EFFECT OF REPEATED BLOOD TRANSFUSION ON SOME BLOOD PARAMETERS

Document Type : Original Article

Author

Physiology Department, Faculty of Medicine, Al Azhar University (Assuit)

Abstract

Background: Repeated blood transfusion causes a lot of complications in the body specially iron deposition in different organs in the body. Objective: Investigating the changes which occurred in the human body blood parameters on repeated blood transfusion. Subjects and methods: This study was performed at outpatient clinic, Faculty of Medicine, Al-Azhar University Hospital (Assiut). The patients were forty patients already diagnosed as thalassemic major and exposed to repeated blood transfusion and the following parameters were measured (oral glucose tolerance, plasma glucose level, plasma insulin level, C- peptide level, lipase level, serum iron, total iron binding capacity and serum Ferritin). Results: The study showed that hemosidtherosis affected the level of serum lipase which decreased in thalassemic patients as a model of hyperplastic anemia. Also, C-peptide level decreased in those patients more than control. This indicated that the pancreatic functions were affected by iron deposition. Also, serum iron and serum ferritin increased which led to decrease in the level of total iron binding capacity which caused by decrease in Hb level. Conclusion: Blood glucose level increased significantly in thalassemic patients while insulin level decreased in them. Serum Ferritin level was increased in thalassemic patients where the hemoglobin decreased. Serum lipase and C-lipase decreased in thalassemic patient

Keywords


EFFECT OF REPEATED BLOOD TRANSFUSION ON SOME BLOOD PARAMETERS

 

By

 

Maher Abd Al-Shakour

                                                                                                              

Physiology Department, Faculty of Medicine, Al Azhar University (Assuit)

 

ABSTRACT

Background: Repeated blood transfusion causes a lot of complications in the body specially iron deposition in different organs in the body. Objective: Investigating the changes which occurred in the human body blood parameters on repeated blood transfusion. Subjects and methods: This study was performed at outpatient clinic, Faculty of Medicine, Al-Azhar University Hospital (Assiut). The patients were forty patients already diagnosed as thalassemic major and exposed to repeated blood transfusion and the following parameters were measured (oral glucose tolerance, plasma glucose level, plasma insulin level, C- peptide level, lipase level, serum iron, total iron binding capacity and serum Ferritin). Results: The study showed that hemosidtherosis affected the level of serum lipase which decreased in thalassemic patients as a model of hyperplastic anemia. Also, C-peptide level decreased in those patients more than control. This indicated that the pancreatic functions were affected by iron deposition. Also, serum iron and serum ferritin increased which led to decrease in the level of total iron binding capacity which caused by decrease in Hb level. Conclusion: Blood glucose level increased significantly in thalassemic patients while insulin level decreased in them. Serum Ferritin level was increased in thalassemic patients where the hemoglobin decreased. Serum lipase and C-lipase decreased in thalassemic patient

Key words: Thalassemia, repeated blood transfusion.

 

 

INTRODUCTION

     Blood transfusion has many reactions which can be classified into immune reactions due to red blood cells, white blood cells and platelet incompatibilities, and non-immune reactions due to overloading of circulation, massive transfusion, transmission of infection, fat embolism and transfusion siderosis (Tyrrell and Bateman, 2012).

     In repeated blood transfusion to none bleeding patient as, in cases of hyperplastic anemia, the amount of iron in the body get increased (Johnson-Wimbley and Graham, 2011)Baylor College of Medicine, Houston, Texas, USA.

     Circulatory overload is encountered in the transfusion of anemic patients, particularly those with severe and long standing anemia. Those patients must be transfused very slowly and only with packed cells. In some patients, an exchange transfusion has to be carried out to avoid severe congestive heart failure (Pont-Thibodeau et al., 2014).

     There is no doubt concerning the immunosuppressive effect of blood transfusion which has indeed been employed specifically for this purpose in patients before renal transplantation to improve graft survival (Michael et al., 2012)

     Transfusion of bank blood in quantities approaching the patient’s blood volume causes a delusional thrombocytopenia and some degree of clotting factor deficiency, both of which affect haemeostasis adversely. If an amount greater than 50% of the patient’s blood volume is replaced rapidly, the transfusion is deemed massive e.g. five units of blood within one hour in a 70 Kg adult (Mannucci   and  Tripodi, 2013).

    The present work aimed to investigate the changes which occurred in the human body blood parameters on repeated blood transfusion.

