Sains Malaysiana 44(12)(2015): 1653–1659

Improvement in the Diagnostics of Iron Deficiency Anemia

using Multiple Marker Combinations

(Penambahbaikan dalam Diagnostik Anemia Kekurangan Zat Besi

menggunakan Gabungan Penanda Berganda)

EUN-SUK YANG*¹, YU-SEOP KIM^2,3, CHAN-YOUNG PARK^2,3, JONG-DAE KIM^2,3& HYE-JEONG SONG^2,3

¹Department of Computer Engineering, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Korea

²Department of Ubiquitous Computing, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Korea

³Bio-IT Research Center, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702

Korea

Diserahkan: 1 September 2014/Diterima: 23 Jun 2015

ABSTRACT

Anemia of chronic disease (ACD) frequently occurred in patients with chronic inflammatory diseases and can be treated by treating the underlying disease. On the other hand, iron-deficiency anemia (IDA), the most common type of anemia, occurred with iron loss or when the iron requirement of the body was increased. Since the treatment methods for ACD and IDA differ, it is important to clinically distinguish between the two types of anemia. In this study, we investigated and evaluated the performance of a number of biomarkers, including ferritin, soluble transferrin receptor (sTfR), hepcidin, C-reactive protein (CRP) and combination markers containing ferritin for the diagnosis of IDA using serum samples from Korean patients (80 ACD and 48 IDA Korean patients). Among the single markers, ferritin exhibited the best performance with 98.58% AUC and 97.50% sensitivity. In this study, a combination of two biomarkers was used to differentially diagnose IDA and ACD. Among the combination markers, ferritin + sTfR showed the best performance with 99.51% AUC and 98.75% sensitivity. We found that the ferritin + sTfR combination showed the best diagnostic performance with 1.25% higher SN than ferritin alone. Moreover, it also showed 10% better diagnostic performance than the single ferritin marker within the data range where the distinction between ACD and IDA is unclear. We propose that using combination markers containing ferritin may diagnose IDA more accurately and facilitate the determination of the appropriate anemia treatment to expedite patient recovery.

Keywords: Index; iron deficiency anemia; multianalyte; transferin serum

ABSTRAK

Anemia penyakit kronik (ACD) kerap berlaku kepada pesakit dengan penyakit radang kronik dan boleh dirawat dengan merawat penyakit yang mendasarinya. Sebaliknya, anemia kekurangan zat besi (IDA) adalah jenis anemia yang paling biasa berlaku dengan kehilangan zat besi atau apabila keperluan zat besi dalam badan bertambah. Oleh kerana kaedah rawatan untuk ACD dan IDA berbeza, adalah penting secara klinikal untuk membezakan antara kedua-dua jenis anemia. Dalam kajian ini, kami mengkaji dan menilai prestasi beberapa penanda biologi, termasuk feritin, transferin larut reseptor (sTfR), hepcidin, protein C-reaktif (CRP) dan penanda gabungan yang mengandungi feritin untuk diagnosis IDA menggunakan sampel serum daripada pesakit warga Korea (80 ACD dan 48 IDA pesakit warga Korea). Antara penanda tunggal, feritin menunjukkan prestasi yang terbaik dengan 98.58% AUC dan 97.50% kepekaan. Dalam kajian ini, gabungan dua penanda biologi telah digunakan untuk mendiagnosis IDA dan ACD secara berbeza. Antara penanda kombinasi, feritin + sTfR menunjukkan prestasi yang terbaik dengan 99.51% AUC dan 98.75% kepekaan. Kami mendapati bahawa gabungan feritin + sTfR menunjukkan prestasi diagnostik yang terbaik dengan 1.25% SN lebih tinggi daripada feritin sahaja. Selain itu, ia juga menunjukkan prestasi diagnostik 10% lebih baik daripada penanda feritin tunggal dalam julat data dengan perbezaan antara ACD dan IDA adalah tidak jelas. Kami mencadangkan bahawa penggunaan penanda gabungan yang mengandungi feritin boleh mendiagnosis IDA dengan lebih tepat dan memudahkan penentuan rawatan anemia yang sesuai untuk mempercepatkan pemulihan pesakit.

Kata kunci: Anemia kekurangan zat besi; indeks; pelbagai analit; serum transferin

RUJUKAN

MedicineNet.com. http://www.medicinenet.com.

Calvey, H.D. & Castleden, C.M. 1987. Gastrointestinal investigations for anaemia in the elderly. Age and Ageing 16(6): 399-404.

Chang, J., Bird, R., Clague, A. & Carter, A. 2007. Clinical utility of serum soluble transferrin receptor levels and comparison with bone marrow iron stores as an index for iron-deficient erythropoiesis in a heterogeneous group of patients. Pathology 39(3): 349-353.

Cheong, K.S., Kim, Y.S., Park, C.Y., Song, H.J. & Kim, J.D. 2013. Development of MATLAB-based data visualization tool for early cancer detection. Advanced Science and Technology Letters 29: 234-236.

Clark, S.F. 2009. Iron deficiency anemia: Diagnosis and management. Current Opinion in Gastroenterology 25(2): 122-128.

Geerts, I., Vermeersch, P. & Joosten, E. 2012. Evaluation of the first commercial hepcidin ELISA for the differential diagnosis of anemia of chronic disease and iron deficiency anemia in hospitalized geriatric patients. International Scholarly Research Notices 2012: 567491.

Goyal, R., Das, R., Bambery, P. & Garewal, G. 2008. Serum transferrin recoptor-ferritin index shows concomitant iron deficiency anemia and anemia of chronic disease is common in patients with rheumatoid arthritis in north India. Indian Journal of Pathology and Microbiology 51(1): 102-104.

Lipschitz, D.A., Cook, J.D. & Finch, C.A. 1974. A clinical evaluation of serum ferritin as an index of iron stores. New England Journal of Medicine 290(22): 1213-1216.

Mclntyre, A.S. & Long, R.G. 1993. Prospective survey of investigations in outpatients referred with iron deficiency anaemia. Gut 34(8): 1102-1107.

Pepe, M.S. & Cai, T. & Longton, G. 2006. Combining predictors for classification using the area under the receiver operating characteristic curve. Biometrics 62(1): 221-229.

Punnonen, K., Irjala, K. & Rajamäki, A. 1997. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 89(3): 1052-1057.

Remacha, A.F., Sarda, M.P., Parellada, M., Ubeda, J. & Manteiga, R. 1998. The role of serum transferrin receptor in the diagnosis of iron deficiency. Haematologica 83(11): 963-966.

Theurl, I., Aigner, E., Theurl, M., Nairz, M., Seifert, M., Schroll, A., Sonnweber, T., Eberwein, L., Witcher, D.R., Murphy, A.T., Wroblewski, V.J., Wurz, E., Datz, C. & Weiss, G. 2009. Regulation of iron homeostasis in Anemia of chronic disease and iron deficiency anemia: Diagnostic and therapeutic implications. Blood 113(21): 5277-5286.

Weiss, G. & Goodnough, L.T. 2005. Anemia of chronic disease. New England Journal of Medicine 352(10): 1011-1023.

*Pengarang untuk surat-menyurat; email: miriam219@hallym.ac.kr