Objective: Juvenile Idiopathic Arthritis (JIA) is commonly associated with different types of anemia. The diagnosis and treatment of IDA is a medical necessity; being a well-recognized cause of both short and long term morbidity plus being strongly related to poor disease outcome. In the presence of concomitant chronic illness or inflammation, the diagnosis of iron deficiency using the conventional laboratory parameters is a major medical challenge. Therefore, the utility of two recent iron status parameters; hepcidin-25 "active form of iron metabolism negative regulator" and reticulocyte hemoglobin content (CHr) "functional anemia indicator" was compared to that of two conventional ones; transferrin saturation (TSAT) and red cell distribution width percentages (RDW%) in diagnosing iron deficiency anemia in patients with JIA.

Methods: Blood samples were obtained from 43 JIA patients whose ages ranged from 3 to 16 years and 20 age and sex matched healthy children as control group. Three different types of anemia; iron deficiency anemia (IDA), anemia of chronic disease (ACD) and combined anemia (IDA/ACD) were identified within the studied patients using iron profile, ESR and C-reactive protein. Serum hepcidin-25 was assessed by ELISA technique; CHr, TSAT% and RDW% were all estimated using Siemens ADVIA 2120 analyzer in patients and the control group.

Results: Anemia was identified in 22 (51.2%) patients. Serum hepcidin-25 and TSAT% were significantly lower in IDA than ACD & IDA/ACD patients (p= 0.032 and p=0.034 for hepcidin and p= 0.004 and p=0.012 for TSAT%). Significantly lower CHr and higher RDW% were found in IDA/ACD compared to ACD patients (p= 0.032 and p< 0.001, respectively). Serum hepcidin ≤ 3.8ng/mL and TSAT% ≤ 5.8% differentiated IDA from both ACD and IDA/ACD with 80 and 100% sensitivity and 88.24% specificity. CHr ≤24.4pg and RDW % > 16.4% showed 80 and 90% sensitivity and 100% specificity; distinguishing IDA/ACD from ACD.

Conclusion: Serum hepcidin and CHr were not superior to TSAT% and RDW%; discriminating among different types of anemia in JIA patients.

Table 1.

Comparison between anemia subgroups according to CHr and serum hepcidin

IDA
(n=5)		ACD
(n=6)		Combined anemia
(n=7)		Control
(n=20)		p
CHr (pg) 23.61 ± 3.80a 27.36 ± 2.30b 23.37 ± 3.18a 30.54 ± 1.99 <0.001* 
Serum hepcidin (ng/ml) 3.60 (3.0-4.9)bc 5.10 (3.10 - 90.0) 7.15 (3.1-60.0) 5.0 (0.10-10.8) 0.121 
IDA
(n=5)		ACD
(n=6)		Combined anemia
(n=7)		Control
(n=20)		p
CHr (pg) 23.61 ± 3.80a 27.36 ± 2.30b 23.37 ± 3.18a 30.54 ± 1.99 <0.001* 
Serum hepcidin (ng/ml) 3.60 (3.0-4.9)bc 5.10 (3.10 - 90.0) 7.15 (3.1-60.0) 5.0 (0.10-10.8) 0.121 

Data was expressed as Mean ± SD. for normally distributed data and Median (Min. - Max.) for abnormaly distrbutied data

a: Significant with control gorup

b: Significant with combined anemia group

c: Significant with ACD group

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Table 2.