SUBJECTS AND METHODS

Subjects: Forty patients (18 male and 22 females) with thalassemia major and fifteen health control children (7males and 8 females) from outpatient clinic, Faculty of Medicine, Al Azhar University Hospital (Assuit). Their age ranged between 10 and 16 years old. Patients were divided into:

Group I (15 person): Healthy control children

Group II (24 patients):  Thalassemia group with intact spleen.

Group III (16 patients): Thalassemia group with splenectomy.

     Informed consents were obtained from all patients and control after explanation of the study and its aim.

Methods: Collection of blood samples were obtained by clean venepuncture (2ml of blood added in plastic tubes containing 2-4 mg of EDTA salt anhydrous dipotassium salt) centrifuged, and exposed to the following tests:

1. Determination of oral glucose tolerance (National diabetes data group, 1979).

2. Determination of plasma glucose level (Watson, 1962).

3. Determination of plasma insulin level (Frier et al., 1981).

4. Determination of C- peptide level (Heding, 1975).

5. Determination of lipase level (Ventrucci et al., 1989).

6. Estimation of serum iron and total iron binding capacity (Tietz, 1976).

7. Estimation of serum ferritin (Addison et al., 1972).

      Data were exposed to student’s t- test, and chi-square using IBM PC micro processor. P value < 0.05 was considered significant.

RESULTS

     The fasting blood glucose level of the thalassemic group with intact spleen was 80.7±10.4 mg/dl, where in control group was 73±7.2 mg/dl, and these results significantly changed, and were not significantly different from the thalassemic group with splenectomy. On the other hand, there was no significant difference between both thalassemic patients in glucose level (Table 1).

     After two hours of glucose ingestion, there was no significant difference between the control group and both thalassemic groups (Table 1).

     There was no significant difference in insulin level between the control group and both thalassemic groups before and after ingestion of glucose.

 

Table (1): Blood glucose level (fasting and post prandial) and insulin level (fasting and after 30 minutes of glucose ingestion).

         Parameters

 

Groups

Mean ± S D

Blood glucose (mg%)

Insulin (IU/ml)

Fasting

Post-prandial

Fasting

After 30 min

Group I (15)

73±7.2

110.5±6.2

5.69±2.77

39.08±2.77

Group II (24)

*80.7±10.4

114.9±9.1

5.39±2.50

30.64±18.12

Group III (16)

*77.4±8.8

111.3±6.2

5.50±2.18

38.25±11.65

 

* Significant

Number of each group was shown in between brackets.

 

 

 

     The number of blood transfusions was significant between both thalassemic groups. Also, the duration of desferol therapy was significant between both thalassemic groups (Table 2).


 

 

Table (2): Frequency of blood transfusion and duration of desferol therapy/year among the studied group.

                      Parameters

 

Groups         

Mean ± S D

Blood transfusion

(times/year)

Duration of desferal therapy (year)

Group I (24)

*16±5.0

+3.7±1.3

Group II (16)

*9±1.8

4.0±1.4

+   Insignificant                       * Significant

Number of each group was shown in between brackets.

 

 

 

     The level of serum iron in the control group was 82.3±11.8 mg/dl, where in the thalassemic group with intact spleen was 179.2±16.5 mg/dl which was significantly higher than the mean serum iron level of the thalassemic group with splenectomy (101.8±17.4 mg/dl -Table 3).

     The mean level of serum ferritin in the control group was 45.5±9.7, and in the thalassemic group with intact spleen was 337.9±63.7 ng/ml which was significantly higher than the serum ferritin in the thalassemic group with splenectomy (Table 3).

     The total iron binding capacity in both thalassemic groups was significantly less than the control group (Table 3).

     The mean hemoglobin concentration in thalassemic group with intact spleen was significantly lower than hemoglobin concentration in thalassemic patients with splenectomy and the control group (Table 3).


Table (3): Levels of serum iron, serum ferritin, total iron binding capacity and hemoglobin.

    Parameters

 

 

Groups

Mean ± S D

Serum iron

(mg/dl)

Serum Ferritin

(mg/ml)

Total iron binding capacity

(mg/dl)

Hemoglobin

(mg/dl)

Group I (15)

82.3±4.8

45.5±9.7

328.2±70.8

13.2±0.3

Group II (24)

179.2±16.5

*337.9±63.7

*238.1±30.3

*5.9±0.8

Group III (16)

*101.8±17.5

*243.3±100.6

*294.9±31.8

*7.3±0.7

Number of each group was shown in between brackets.

 

 

 

     There was a significant decrease in both thalassemic groups compared to the control group, while fasting peptide showed no significant changes compared to control and both thalassemic groups. On the other hand, there was a significant decrease in the level of the serum C-peptide after 30 minutes of glucose ingestion in both groups I, II compared to control group and both thalassemic groups (Table 4).

