Serum Lipid Profiles of Patients Having Beta-Thalassemia in a Tertiary Care Hospital
Priyanka Samal1, JatindraNath Mohanty2*, SaurjyaRanjan Das, Sweta Padma Routray2
1Department of Clinical Haematology, IMS and Sum Hospital, SOA deemed to be University, Bhubaneswar, Odisha, India
2Medical Research Laboratory, IMS and Sum Hospital, SOA deemed to be University, Bhubaneswar, Odisha, India
3Department of Anatomy, IMS and Sum Hospital, SOA deemed to be University, Bhubaneswar, Odisha, India
Corresponding Author
Jatindra Nath Mohanty, Assistant Professor, Medical Research Laboratory, IMS and Sum hospital, SOA deemed to be University, Bhubaneswar, Odisha, India
Mail ID- [email protected]
Abstract
Beta-thalassemia is considered to be the most frequent hereditary blood disorder worldwide.
Lipid abnormalities have been detected in different types of beta-thalassemia.This was a cross sectional case control study in which 100 diagnosed cases of Beta thalassemia major were enrolled. 100 healthy children of same age group consisted of control group. The blood samples of study and control groups were examined for lipid profile test and values were evaluated. The tests were done using Olympus AU400 Auto analyser and values were evaluated. Statistical analysis was done by using IBM SPSS version 20. The mean values of serum HDL-C, LDL-C, total cholesterol, TG and VLDL in controls were 47.6±4.3, 76.8
±15.4, 76.8 ±15.4, 74.64±16.23, 22.63±6.6715 mg/dl respectively. Total cholesterol to HDL- C ratio was4.57±1.55 and 2.66±0.39 in cases and controls respectively. Total cholesterol, HDL-C, LDL-C were significantly lower (p<0.05); triglycerides and total cholesterol & HDL ratio were significantly higher (p<0.05) compared with controls.This study concludes that children suffering from beta thalassemia major may possess increased risk of thrombotic and atherogenic complications. Early detection of these patients with deranged lipid profile is required to avoid these complications. It is also important to do routine periodical screening.
Keywords:Beta Thalassemia Major, Lipid Profile, Hypocholesterolemia, hypertriglyceridemia, Thromboembolism.
Introduction
Lipid abnormalities have been detected in different types of beta thalassemia, and also in various hematological disorders including sickle cell disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, spherocytosis, aplastic anemia and myelodysplastic syndrome. [1–4]. The pathogenesis of these abnormalities is not exactly clear, but there are many suggested mechanisms including plasma dilution due to anemia, accelerated erythropoiesis resulting in increased cholesterol uptake by macrophages and histiocytes of the
reticuloen-dothelial system, defective liver functioning due to iron overload, macrophage system activation with cytokine release, and hormonal disturbances.[5,6–8]
It has been estimated that the prevalence of pathological hemoglobinopathies in India is 1.2/1,000 live births, and with approximately 27 million births per year this would suggest the annual birth of 32,400 babies with a serious hemoglobin disorder [6]. Reportedly, there are about 240 million carriers of β-thalassemia worldwide, i.e. 1.5% of world population.
[7,8]. A WHO update on beta- thalassemia in India indicated a similar overall carrier frequency of 3–4%, based on that the current national population would translate to between 35.6 and 47.5 million carriers of the disorder nationwide. The mainstay of treatment of thalassemia is regular blood (Packed Red Blood Cells) transfusions. The major complications of blood transfusion are those related to transmission of infectious agents or development of iron overload [9].
Over the past three decades, regular blood transfusions and iron chelation have dramatically improved the quality of life and transformed thalassemia from a rapidly fatal disease in early childhood to a chronic disease compatible with prolonged life. Today life expectancy of these patients varies between 25-55 years, depending on the compliance with medical treatment.
Despite increased life expectancy, complications keep arising [10]. Various endocrine, cardiac, and hepatic diseases may occur depending, on excessive iron-loading. Thalassemic patients are also subjected to peroxidative tissue injury [11, 12]. Variants of lipoproteins, cholesterol and triglyceride in thalassemic patients show marked oxidative modification due to free radical injury that could represent an event leading to pathogenesis [13]. Free-radical production is increased in patients with iron overload. Hypertryglyceridemia coupled with cardiac iron overload is responsible for many cardiovascular complications seen in these patients. Hence we intent to study the serum lipid profile in the beta thalassemicmajorpatients. So the aim of the study is to assess the serum lipid profileof patients with beta-thalassemia major and compare the findings with healthy control participants.
