Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc
Journal website https://www.thejh.org

Original Article

Volume 11, Number 3, June 2022, pages 92-108


Hematological, Biochemical Properties, and Clinical Correlates of Hemoglobin S Variant Disorder: A New Insight Into Sickle Cell Trait

Figures

Figure 1.
Figure 1. Comparison of characteristics of anemia between SCT subjects and SCD patients. Bar graphs show the percentages of Hb values (g/dL) (a), RDW value (b), the RBC count (× 106/L) (c), RBC volume (MCV, fL) (d) and chromicity (MCHC, g/dL) (e). SCT: sickle cell trait; SCD: sickle cell disease; Hb: hemoglobin; RDW: red cell distribution width; RBC: red blood cell; MCV: mean corpuscular volume; MCHC: mean corpuscular hemoglobin concentration.
Figure 2.
Figure 2. Receiver operating characteristic curves for discriminating cases with Hb S variant (group 1) from healthy controls by: (a) RDW, RDWI and Mentzer index, (b) GK, EF and SLI, (c) SI, RI and EI, and (d) Sir I and HH. Hb: hemoglobin; RDW: red cell distribution width; RDWI: red cell distribution width index; GK: Green and King index; EF: England and Frazer index; SL: Shine and Lal index; SI: Srivastava index; RI: Ricerca index; EI: Ehsani index; Sir I: Sirdah index; HH: Huber-Herklotz index.
Figure 3.
Figure 3. Receiver operating characteristic curves for discriminating patients with SCD from subjects with SCT by: (a) Hb, MCHC and Hct, (b) Hb A, Hb A2, Hb F and Hb S, (c) RDW, RDWI and Mentzer index, (d) GK, EF and SL, (e) SI, RI and EI, and (f) Sir I and HH. SCT: sickle cell trait; SCD: sickle cell disease; Hb: hemoglobin; MCHC: mean corpuscular hemoglobin concentration; Hct: hematocrit; RDW: red cell distribution width; RDWI: red cell distribution width index; GK: Green and King index; EF: England and Frazer index; SL: Shine and Lal index; SI: Srivastava index; RI: Ricerca index; EI: Ehsani index; Sir I: Sirdah index; HH: Huber-Herklotz index.
Figure 4.
Figure 4. I: Schematic box plots representing the correlations of RDW, RDWI, MI and GKI results with hematological parameters among hemoglobin S variant cases. First, correlation between RDW and (a) Hb levels, (b) Hb F, (c) Hb S, (d) reticulocyte count; second, correlation between RDWI and (e) Hb levels, (f) Hb F, (g) Hb S, (h) reticulocyte count; third, correlation between Mentzer index and (i) Hb levels, (j) Hb F, (k) Hb S, (l) reticulocyte count; fourth, correlation between GK and (m) Hb levels, (n) Hb F, (o) Hb S, (p) reticulocyte count. II: Schematic box plots representing the correlations of (a-d) EF, (e-h) SL, (i-l) SI and (m-p) RI results with hematological parameters among hemoglobin S variant cases. Correlated as indicated in the figure. III: Schematic box plots representing the correlations of (a-d) EI, (e-h) Sir I and (i-l) HH results with hematological parameters among hemoglobin S variant cases. Correlated as indicated in the figure. IV: Schematic box plots representing correlations of some hematological parameters (a-f) among hemoglobin S variant cases. RDW: red blood cell distribution width; RDWI: red blood cell distribution width index; MI: Mentzer index; GKI: Green and King index; EF: England and Frazer index; SL: Shine and Lal index; SI: Srivastava index; RI: Ricerca index; EI: Ehsani index; Sir I: Sirdah index; HH: Huber-Herklotz index. r: Spearman rank correlation coefficient; P: P value.
Figure 5.
Figure 5. Radiological findings of SCD and SCT cases of the study. SCT: sickle cell trait; SCD: sickle cell disease.
Figure 6.
Figure 6. Diagnostic algorithm for identification of SCD and SCT. SCT: sickle cell trait; SCD: sickle cell disease; HHA: hereditary hemolytic anemia; CBC: complete blood cell count; PBS: peripheral blood smear; AIHA: autoimmune hemolytic anemia; MAHA: microangiopathic hemolytic anemia; TTP: thrombotic thrombocytopenic purpura; HUS: hemolytic uremic syndrome; PNH: paroxysmal nocturnal hemoglobinuria.

