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Thalassemia Syndromes, Haptoglobin, sTfR, HCV
Background :Serum haptoglobin (Hp) is a reliable marker for hemolysis regardless the inflammatory state. Objective: We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV) infection and iron load in ?-thalassemia children. Methods: Twenty two ?-thalassemia major (TM) ,20 ?-thalassemia intermedia (TI) children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered . Serum ferritin , Hp and transferrin receptor levels (sTfR) (by ELISA ) , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (by colorimetric method) were assayed. Markers of hepatitis C virus (HCV) were done by PCR. Results: The mean Hp levels among the studied groups were as follows; 8.02 ± 0.93 (mg/dl) , 8.6 ±0.72 (mg/dl) and 122 ± 18.5(mg/dl) for TM ,TI and the controls respectively . Both patient groups had significantly lower Hp level compared to the controls (P<0.0001) with significant lower level in TM compared to TI children ( P= 0.034) .Significant inverse correlations were found between serum Hp and sTfR levels in thalassemia children combined and in each group (TM and TI) as well as among HCV infected children. STfR was the only significant independent predictor for serum Hp level (t= -5.585 , P<0.0001) . Among HCV infected patients , no significant correlation was found between serum Hp and serum transaminases .Conclusion: Serum Hp depletion in thalassemia had significant relation to disease severity and correlated well with their erythropoietic activity, as assessed by the measurement of sTfR without significant relation HCV infection . Large sample multicenter studies are recommended.
2. Thein SL . Genetic modifiers of ?-thalassemia . Haematologica. 2005 May; 90(5):651-660.
3. Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harb Perspect Med. 2013 Feb 1;3(2):a011775. doi: 10.1101/cshperspect.a011775.
4. El-Beshlawy A, Kaddah N, Moustafa A Mouktar G, Youssry I. Screening for beta-thalassaemia carriers in Egypt: significance of the osmotic fragility test. East Mediterr Health J. 2007 Jul-Aug ;13(4):780-786.
5. Hussein G, Fawzy M, Serafi TE, Ismail EF, Metwally DE, Saber MA, Giansily M, Schved JF, Pissard S, Martinez PA. Rapid detection of beta-Thalassemia alleles in Egypt using naturally or amplified created restriction sites and direct sequencing: a step in disease control. Hemoglobin. 2007;31(1):49-62.
6. Schrier SL. Pathophysiology of thalassemia. Curr Opin Hematol. 2002 Mar ; 9:123-126.
7.Laosombat V. Wongchanchailert M, Sattayasevana B, Wiriyasateinkul A, Fucharoen S. Clinical and hematological features of codon 17,A-T mutation of beta- thalassemia in Thai patients . Eur J Haematol .2001Feb ;66(2):126-129.
8 .Bowman BH, Kurosky A. Haptoglobin: the evolutionary product of duplication, unequal crossing over, and point mutation. Adv Hum Genet. 1982;12:189-261. 453-454.
9. Quaye IK .Haptoglobin, inflammation and disease. Trans R Soc Trop Med Hyg. 2008 Aug;102(8):735-742. doi: 10.1016/j.trstmh.2008.04.010. Epub 2008 May 16.
10. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK. Identification of the haemoglobin scavenger receptor. Nature. 2001 Jan 11;409(6817):198-201.
11. Okazaki T, Yanagisawa Y, Nagai T .Analysis of the affinity of each haptoglobin polymer for hemoglobin by two-dimensional affinity electrophoresis. Clin Chim Acta.1997 Feb ; 258: 137–144.
12. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY. Reference distributions for the positive acute phase serum proteins, alpha1-acid glycoprotein (orosomucoid), alpha1-antitrypsin, and haptoglobin: a practical, simple, and clinically relevant approach in a large cohort. J Clin Lab Anal. 2000; 14: 284–292.
13. Shih AW, McFarlane A, Verhovsek M. Haptoglobin testing in hemolysis: measurement and interpretationAm J Hematol. 2014 April ;89(4):443-447.
14. Körmöczi GF1, Säemann MD, Buchta C Peck-Radosavljevic M, Mayr WR, Schwartz DW, Dunkler D, Spitzauer S, Panzer S.Influence of clinical factors on the haemolysis marker haptoglobin. Eur J Clin Invest. 2006 Mar ;36(3):202-209.
15. Silverman LN, Christenson RH. Protein. In: Burtis CA, Ashwood ER; eds . Tietz Textbook of Clinical Chemistry. Philadelphia, PA: Saunders.1999;494-497.
16. Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E.Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. 2007 May;92(5):583-588.
17. Thomas L. Haptoglobin (Hp)/Hemopexin (Hx). In: Thomas L, editor. Clinical Laboratory Diagnostics. Frankfurt/Main:TH-Books.1998;.663–667.