Materials and methods
A cross-sectional; case control study was done in our tertiary care hospital in a large Metropolitan city. In total;100 diagnosed Cases of beta-thalassemia major in the age group of 1 year to 18 years receiving regular blood transfusions; not suffering from any ailment or any other disease leading to deranged lipid profile were included. In controls; 100 normal healthy children were included. Approval of Institutional Ethical Committee was obtained. After explaining about purpose of study, outcome and explaining that respondent can refuse and withdraw from study at any time in local language an informed consent was taken. All details were recorded in a pre-tested pro-forma which included personal information, transfusion history, clinical examination and lipid profile of the patients. Lipid profiles were done using Olympus AU400 auto analyzer. Statistical analyses were performed by using IBM SPSS Statistics 20.
Results
Out of total 100 cases, 45 were female and 55 were male while out of total 100 controls 41 were female and 59 were male. Mean age of cases was 9.04 ± 4.11 years and of controls was
8.92 ± 4.0 years.Mean weight of cases were 21.59±8.08 Kgs with a mean height of 119.82±21.38 cms and 8.1±0.92 mg/dl Hb level. Mean weight of controls were 29.2±10.4 Kgs with mean height of 132.0±26.3 cms and 12.6±1.07 mg/dl Hb level. All cases had undergone regular blood transfusion. Off the 100 cases, 91 patients (91%) were on Oral chelator therapy, eitherwithDefipirone or Deferasirox. 9 patients were not on any oral chelator therapy.
Study of cases revealed that amongst 100 cases, 99 were having Total Cholesterol within Normal range, while only 1 case showed Total Cholesterol above Normal range i.e.
Hypercholesterolemia. Out of the 100 cases, 86 cases were having low HDL-C while remaining 14 cases were having HDL-C within normal range. Further analysis revealed that out of 100 cases, 98 cases were having LDL-C within Normal range, while only 2 cases were having High LDL-C values (Table 1).
Table. 1: Status of Cholesterol, HDL-C and LDL-C in studied cases Frequency (n=100) Percent Total Cholesterol
Normal 99 99.0
Hypercholesterolemia 1 1.0
HDL-C
Low HDL-C 86 86.0
Normal 14 14.0
LDL-C
Normal 98 98.0
High LDL 2 2.0
out of 100 cases 87 were having normal values of VLDL-C while only 13 cases were having VLDL-C above normal range.Further when triglyceride levels were studied it was found that out of 100 Cases, 51 cases were having normal Triglyceride levels while 49 cases were having Triglycerides above normal range, i.e. Hypertriglyceridemia.
The mean values of the investigated blood lipids both in cases and controls are presented in Table-2 and Table 2 respectively.
Table 2: Analysis of Blood lipids in cases Parameters HDL-C
(mg/dl)
LDL-C (mg/dl)
TC (mg/dl)
TG (mg/dl)
VLDL-C (mg/dl)
TC/HDL Ratio
Mean 26.55 62.11 111.89 112.06 25.58 4.57976
Median 26.00 62.50 113.50 99.50 22.00 4.57576 Std.
Deviation
8.966 21.981 26.749 53.405 21.153 1.558721
Minimum 9 17 47 33 7 2.137
Maximum 53 115 174 345 191 10.143
Table 3: Analysis of blood lipids in control group Parameter
s
HDL-C (mg/dl)
LDL-C (mg/dl)
TC (mg/dl)
TG (mg/dl)
VLDL-C (mg/dl)
TC/HDL Ratio
Mean 47.66 76.84 126.12 74.64 22.63 2.66636
Median 47.00 77.50 128.00 74.00 23.00 2.60682
Std.