 

 

 

Table (4): Levels of serum lipase and C- peptide (fasting and before 30 minutes of glucose ingestion).

    Parameters

 

 

Groups

Mean ± S D

Serum lipase

(U/L)

C- peptide (ng/ml)

Fasting

 

After 30 minutes of glucose ingestion

Group I (15)

70.1±25.08

1.17±0.26

4.5±0.74

Group II (24)

*21.62±4.3

1.19±0.24

*3.4±0.52

Group III (16)

*47.7±16.3

1.09±0.26

*3.6±0.6

*Significant

Number of each group was shown in between brackets.

 

 

DISCUSSION

     Thalassemia is a disorder of hemo-globin synthesis. It is characterized by complete absence of globin production, which results in decreased oxygen delivery to the tissues, ineffective erythropoiesis and severe anemia. Patients usually develop complications of chronic anemia including growth retardation (Rachmilewitz & Giardina, 2011 and Gülhan et al., 2016).

     In the present study, the level of blood glucose increased in both groups of the thalassemic patients, where the insulin level was affected slightly especially in the patient with intact spleen. This work was in agreement with the work done by Simeox and McClain (2013) who stated that the risk of development of diabetes in patients with thalassemia who are receiving frequent transfusion has generally been thought to be due to direct toxic effects of iron on the pancreatic islets that lead to insulin deficiency.

     In the present work, the level of serum iron was significantly higher in the thalassemic groups than the control group, and also in the thalassemic group with intact spleen more than that with splenectomy. This could be attributed to the hemosiderosis resulting from frequent blood transfusion (Genc et al., 2016).

     The present study showed that the level of serum ferritin was significantly lower in control group than that of thalassemic patients with splenectomy which was lower than that of patients with intact spleen. These results were in agreement with the finding of Eugene et al, (2011) and Mishra & Tiwari (2013) who reported that the serum iron and ferritin level increased in thalassemic patients, and the increase in the serum iron and ferritin levels may be due to defective iron utilization with increased iron absorption.

     Total iron binding capacity in both thalassemic groups of this work decreased significantly than the control group denoting a full saturation of total iron binding capacity of the patient due to repeated blood transfusion. This was approved before by Verma et al. (2014) who reported that serum level of total iron binding decreased in thalassemic patients than the control.

     The fasting C-peptide level in this work had no significant difference in both thalassemic groups in comparison with control. However, after 30 minutes of glucose ingestion, there was a significant decrease in C-peptide level when compared with control groups. This could be due to reduction in -cells secretion as a result of direct impairment of secretory function by chronic iron overloaded as tissue damage from iron overload (Jones and Hattersley, 2013). The heavy iron deposit was seen in Kupffer cells as in hepatocytes surrounded by fibrosis around the portal tracts. The iron deposition in liver may produce insulin resistance by interfering with the ability of insulin to suppress hepatic glucose production (Kew, 2014).

     This study showed a significant decrease in lipase level in thalassemic patients with intact spleen more than those with splenectomy, and this finding was in agreement with Ashar et al. (2015) who reported that serum lipase is significantly lower in thalassemic children.

REFERENCES

1. Addison, G. M., Beamish, M.R., Haes. C. U. Hdogekin, M., Jacobs, A and Liewellin. J. (1972): An immunoradiometric assay for Ferritin in the serum of normal subjects and patirnts with iron deficiency and iron overload. J. Clin. Path., 25:326-340.

2. Ashar S., Sultan S., Irfan S. M. and Sheeraz A. (2015): Serum fasting lipid profile in children and adolescents with β-thalassaemia major in southern Pakistan. Malaysian J Pathol., 37(3) : 233 – 238.

3. Eugene Y., Leila J., Aakanksha G., Roberta K., Thomas D., Paul H., Thomas G. and John C. (2011): Pulmonary function in thalassaemia major and its correlation with body iron stores. British Journal of Hematology. 155 (1): 102–105.

4. Frier, B. M., Ashby, J. P., Nairn, I. M. and Bairs, J. D. (1981): Plasma insulin, C- peptide and glucagon concentration in patients with insulin independent diabetes treated with chloropamide. Diabetes, 7(1): n45-49.

5. Genc GEOzturk ZGumuslu S and Kupesiz A (2016): Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators. Biol Trace Elem Res., 170 (1):9-16.