Tables

Table 1. Demographic, Clinical and Hematological Characteristics of Studied Groups
 
Variable, n (%)Hb S variant (group 1) (n = 55)Controls (group 2) (n = 60)P- valueSCD (group 1a) (n = 24)SCT (group 1b) (n = 31)P-value
P value was calculated with unpaired sample t-test. *P value was calculated with the Mann-Whitney test. #P value was calculated with the χ2 test. P value < 0.05 was considered significant. SCD: sickle cell disease; SCT: sickle cell trait; SD: standard deviation; CBC: complete blood cell count; WBC: white blood cell; RBC: red blood cell; Hb: hemoglobin; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; Hct: hematocrit; MI: Mentzer index; RDW: red cell distribution width; RDWI: red cell distribution width index; GK: Green and King index; EF: England and Fraser index; SL: Shine and Lal index; SI: Srivastava index; RI: Ricerca index; EI: Ehsani index; Sir I: Sirdah index; HH: Huber-Herklotz index.
Age (years)0.7960.041
  Mean ± SD26.35 ± 9. 8525.93 ± 11.7725.96 ± 10.3130.71 ± 9.73
  Median26272229
  Range18 - 5218 - 4518 - 4818 - 52
Gender0.193#
  Male31 (56.4)26 (43.3)14 (58.3)17 (54.8)0.421
  Female24 (43.6)34 (56.7)10 (41.7)14 (45.2)
Residence0.074#0.863#
  Assiut18 (32.7)21 (35)9 (37.5)9 (41.9)
  El Minia1 (1.8)4 (6.7)1 (4.2)0 (0.0)
  Sohag12 (21.8)27 (45)6 (25)6 (35.5)
  Qena8 (14.5)5 (8.3)1 (4.2)7 (0.0)
  Luxor2 (3.6)0 (0.0)1 (4.2)1 (3.2)
  Aswan3 (5.5)1 (1.7)1 (4.1)2 (3.2)
  Red Sea5 (9.1)2 (3.3)2 (8.3)3 (6.5)
  New Valley6 (10.9)0 (0.0)3 (12.5)3 (3.2)
Clinical presentation0.000#
  Acute hemolysis11 (20)9 (37.5)2 (6.4)
  Painful crisis9 (16.3)8 (33.3)1 (3.2)
  Acute abdomen4 (7.3)4 (16.3)0 (0)
  Anemic manifestations19 (34.5)6 (25)1 (3.2)
  Jaundice4 (7.2)3 (12.5)1 (3.2)
  Acute chest syndrome2 (3.6)2 (8.3)0 (0)
  Obstructive jaundice7 (12.7)6 (25)1 (3.2)
  Accidental discovery15 (27.2)0 (0.0)25 (80.6)
  Nephropathy3 (5.4)2 (8.3)1 (3.2)
  Aplastic crisis2 (3.6)2 (8.3)0 (0)
CBC
  WBCs (× 103/L)7.72 ± 4.347.33 ± 1.750.1638.83 ± 5.306.86 ± 3.250.502
  RBCs (× 106/L)5.01 ± 4.935.92 ± 0.53< 0.0013.78 ± 1.315.96 ± 6.340.050
  Hb (g/dL)10.65 ± 3.3114.22 ± 1.54< 0.0019.10 ± 2.2011.85 ± 3.55< 0.001
  MCV (fL)74.67 ± 17.7985.72 ± 4.32< 0.00176.48 ± 9.8673.27 ± 22.140.830
  MCH (pg)25.10 ± 5.4328.27 ± 1.20< 0.00126.31 ± 4.5924.17 ± 5.910.391
  MCHC (g/dL)36.21 ± 10.6132.59 ± 1.260.51831.29 ± 2.1440.02 ± 12.84< 0.001
  Hct (%)35.42 ± 11.7743.82 ± 3.03< 0.00127.23 ± 3.8441.76 ± 11.96< 0.001
  Reticulocytes (%)3.74 ± 2.540.9 ± 0.37< 0.0014.72 ± 3.122.97 ± 1.670.045
  Platelets (× 103/L)300.67 ± 93.84316.73 ± 60.110.149316.13 ± 82.53300.67 ± 93.840.247
Targeted indices
  MI20.56 ± 11.1416.37 ± 2.030.04623.37 ± 10.9118.09 ± 3.110.086
  RDW (%)17.01 ± 3.8613.26 ± 0.80< 0.00117.01 ± 3.8616.19 ± 4.220.030
  RDWI353.43 ± 24.80216.71 ± 26.56< 0.001424.99 ± 201.77298.03 ± 229.090.040
  GK108.37 ± 63.0969.19 ± 8.720.260127 ± 55.9193.20 ± 6.490.009
  EF15.5 ± 22.305.94 ± 8.260.07623.79 ± 11.99.13 ± 22.670.008
  SL1,569.90 ± 656.782,089.21 ± 280.90< 0.0011,608.6 ± 638.101,539.8 ± 679.800.773
  SI6.90 ± 3.545.39 ± 0.600.0238.03 ± 3.946.01 ± 2.960.017
  RI4.81 ± 2.552.52 ± 0.28< 0.0015.43 ± 2.254.32 ± 2.680.018
  EI36.06 ± 19.9032.77 ± 7.340.79938.60 ± 20.4634.09 ± 19.560.164
  Sir I40.59 ± 17.1137.78 ± 5.871.00045.39 ± 15.4536.88 ± 17.640.018
  HH28.90 ± 9.2920.40 ± 1.26< 0.00132.66 ± 8.6426.00 ± 8.850.003