Deviatio n
4.384 15.432 15.282 16.234 6.680 .398440
Minimum 41 50 100 50 12 1.906
Maximum 55 99 150 100 35 3.571
Data analysis revealed, mean HDL-cholesterol levels were26.5±8.9 mg/dl in cases and 47.6±4.3 mg/dl in controls; mean LDL-cholesterol levels were 62.1±21.9 mg/dl in cases and 76.8 ±15.4 mg/dl in controls; mean total- cholesterol levels were 111.8 ±26.7 mg/dl in cases and 76.8 ±15.4 mg/dl in controls; mean triglyceride levels were 112.06±53.40 mg/dlin cases and 74.64±16.23mg/dl in controls; VLDL-cholesterol levels were 25.58±21.15mg/dlin cases and 22.63±6.67/dl in controls. Total-cholesterol to HDL-cholesterol ratios were 4.57±1.55 and 2.66±0.39 in cases and controls respectively.
Table 4: Comparison of various parameters of lipid profile in cases and control group
Parameters Cases Control
s
Test value
p value
Mean SD Mean SD
HDL-C 26.5500 8.96613 47.6600 4.38367 -21.151 .000 LDL-C 62.1100 21.98112 76.8400 15.43165 -5.485 .000
TC 111.890
0
26.74908
126.120 0
15.28205 -4.619 .000
TG 112.060
0
53.40541 74.6400 16.23410 6.704 .000 VLDL-C 25.5800 21.15273 22.6300 6.67977 1.330 .185 TC/HDL-C
Ratio
4.5798 1.55872 2.6664 .39844 11.893 .000
Discussion
In this study lipid profile in beta thalassemia children were evaluated &compared it with a group of healthy children. In our study it was found that there is significant difference in between the values of cases and controls. It is seen that in beta thalassemia major Patient’s serum levels of HDL-C, LDL-C and TC is low as compared to controls. In addition of that Triglyceride levels were substantially high. This appears because of many factors. The VLDL-C does not show any significant difference in the values, i.e. neither low nor high.
Results of present study correlate well with previous study [14-19]. Most studies explain the mechanism of alteration in lipid profile of cases. This alteration is likely due to diminished
hepatic biosynthesis as of anemia and iron overload, while a reduced extra hepatic lipolytic activity could account for the rise in circulating TG [14]. Iron-loading and the effects of repeated blood transfusions induce a hepatic acute-phase response, which could determine an LDL-class shift towards protein-rich, denser particles [14,17].
Some authors [15,20-24] suggested that accelerated erythropoiesis and increased uptake of LDL by macrophages and histiocytes of the reticulo endothelial system are the main determinants of low plasma cholesterol levels in beta thalassemia major. Factors such as iron overload (high ferritin level), liver injury, and hormonal disturbances affects lipids pattern among patients with major form of beta-thalassemia, while some researchers observed that the lipid profile in thalassemia major patients is not influenced by age, sex, liver injury, and hemoglobin or ferritin levels [15]. The higher erythroid bone marrow activity with the enhanced cholesterol consumption could be the dominant mechanism implicated in the lipid abnormalities of thalassemia major patients [15, 25]. However other researchers did not find such differences. Study comparing thalassemia major and intermedia demonstrated the lower concentrations of LDL-C found in with beta thalassemia major than with beta thalassemia intermedia patients could be related to the higher level of Hb and ferritin in patients with beta thalassemia major [26]. In thalassemia minor patients; Total cholesterol and LDL-C is lower, authors found nostatistically significant difference in TG, HDL and VLDL among thalassemia minor patients compared to control group [27]. The study also concluded the concentration of Total-C and LDL-C which in thalassemia carriers arebelow the normal levels, which can potentially reduce the risk of cardiovascular diseases. The Lipid-lowering effect of beta-thalassemia trait in minor thalassemiaraises the question as to whether this effect might slow down the progression of coronary diseases and delay the occurrence of myocardial infarction in these patients. This difference in finding is due to different trait studied; minor and major respectively.
Our findings of hypocholesterolemia and hypertriglyceridemia in patients of beta thalassemia major were supported by other studies [28, 29]. Finding of study shows that majority of the patients had blood lipid levels within the normal range, and consequently the prevalence of lipid abnormalities was much lower as compared to the general population of the same age this is contrary to other studies [30]. Same study gives exception of HDL-C which was below normal range. Also, the total-cholesterol to HDL-cholesterol ratio was high in patients, and may underline the importance of this index for the prognosis of future cardiac events in these patients which is in accordance with our study findings [30]. The importance of total- cholesterol to HDL- cholesterol ratio lies in prevention of atherosclerotic disease. The total- cholesterol-to- HDL-C ratio predicts coronary heart disease risk. Higher the ratio the higher is the risk for atherosclerotic and thrombotic complications.