6. Gülhan B., Yalçın E., Ünal Ş., Oğuz B., Özçelik U., Ersöz D. Gümrük F. and  Kiper N. (2016): Effects of blood transfusion on cytokine profile and pulmonary function in patients with thalassemia major. Clinical Respiratory Journal, 10 (2): 153–162.

7. Heding, L. G. (1975): Radiommunological determination of human C-peptide in serum. Diabetologia, 29: 321-327.

8. Johnson-Wimbley T D. and Graham D Y.  (2011)Baylor College of Medicine, Houston, Texas, USA:Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol., 4 (3): 177–184.

9. Jones AG and Hattersley AT. (2013): The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med., 30 (7):803-17.

10. Kew MC. (2014): Hepatic iron overload and hepatocellular carcinoma. Liver Cancer, 3(1): 31-40.

11. Mannucci P M and  Tripodi A (2013): Liver disease, coagulopathies and transfusion therapy. Blood Transfus., 11(1): 32–36.

12. Michael R. L., Norah T., Lolu O., Eileen H., James N., Emily B. and Lewis W. T. (2012): Long-Term Management of the Successful Adult Liver Transplant. Liver Transplantation, 19:3-26.

13. Mishra A. K.  and Tiwari A. (2013):  Iron Overload in Beta Thalassemia Major and Intermedia Patients. Maedica (Buchar),m 8 (4): 328–332

14. National diabetes data group (1979): Classi-fication and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes, 28: 1039-45

15. Pont-Thibodeau G.D., Harrington K. and Lacroix J.(2014): Anemia and red blood cell transfusion in critically ill cardiac patients. Ann Intensive Care, 4: 16-22.

16. Rachmilewitz E and Giardina PJ. (2011): How I treat thalassemia? Blood,  118: 3479–3488 

17. Simcox J. A.and McClain D. A.  (2013): Iron and Diabetes Risk. Cell Metab., 5; 17(3): 329–341.

18. Tietz, N. W. (1976): Estimation of serum iron and total binding capacity in fundamental of clinical chemistry, 2nd edition, NW Tietz, ED., Pbl. Saunders, Philadelphia, pp.924-929.

19. Tyrrell CT and Bateman ST (2012): Critically ill children: to transfuse or not to transfuse packed red blood cells, that is the question. Pediatr Crit Care Med., 13:204-10.

20. Ventrucci, M., Pezzilli, R, Gullo, L, Plate, L., Sproviere, G and Barbaro, Nl (1989): Role of serum pancreatic enzyme assays in diagnosis of pancreatic disease. Dig. Dis. Sci., 34:39-45.

21. Verma S., Gupta R., Kudesia M., Mathur A., Krishan G. and Singh S. (2014): Coexisting Iron Deficiency Anemia and Beta Thalassemia Trait: Effect of Iron Therapy on Red Cell Parameters and Hemoglobin Subtypes. Hematology, 5: 30-39.

22. Watson, D. (1962): Enzymatic determination of glucose and easily hydrolysable glucose esters in blood. Anal. Biochemistry, 3:131-140.


 تأثیر نقل الدم المتکرر على بعض قیاسات الدم

ماهر عبد الشکور شعبان

قسم الفسیولوجى- کلیة طب الأزهر (أسیوط)

 

خلفیة البحث: لنقل الدم المتکرر وبکمیات کثیرة تأثیراته الضارة على الجسم و خاصة ظاهرة ترسب الحدید فى أجهزة الجسم المختلفة.

الهدف من الدراسة: دراسة التغیرات التى تحدث على بعض قیاسات الدم من تأثیر نقل الدم المتکرر.

المرضى وطرق البحث:  أجریت هذه الدراسة على المرضى المصابین بأنیمیا البحر الأبیض المتوسط المترددین على العیادات الخارجیة لمستشفى جامعة الأزهر الجامعى بأسیوط. وقد کان عدد المرضى  40. وتم تشخیصهم بأنهم مصابون بأنیمیا البحر الأبیض المتوسط وأنهم قد تعرضوا لنقل دم متکرر وقد أجریت لهم قیاسات العوامل الدم الآتیه ( إختبار تحمل السکر- مستوى الجلوکوز فى الدم - مستوی الإنسولین بالدم - مستوى سی ببتاید فى الدم - مستوى اللیباز - مستوى الحدید -  قیاس قدرة الدم على حمل الحدید - قیاس الفرتیین فى المصل).

