) 12.8 ± 1.1 (5) 3.92 ± 0.35 (5)
51-100 21.1 ± 5.5 (13) 11.4 ± 1.0 (10) 4.09 ± 0.51 (10)
101-150 15.1 ± 3.9 (5) 11.2 ± 1.1 (3) 4.21 ± 0.31 (3)
151-200 17.8 ± 6.3 (6)
>201 23.1 ± 9.7 (10) 11.8 ± 0.8 (9) 4.57 ± 0.25 (9)

RBC, Red blood cell.

From Yamashita H, Kukita J, Ohga S: Serum erythropoietin levels in term and preterm infants during the first year of life. Am J Pediatr Hematol Oncol 16:213, 1994.

* Values are expressed as mean ± standard deviation; number of specimens is within parentheses.



APPENDIX 36

Plasma Erythropoietin Reference Ranges in Children and Adolescents *

















































Age (y) MALE SUBJECTS FEMALE SUBJECTS
2.5% 97.5% 2.5% 97.5%)
1-3 1.7 17.9 2.1 15.9
4-6 3.5 21.9 2.9 8.5
7-9 1.0 13.5 2.1 8.2
10-12 1.0 14.0 1.1 9.1
13-15 2.2 14.4 3.8 20.5
16-18 1.5 15.2 2.0 14.2

y, Years.

From Krafte-Jacobs B, Williams J,. Soldin SJ, Plasma erythropoietin reference ranges in children. J Pediatr 126:601, 1995.

* Data obtained from a total of 1122 hospitalized and outpatient children ages 1 to 18 years. Levels found in anemic patients cannot be compared with normal values. In fact, as long as the erythropoietin-generating apparatus in the kidney is efficient, serum levels increase exponentially as the hematocrit concentration decreases. Serum erythropoietin must therefore be evaluated in relation to the degree of anemia, and every single laboratory should determine the exponential regression of serum erythropoietin versus hematocrit (or hemoglobin) in a home-made reference population of anemic subjects and define the 95% confidence limits. The patients gathered to calculate a reference regression equation should have an anemia with a single simple mechanism and no evidence of either renal failure or excessive cytokine production (i.e., normal values for C-reactive protein and α 2 -globulins). Patients with chronic iron-deficiency anemia caused by nonneoplastic and noninflammatory chronic blood loss have the advantages of being easily found, unequivocably defined, and homogeneous. They could become the universal reference population, although patients with hemolytic anemia or thalassemia intermedia also may be studied as reference subjects. Serum erythropoietin levels are also much higher for hemoglobin concentration in hypoplastic than in hyperplastic states. Thus for the same hemoglobin concentration, serum erythropoietin levels are lower in thalassemia intermedia than in Diamond-Blackfan anemia.

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Apr 1, 2019 | Posted by in HEMATOLOGY | Comments Off on Appendices Reference Values in Infancy and Childhood
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