 

Table 2. T-Test Results of Hematological Parameters of SCT Subjects and Control Group
 
Participant groupMeanSDP value
P value was calculated with unpaired sample t-test. SCT: sickle cell trait; SD: standard deviation; WBC: white blood cell; RBCs: red blood cells; Hb: hemoglobin; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; Hct: hematocrit; MI: Mentzer index; RDW: red cell distribution width; RDWI: red cell distribution width index; GK: Green and King index; EF: England and Fraser index; SL: Shine and Lal index; SI: Srivastava index; RI: Ricerca index; EI: Ehsani index; Sir I: Sirdah index; HH: Huber-Herklotz index.
WBCs (× 103/L)Controls7.3291.74760.138
SCT7.0482.9781
RBCs (× 106/L)Controls5.2960.5288< 0.001
SCT4.3681.2013
Hb (g/dL)Controls14.2181.54490.007
SCT12.1743.0627
MCV (fL)Controls85.7324.3223< 0.001
SCT77.77411.6808
MCH (pg)Controls28.2731.2038< 0.001
SCT24.1685.9053
MCHC (g/dL)Controls32.5921.26070.008
SCT40.02312.8395
Platelets (× 103/L)Controls316.7360.1060.027
SCT288.71101.439
Hct (%)Controls43.823.0370.805
SCT40.449.655
Reticulocytes (%)Controls0.8730.3654< 0.001
SCT2.9741.6733
Mentzer indexControls16.36682.027900.779
SCT20.317210.53331
RDW indexControls216.7126.559090.49
SCT345.52246.46697
RDWControls13.26500.803980.002
SCT16.19034.22164
GKControls69.19878.718720.514
SCT93.203164.98447
EFControls5.94408.260770.233
SCT9.134822.67161
SLControls2,089.21280.97225< 0.001
SCT1,539.93679.80101
SIControls5.39220.601890.763
SCT6.01942.96136
RIControls2.52740.27603< 0.001
SCT4.32602.68780
EIControls32.77177.345260.293
SCT34.090319.56032
Sir IControls37.78075.873790.016
SCT36.883217.64508
HHControls20.40381.257610.001
SCT26.00238.85158

 

Table 3. Differences of Hemoglobin Fractions Between SCT Subjects and Control Group
 
HbGroupsMeanStd. deviationStd. error meanP-value
Hb: hemoglobin; SCT: sickle cell trait.
Hb ASCT62.4511.452.05700.000
Controls96.7700.50970.0658
Hb A2SCT3.370.470.95620.009
Controls2.6230.26190.0338
Hb FSCT1.4002.350.42290.014
Controls0.610.510.0650
Hb SSCT34.7810.591.94120.000
Controls0.0000.00000.0000

 

Table 4. Receiver Operating Characteristic Curve Analysis Results and Predictive Values of Evaluated Indices for Differential Diagnosis of SCT Subjects and Control Group
 
VariableAUC (95%)Cut-offSens (%)Spec (%)PPV (%)NPV (%)% Correctly identifiedYIP value
AUC: area under the curve; Sens: sensitivity; Spec: specificity; PPV: positive-predictive value; NPV: negative-predictive value; YI: Youden’s index; SC: sickle cell; SCT: sickle cell trait; RBCs: red blood cell; Hb: hemoglobin; MCHC: mean corpuscular hemoglobin concentration; Hct: hematocrit; RDW: red blood cell distribution width; RDWI: red blood cell distribution width index; GK: Green and King index; EF: England and Frazer index; SL: Shine and Lal index; SI: Srivastava index; RI: Ricerca index; EI: Ehsani index; Sir I: Sirdah index; HH: Huber-Herklotz index.
MCHC0.67 (0.52 - 0.81)SCT > 33.561%81%63%80%75%0.420.009
Retics (%)0.98 (0.96 - 1.02)SCT > 2%70%100%100%87%66%0.70< 0.001
RDW (%)0.70 (0.56 - 0.83)SCT > 14%54%85%65%78%74%0.390.002
RDWI0.63 (0.49 - 0.76)SCT > 240%54%80%59%77%71%0.290.049
SL0.82 (0.70 - 0.93)SCT < 1,78088%71%58%76%82%0.59< 0.001
RI0.79 (0.68 - 0.90)SCT > 2.868%83%68%83%78%0.51< 0.001
Sir I0.35 (0.19 - 0.50)SCT > 3526%52%22%58%43%-0.220.016
HH0.71 (0.58 - 0.84)SCT > 21.555%78%56%77%70%0.330.001