النتائج: نتج عن ترسب الحدید إنخفاضا فى إنزیم اللیباز الذى یقل فى مرضى الثلاسیمیا مقارنة بالمجموعة الضابطة- وکذلک یقل نسبة السی بیبتد فى المرضى عنه فى المجموعة الضابطة -وکذلک تبین نتائج هذه الدراسة تأثر البنکریاس بنسبة الحدید المترسب به, وقد زادت نسبة الحدید فى مصل الدم فى المرضى عنه فى المجموعة الضابطة مما أدى إلى زیادة نسبة الفرتین وقلت نسبة إرتباط الحدید مما أدى الى إنخفاض نسبة الهیموجلوبین فى الدم.

 الإستنتاج: إرتفع مستوى السکر فی الدم بشکل ملحوظ فی مرضى الثلاسیمیا فی حین إنخفض مستوى الإنسولین فیها. وکذلک لوحظ زیادة مستوى فیریتین مصل الدم فی مرضى الثلاسیمیا حیث إنخفض الهیموجلوبین. وکذلک إنخفض مستوى اللیباز و سى لیباز فی مریضى الثلاسیمیا.    

 

REFERENCES
1. Addison, G. M., Beamish, M.R., Haes. C. U. Hdogekin, M., Jacobs, A and Liewellin. J. (1972): An immunoradiometric assay for Ferritin in the serum of normal subjects and patirnts with iron deficiency and iron overload. J. Clin. Path., 25:326-340.
2. Ashar S., Sultan S., Irfan S. M. and Sheeraz A. (2015): Serum fasting lipid profile in children and adolescents with β-thalassaemia major in southern Pakistan. Malaysian J Pathol., 37(3) : 233 – 238.
3. Eugene Y., Leila J., Aakanksha G., Roberta K., Thomas D., Paul H., Thomas G. and John C. (2011): Pulmonary function in thalassaemia major and its correlation with body iron stores. British Journal of Hematology. 155 (1): 102–105.
4. Frier, B. M., Ashby, J. P., Nairn, I. M. and Bairs, J. D. (1981): Plasma insulin, C- peptide and glucagon concentration in patients with insulin independent diabetes treated with chloropamide. Diabetes, 7(1): n45-49.
5. Genc GEOzturk ZGumuslu S and Kupesiz A (2016): Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators. Biol Trace Elem Res., 170 (1):9-16.

6. Gülhan B., Yalçın E., Ünal Ş., Oğuz B., Özçelik U., Ersöz D. Gümrük F. and  Kiper N. (2016): Effects of blood transfusion on cytokine profile and pulmonary function in patients with thalassemia major. Clinical Respiratory Journal, 10 (2): 153–162.

7. Heding, L. G. (1975): Radiommunological determination of human C-peptide in serum. Diabetologia, 29: 321-327.
8. Johnson-Wimbley T D. and Graham D Y.  (2011)Baylor College of Medicine, Houston, Texas, USA:Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol., 4 (3): 177–184.
9. Jones AG and Hattersley AT. (2013): The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med., 30 (7):803-17.
10. Kew MC. (2014): Hepatic iron overload and hepatocellular carcinoma. Liver Cancer, 3(1): 31-40.
11. Mannucci P M and  Tripodi A (2013): Liver disease, coagulopathies and transfusion therapy. Blood Transfus., 11(1): 32–36.
12. Michael R. L., Norah T., Lolu O., Eileen H., James N., Emily B. and Lewis W. T. (2012): Long-Term Management of the Successful Adult Liver Transplant. Liver Transplantation, 19:3-26.
13. Mishra A. K.  and Tiwari A. (2013):  Iron Overload in Beta Thalassemia Major and Intermedia Patients. Maedica (Buchar),m 8 (4): 328–332
14. National diabetes data group (1979): Classi-fication and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes, 28: 1039-45
15. Pont-Thibodeau G.D., Harrington K. and Lacroix J.(2014): Anemia and red blood cell transfusion in critically ill cardiac patients. Ann Intensive Care, 4: 16-22.
16. Rachmilewitz E and Giardina PJ. (2011): How I treat thalassemia? Blood,  118: 3479–3488 
17. Simcox J. A.and McClain D. A.  (2013): Iron and Diabetes Risk. Cell Metab., 5; 17(3): 329–341.
18. Tietz, N. W. (1976): Estimation of serum iron and total binding capacity in fundamental of clinical chemistry, 2nd edition, NW Tietz, ED., Pbl. Saunders, Philadelphia, pp.924-929.
19. Tyrrell CT and Bateman ST (2012): Critically ill children: to transfuse or not to transfuse packed red blood cells, that is the question. Pediatr Crit Care Med., 13:204-10.
20. Ventrucci, M., Pezzilli, R, Gullo, L, Plate, L., Sproviere, G and Barbaro, