Investigation of ischemia modified albumin levels in patients with lower limb ischemia

Abstract

Aim: Acute limb ischemia occurs after the embolism or thrombosis and if it is not treated it may result in limb loss and even death. In addition, late diagnosis eliminates the chance of immediate intervention. Therefore, early diagnosis is crucial. It has been reported that ischemic modified albumin levels are known to be increased in acute ischemic conditions such as myocardial, cerebral and pulmonary infarctions. The aims of this study were to determine the levels of ischemic modified albumin in lower limb ischemia and to investigate its usability as an auxiliary parameter for early diagnosis. Materials and Methods: 24 patients (5 females, 19 males) with lower limb ischemia (patient group: 23-89 years old), 34 healthy individuals composed of 19 females and 15 males (control group; 20-75 years old) who were totally 58 cases were included in the study. The ischemic modified albumin levels in the serum samples obtained from individuals in the patient and control groups who met the inclusion criteria, were analyzed with the ELISA kit (Organo Teknika, Austria) in line with the manufacturer's instructions. Mann Whitney U test was used to compare ischemic modified albumin levels between groups. Results: It was found that patients with limb ischemia had a significantly increased ischemic modified albumin level compared to the control group (p <0.001). It was detected that the sensitivity value was 91.7 and the specificity value was 82.4 in the ROC curve analysis. Conclusion: We think that the significant increase in serum ischemic modified albumin levels in lower limb ischemia may be useful in the diagnosis of limb ischemia.

Keywords

• Ischemia
• limb ischemia
• ischemia modified albumin
• early diagnosis

Alt ekstremite iskemisi olan hastalarda iskemi modifiye albümin düzeylerinin araştırılması

Abstract

Amaç: Akut ekstremite iskemisi, emboli ya da tromboz akabinde ortaya çıkmakta ve tedavi edilmezse ekstremite kaybı ve hatta ölümle sonuçlanabilmektedir. Ayrıca, tanının gecikmesi acil girişim şansını ortadan kaldırmaktadır. Bu nedenle, erken tanı büyük önem taşımaktadır. Miyokard enfarktüsü, serebral infarkt ve pulmoner infarkt gibi akut iskemik durumlarda düzeylerinin yükseldiği bildirilen iskemi modifiye albüminin, iskemik durumlarda tanı belirteci olabileceği bildirilmektedir. Bu çalışmanın amacı da alt ekstremite iskemisinde iskemi modifiye albüm düzeyini belirlemek ve erken tanıya yardımcı bir parametre olarak kullanılabilirliğini araştırmaktır. Yöntem: Bu çalışmaya alt ekstremite iskemisi olan 5’i kadın, 19’u erkekten oluşan 24 hasta (hasta grubu; 23-89 yaş) ve kontrol amaçlı gelen 19’u kadın, 15’i erkekten oluşan 34 sağlıklı gönüllü (kontrol gurubu; 20-75 yaş) olmak üzere 58 kişi dahil edildi. Dahil edilme kriterlerine uygun hasta ve kontrol gruplarındaki bireylerden elde edilen serum örneklerindeki iskemi modifiye albüm düzeyleri, ELİSA kiti (Organo Teknika, Avusturya) ile analiz edildi. Gruplar arası iskemi modifiye albüm düzeylerinin karşılaştırılmasında Mann Whitney U testi kullanıldı. Bulgular: Akut ekstremite iskemisi olan hastalarda, kontrol grubundakiler ile karşılaştırıldığında önemli ölçüde artmış iskemi modifiye albüm düzeyi olduğu tespit edildi (p <0.001). ROC eğrisi analizinde sensitivite değeri 91.7 ve spesifite değeri 82.4 olarak tespit edildi. Sonuç: Alt ekstremite iskemisinde serum iskemi modifiye albüm düzeylerinde görülen önemli artışın, ekstremite iskemisinin tanısında yararlı olabileceğini düşünmekteyiz.

Keywords

• İskemi
• Ekstremite iskemisi
• İskemi modifiye albumin
• Erken tanı

References

1. 1. Lippi G, Montagnan M, Guidi GC. Albumin cobalt binding and ischemia modified albumin generation: an endogenous response to ischemia? International journal of cardiology. 2006; 108:410-411. doi: 10.1016/j.ijcard.2005.03.040
2. 2. Marcus F, Claude EV, Josephine M, et al. An Exceptional Cause of Acute Limb Ischemia: Nicolau Syndrome—Single-Center Experience with 4 Cases. Annals of vascular surgery. 2019; 58: 383.e7-383.e11. doi: 10.1016/j.avsg.2018.11.022
3. 3. Bar–OrD, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia—a preliminary report. The Journal of emergency medicine. 2000; 19:311-315. doi: 10.1016/s0736-4679(00)00255-9
4. 4. Uzel M, Oray NC, Bayram B, et al. Novel biochemical marker for differential diagnosis of seizure: ischemia-modified albumin. The American journal of emergency medicine. 2014; 32(9), 962-965. doi: 10.1016/j.ajem.2014.05.003
5. 5. Bar‐Or D, Curtis G, Rao N, et al. Characterization of the Co2+ and Ni2+ binding amino‐acid residues of the N‐terminus of human albumin: An insight into the mechanism of a new assay for myocardial ischemia. European Journal of Biochemistry. 2001; 268(1), 42-48. doi: 10.1046/j.1432-1327.2001.01846.x
6. 6. Cho D K, Choi J H, Kim S H, et al. Ischemia-modified albumin is a highly sensitive serum marker of transient myocardial ischemia induced by coronary vasospasm. Coronary artery disease. 2007; 18(2), 83-87. doi: 10.1097/MCA.0b013e328010a49f
7. 7. Mentese A, Mentese U, Turedi S, et al. Effect of deep vein thrombosis on ischaemia-modified albumin levels. Emergency Medicine Journal. 2008; 25(12), 811-814. 10.1136/emj.2007.056614
8. 8. Troxler M, Thompson D, Homer-Vanniasinkam S. Ischaemic skeletal muscle increases serum ischaemia modified albumin. European journal of vascular and endovascular surgery. 2006; 31(2), 164-169. doi:10.1016/j.ejvs.2005.06.019