Comparison among anemia subgroups and control group according to RDW & TSAT%

IDA
(n=5) 		ACD
(n=7) 		Combined anemia
(n=10) 		Control
(n=20) 		Test of sig. p
RDW%       
Min. - Max. 17.30 - 19.90 13.10 - 16.40 15.60 - 22.0 12.40 - 15.80 F=45.032* <0.001* 
Mean ± SD. 18.42 ± 1.04 14.49 ± 1.30 18.46 ± 1.92 13.47 ± 0.86 
Median 2.62 13.90 18.20 13.10 
Sch p* p1<0.001* ,p2=0.362,p3<0.001* ,p4=1.000,p5<0.001* ,p6<0.001*   
TSAT %       
Min. - Max. 4.20 - 5.80 6.0 - 20.50 4.40 - 26.0 11.0 - 40.0 KW χ2 =* <0.001* 
Mean ± SD. 4.78 ± 0.64 10.73 ±4.82 13.82 ± 8.63 22.71 ± 8.32 
Median 4.50 10.0 12.80 20.70 
MW p1 0.001* 0.001* 0.016*    
MW p2 0.012* 0.660     
MW p3 0.004*     
IDA
(n=5) 		ACD
(n=7) 		Combined anemia
(n=10) 		Control
(n=20) 		Test of sig. p
RDW%       
Min. - Max. 17.30 - 19.90 13.10 - 16.40 15.60 - 22.0 12.40 - 15.80 F=45.032* <0.001* 
Mean ± SD. 18.42 ± 1.04 14.49 ± 1.30 18.46 ± 1.92 13.47 ± 0.86 
Median 2.62 13.90 18.20 13.10 
Sch p* p1<0.001* ,p2=0.362,p3<0.001* ,p4=1.000,p5<0.001* ,p6<0.001*   
TSAT %       
Min. - Max. 4.20 - 5.80 6.0 - 20.50 4.40 - 26.0 11.0 - 40.0 KW χ2 =* <0.001* 
Mean ± SD. 4.78 ± 0.64 10.73 ±4.82 13.82 ± 8.63 22.71 ± 8.32 
Median 4.50 10.0 12.80 20.70 
MW p1 0.001* 0.001* 0.016*    
MW p2 0.012* 0.660     
MW p3 0.004*     

KW c2 : Chi square for Kruskal Wallis test F: F test (ANOVA)

p1: p value for comparing between control and IDA

p2: p value for comparing between control and ACD

p3: p value for comparing between control and combined anemia

p4: p value for comparing between combined anemia and IDA

p5: p value for comparing between combined anemia and ACD

p6: p value for comparing between ACD group and IDA group

MW: Mann Whitney test Sch: Post Hoc Test (Scheffe)

*: Statistically significant at p ≤ 0.05

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Table 3.

Agreement (sensitivity, specificity and accuracy) for serum hepcidin and TSAT% with IDA vs. ACD and combined anemia in JIA patients

ACD and combined anemiaIDASensitivitySpecificityPPVNPVAccuracy
Serum hepcidin (ng/ml) >3.8 15 1 80.0 88.24 66.67 93.75 86.36 
<3.8 2 4 
TSAT% >5.8 15 0 100.0 88.24 71.43 100.0 90.91 
≤5.8 2 5 
ACD and combined anemiaIDASensitivitySpecificityPPVNPVAccuracy
Serum hepcidin (ng/ml) >3.8 15 1 80.0 88.24 66.67 93.75 86.36 
<3.8 2 4 
TSAT% >5.8 15 0 100.0 88.24 71.43 100.0 90.91 
≤5.8 2 5 
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Table 4.

Agreement (sensitivity, specificity and accuracy) for CHr and RDW% with ACD vs. combined anemia in JIA patients

ACDCombined anemiaSensitivitySpecificityPPVNPVAccuracy
CHr >24.4 7 2 80 100.0 100.0 77.78 88.24 
≤24.4 0 8 
RDW % ≤16.4 7 1 90.0 100.0 100.0 87.50 94.12 
>16.4 0 9 
ACDCombined anemiaSensitivitySpecificityPPVNPVAccuracy
CHr >24.4 7 2 80 100.0 100.0 77.78 88.24 
≤24.4 0 8 
RDW % ≤16.4 7 1 90.0 100.0 100.0 87.50 94.12 
>16.4 0 9 
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Disclosures

No relevant conflicts of interest to declare.

Topics:
anemia, arthritis, juvenile rheumatoid, iron, hepcidin, iron deficiency anemia, anemia of chronic disorder, chronic disease, c-reactive protein, inflammation, iron deficiency

Author notes

*

Asterisk with author names denotes non-ASH members.

This icon denotes a clinically relevant abstract

© 2015 by The American Society of Hematology
2015
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