Conclusion
Lipid profile in Beta thalassmia patients show essentially low degrees of absolute cholesterol, LDL-C and HDL-C. There was increment in triglyceride levels and complete cholesterol/HDL-C proportion. VLDL-C levels were typical in these patients. From above perceptions it very well may be presumed that youngsters experiencing Beta thalassemia Major may have expanded danger of cardiovascular thrombotic malady and thrombotic intricacies in different organs. Since it is difficult to foresee these progressions clinically
subsequently an ordinary blood lipid profile ought to be consistently done in patients with beta thalassemia major.
Reference
1. Louis C.K. Low. Growth of children with beta thalassemia major. Indian J Pediatr2005 Feb; 72:159-160.
2. Verma IC, Choudhry VP, Jain PK. Prevention of thalassemia: A necessity in India. Indian J Pediatr 1992; 59:649-654.
3. Agarwal, S., A. Gupta, U. R. Gupta, S. Sarwai, S. Phadke, and S. S. Agarwal.
"Prenatal diagnosis in beta-thalassemia: an Indian experience." Fetal diagnosis and therapy 18, no. 5 (2003):328-332.
4. Modell, Bernadette, and MatthewDarlison. “Global Epidemiology of Haemoglobin Disorders and Derived Service Indicators.” Bulletin of the World Health Organization 86.6 (2008):480–
487. PMC. Web. 14 Dec. 2014.
5. Madan, N., Sharma, S., Sood, S. K., Colah, R., & Bhatia, (Late) H. M. (2010).
Frequency of β-thalassemia trait and other hemoglobinopathies in northern and western India. Indian Journal of Human Genetics, 16(1), 16–25.
doi:10.4103/0971- 6866.64941
6. Galanello R, Eleftheriou A, Traeger- Synodinos J, Old J, PetrouM, Angastiniotis M. In: Princeton of Thalassaemias and other Haemoglobin- opathies. 2003. Annex 1: Globalepidemiological data tables; pp.148–53.
7. Yaish HM. Thalassemia. http://
www.emedicine.com/PED/topic2229.htm Accessed as on date 6th August2013.
8. Verma IC, Choudhry VP, Jain PK. Prevention of thalassemia: A necessity in India. Indian J Pediatr 1992; 59:649-654.
9. Roberts D.J., Brunskill S.J., Deree C. Oral Deferiprone for Chelation in children with Thalassemia. National Blood Service, Systematic Review Initiative, UK OX3 9BQ.
10. Grow, Kirti, MinakshiVashist, PankajAbrol, Shiksha Sharma, and RituYadav. "Beta Thalassemia inIndia:Current Status and the Challenges Ahead." International Journal of Pharmacy & Pharmaceutical Sciences 6, no. 4 (2014).
11. Arıca, Vefik, Seçil Arıca, CahitÖzer, and Murat Çevik. "Serum Lipid Values in Children with Beta Thalassemia Major." PediatTherapeut 2, no. 130 (2012):
2161-0665.
12. Shamshirsaz, Alireza A., Mir Reza Bekheirnia, Mohammad Kamgar, NimaPourzahedgilani, NavidBouzari, Moha- mmadrezaHabibzadeh, Reza Hashemi et al. "Metabolic and endocrinelogic complications in beta- thalassemia major: a multicenter study in Tehran." BMC Endocrine Disorders 3, no. 1 (2003): 4.
13. Omran, DakhelGhani. "Lipid Profile in Children with Beta–Thalassemia Major in Babylon."
14. Al-Quobaili, Faizeh A., and Imad E. AbouAsali. "Serum levels of lipids and lipoproteins in Syrian patients with beta- thalassemia major." Saudi medicaljournal 25, no. 7 (2004): 871-875.
15. Mansi, Kamal M., and Talal A. Aburjai. "Lipid Profile in Jordanian Children with ß-thalassemia Major." International Journal of Hematology and Oncology 18 (2008): 93-98.