18. Hillman RS and Finch CA . Red Cell Manual. 6th ed. F.A. Davis Company, Philadelphia,1992:147.
19. Haptoglobin: ARUP Lab Tests. ARUP Laboratories: National Reference Laboratories. 2006-2012. http://www.aruplab.com.
20. Javid J. Human haptoglobins. Curr Top Hematol.1978; 1:151-192.
21.Cazzola M, Guarnone R, Cerani P, Centenara E, Rovati A, Beguin Y. Red blood cell precursor mass as an independent determinant of serum erythropoietin level. Blood. 1998 Mar 15;91(6):2139-2145
22. Skarmoutsou C, Papassotiriou I, Traeger-Synodinos J, Stamou H, Ladis V, Metaxotou-Mavrommati A, Stamoulakatou A, Kanavakis E. Erythroid bone marrow activity and red cell hemoglobinization in iron sufficient beta-thalassemia heterozygotes as reflected by soluble transferrin receptor and reticulocyte hemoglobin in content. Correlation with genotypes and Hb A(2) levels. Haematologica. 2003 Jun;88(6):631-636.
23.Demir A, Yarali N, Fisgin T, Duru F, Kara A Serum transferrin receptor levels in beta-thalassemia trait. J Trop Pediatr. 2004 Dec;50(6):369-371.
24 . Ricchi P, Ammirabile M, Costantini S, Di Matola T, Verna R, Diano A, Foglia MC, Spasiano A, Cinque P, Prossomariti L. A useful relationship between the presence of extramedullary erythropoeisis and the level of the soluble form of the transferrin receptor in a large cohort of adult patients with thalassemia intermedia: a prospective study. Ann Hematol. 2012 Jun;91(6):905-909. doi: 10.1007/s00277-011-1385-y. Epub 2011 Dec 15.
25 Zoi K, Terpos E, Zoi C, Loukopoulos D.. Increased CD177 (PRV1) expression in thalassaemia and the underlying erythropoietic activity. Br J Haematol. 2008 Apr;141(1):100-104. doi: 10.1111/j.1365-2141.2008.06993.x.
26.Camberlein E, Zanninelli G, Détivaud L, Lizzi AR, Sorrentino F, Vacquer S, Troadec MB, Angelucci E, Abgueguen E, Loréal O, Cianciulli P, Lai ME, Brissot P. Anemia in beta-thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression. Haematologica. 2008 Jan;93(1):111-115. doi: 10.3324/haematol.11656.
27. Wang F, Huang W, Li A. Serum haptoglobin suppresses T lymphocyte functions following burns. Chin Med Sci J. 1996 Sep;11(3) :180-183.
28- Vidja PJ, Vachhani JH, Sheikh SS, Santwani PM.. Blood transfusion transmitted infections in multiple blood transfused patients of Beta thalassaemia. Indian J Hematol Blood Transfus. 2011 Jun;27(2):65-69. doi: 10.1007/s12288-011-0057-3. Epub 2011 Apr 11.
29-Elalfy MS, Esmat G, Matter RM, Abdel Aziz HE, Massoud WA.Liver fibrosis in young Egyptian beta-thalassemia major patients: relation to hepatitis C virus and compliance with chelation.Ann Hepatol. 2013 Jan-Feb;12(1):54-61.
30-Said F, El Beshlawy A, Hamdy M, El Raziky M, Sherif M, Abdel kader A, Ragab L.Intrafamilial transmission of hepatitis C infection in Egyptian multitransfused thalassemia patients. J Trop Pediatr. 2013 Aug;59(4):309-313. doi: 10.1093/tropej/fmt017. Epub 2013 Mar 28.
31. Bacq Y, Schillio Y, Brechot JF. De Muret A, Dubois F, Metman EH. Decrease of haptoglobin serum level in patients with chronic viral hepatitis C. Gastroenterol Clin Biol1993;17 (5) :364–369 .abstract .
32.Atta M, Cabral M, Santos G, Paraná R, Atta A. Inflammation biomarkers in chronic hepatitis C: association with liver histopathology, HCV genotype and cryoglobulinemia . Inflamm Res. 2012 Oct;61(10):1101-1106. doi: 10.1007/s00011-012-0502-2. Epub 2012 Jun 21.
33. Aessopos A, Kati M, Farmakis D. Heart disease in thalassemia intermedia: a review of the underlying pathophysiology. Haematologica. 2007 May ;92(5):658-665.
34. Gabay C, Kushner I. Acute phase proteins and other systemic responses to inflamma¬tion. N Engl J Med. 1999 May 11 , 340(6) :448–454.
35.Lo L, Singer ST . Thalassemia : current approach to an old disease . Pediatr Clin North Am. 2002 Dec;49(6):1165-1191, v.
36. Giardina PJ , Grady RW. Chelation therapy in beta-thalassemia: an optimistic update. Seminars in Hematology . 2001 ;38(4):360-366.
37. Langlois M, Delanghe J, DeBuyzere M. Relation between serum IgA concentration and haptoglobin type. Clin Chem.1996 Oct ; 42(10):1722–1723.
38. Dobryszycka W. Biological functions of haptoglobin—new pieces to an old puzzle. Eur J Clin Chem Clin Biochem.1997 Sep ; 35(9) : 647–654.
39. Okazaki T, Nagai T. Difference in hemoglobin-binding ability of polymers among haptoglobin phenotypes. Clin Chem.1997 Oct ;43(10): 2012–2013.