9. 9. Gunduz A, Mentese A, Turedi S, et al. Serum ischaemia-modified albumin increases in critical lower limb ischaemia. Emergency Medicine Journal. 2008; 25(6), 351-353.
10. 10. Sbarouni E, Georgiadou P, Theodorakis GN, et al. Ischemia-modified albumin in relation to exercise stress testing. Journal of the American College of Cardiology. 2006; 48(12), 2482-2484. doi: 10.1016/j.jacc.2006.06.007
11. 11. Keating L, Benger J R, Beetham R, et al. The PRIMA study: presentation ischaemia-modified albumin in the emergency department. Emergency Medicine Journal. 2006; 23(10), 764-768. doi: 10.1136/emj.2006.036269
12. 12. Refaai MA, Wright RW, Parvin CA, et al. Ischemia-modified albumin increases after skeletal muscle ischemia during arthroscopic knee surgery. Clinica Chimica Acta. 2006; 366(1-2), 264-268. doi: 10.1016/j.cca.2005.10.020
13. 13. Turedi S, Gunduz A, Mentese A, et al. Value of ischemia-modified albumin in the diagnosis of pulmonary embolism. The American journal of emergency medicine. 2007; 25(7), 770-773.
14. 14. Abboud H, Labreuche J, Meseguer E, et al. Ischemia-modified albumin in acute stroke. Cerebrovascular Diseases. 2007; 23(2-3), 216-220. doi: 10.1159/000097644
15. 15. Coverdale JP, Katundu KG, Sobczak AI, et al. Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2018; 135, 147-157. doi: 10.1016/j.plefa.2018.07.014
16. 16. Yosunkaya Ş, Can U. İskemide Yeni Bir Marker: İskemi Modifiye Albumin. Koşuyolu Kalp Dergisi. 2017; 20(2), 148-152.
17. 17. Yang G, Zhou Y, He H, et al. Ischemia-modified albumin, a novel predictive marker of in-hospital mortality in acute aortic dissection patients. Frontiers in physiology. 2019; 10, 1253. https://doi.org/10.3389/fphys.2019.01253.
18. 18. Maneewong K, Mekrungruangwong T, Luangaram S, et al. Combinatorial determination of ischemia modified albumin and protein carbonyl in the diagnosis of nonST-elevation myocardial infarction. Indian Journal of Clinical Biochemistry. 2011; 26(4), 389-395. doi: 10.1007/s12291-011-0118-2
19. 19. Dursun A, Okumus N, Zenciroglu A. Ischemia-modified albumin (IMA): could it be useful to predict perinatal asphyxia?. The Journal of Maternal-Fetal & Neonatal Medicine. 2012; 25(11), 2401-2405. doi: 10.3109/14767058.2012.697943
20. 20. Hogg K, Hinchliffe E, Halsam S, et al. Is ischaemia-modified albumin a test for venous thromboembolism?. Emergency Medicine Journal. 2012; 29(6), 455-459. doi:10.4236/ojrd.2014.41004.
21. 21. Gunduz A, Turedi S, Mentese A, et al. Ischemia-modified albumin in the diagnosis of acute mesenteric ischemia: a preliminary study. The American journal of emergency medicine. 2008; 26(2), 202-205. doi: 10.1016/j.ajem.2007.04.030
22. 22. Mitsudo S, Brandt LJ. Pathology of intestinal ischemia. The Surgical clinics of North America. 1992; 72(1), 43-63. 10.1016/S0039-6109(16)45627-6
23. 23. Apple FS, Quist HE, Otto AP, et al. Release characteristics of cardiac biomarkers and ischemia-modified albumin as measured by the albumin cobalt-binding test after a marathon race. Clinical Chemistry. 2002; 48(7), 1097-1100.
24. 24. Apple FS, Wu AH, Mair J, et al. Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome. Clinical chemistry. 2005; 51(5), 810-824. doi: 10.1373/clinchem.2004.046292
25. 25. Erdem SS, Yerlikaya FH, Çiçekler H ve ark. Association between ischemia-modified albumin, homocysteine, vitamin B12 and folic acid in patients with severe sepsis. Clinical Chemistry and Laboratory Medicine (CCLM). 2012; 50(8), 1417-1421. doi: 10.1515/cclm-2011-0794
26. 26. Fidan E, Mentese A, Kavgaci H ve ark. Increased ischemia-modified albumin levels in patients with gastric cancer. Neoplasma. 2012; 59(4), 393. doi: 10.4149/neo_2012_051
27. 27. Stachowicz‐Stencel T, Synakiewicz A, Owczarzak A, et al. Ischemia‐modified albumin as a biochemical marker in children with neuroblastoma and soft tissue sarcomas. Journal of clinical laboratory analysis. 2011; 25(4), 255-258. doi: 10.1002/jcla.20469
28. 28. Dominguez-Rodriguez A, Abreu-Gonzalez P. Current role of ischemia-modified albumin in routine clinical practice. Biomarkers. 2010; 15(8), 655-662. doi: 10.3109/1354750X.2010.513449
29. 29. Roy D, Quiles J, Aldama G, et al. Ischemia modified albumin for the assessment of patients presenting to the emergency department with acute chest pain but normal or non-diagnostic 12-lead electrocardiograms and negative cardiac troponin T. International journal of cardiology. 2004; 97(2), 297-301. doi:10.1016/j.ijcard.2004.05.042
30. 30. Zapico-Muñiz E, Santaló-Bel M, Mercé-Muntañola J, et al. Ischemia-modified albumin during skeletal muscle ischemia. Clinical Chemistry. 2004; 50(6), 1063-1065. Doi: 10.1373/clinchem.2003.027789