16. Patne, A. B., P. J. Hisalkar, and S. B. Gaikwad. "Lipid Abnormalities in Patients of Beta Thalassaemia Major. "IJPBS, vol(2),issue 2,April- June(2012);106-112
17. Arıca, Vefik, Seçil Arıca, CahitÖzer, and Murat Çevik. "Serum Lipid Values in Children with Beta Thalassemia Major." PediatTherapeut 2, no. 130 (2012):
2161- 0665.
18. Khubchandani, Asha, Viral Solanki, VijaysinhParmar, MeghanaSolanki, Jaimin Patel, and SagarGangwani. "Estimation of Serum lipid profiles in patients with Beta-thalassemia major."
19. KhaleedJumaa K., Abeer A.A., MaysemM.Alwash, Nahi Y. Yaseen, Ahmed M.Hamza “Biomarkers and trace elements in beta thalassemia major.” Iraqi Journal of Cancer and Medical Genetics.
20. Maioli, M., G. B. Cuccuru, P. Pranzetti, A. Pacifico, and G. M. Cherchi.
"Plasma lipids and lipoproteins pattern in beta- thalassemia major."
Actahaemat- ologica 71, no. 2 (1984): 106-110.
21. Maioli, Mario, SilvestroPettinato, Gian Mario Cherchi, DomenicoGiraudi, Adolfo Pacifico, Giuseppe Pupita, and Massimo GB Tidore. "Plasma lipids in beta- thalassemia minor." Atherosclerosis 75, no. 2 (1989): 245-248.
22. Maioli, Mario, Giovanni B. Vigna, Giancarlo Tonolo, PatriziaBrizzi, MilcoCiccarese, Paola Donegà, MargheritaMaioli, and Renato Fellin. "Plasma lipoprotein composition, apolipoprotein (a) concentration and isoforms in<i>
β</i>-thalassemia." Ather- osclerosis 131, no. 1 (1997): 127-133.
23. Christina C, Demosthenes B, Christos P. Distributionof serum lipids and lipoproteins in patients with beta thalassemia major; an epidemiological study in young adults from Greece.Lipids in Health and Disease 3: 328-334, 2004.
24. Goldfarb AW, Rachmilewitz EA, Eisenberg S. Abnormal low and highdensity lipoproteins in homozygous beta-thalassaemia. Br J Haematol. 1991;79:481- 486.
25. Amendola, G., P. Danise, N. Todisco, G. D'urzo, A. Di Palma, and R. Di Concilio. "Lipid profile in β‐thalassemia intermedia patients: correlation with erythroid bone marrow activity." International journal of laboratory hematology29, no. 3 (2007): 172-176.
26. Ragab, S. M., M. A. Safan, and A. S. Sherif. "Lipid profiles in β thalassemic children." Menoufia Medical Journal 27, no. 1 (2014): 66.
27. Hashemieh, M., M. Javadzadeh, A. Shirkavand, and K. Sheibani. "Lipid profile in minor thalassemic patients: a historical cohort study." Bangladesh Medical Research Council Bulletin 37, no. 1 (2011): 24-27.
28. Shams, Sedigheh, Mohammad TaghiHaghiAshtiani, Maryam Monajemzadeh, LeiliKoochakzadeh, HeshmatIrani, FahimehJafari, and AmenehMohseni.
"Evaluation of Serum Insulin, Glucose, Lipid Profile, and Liver Function in β- Thalassemia Major Patients and Their Correlation With Iron Overload." Lab Medicine 41, no. 8 (2010): 486-489.
29. Chand SK, Nanda S, Rout E, Mohanty JN, Mishra R, Joshi RK. De novo sequencing and characterization of defensetranscriptome responsive to Pythiumaphanidermatum infection in Curcuma longa L. Physiological and Molecular Plant Pathology. 2016 Apr 1;94:27-37.
30. Ferdaus, Mohammed Zubaerul, A. K. M.M. Hasan, and HossainUddinShekhar.
"Analysis of serum lipid profiles, metal ions and thyroid hormones levels abnormalities in β-thalassaemic children of Bangladesh." JPMA. The Journal of the Pakistan Medical Association 60, no. 5 (2010): 360.
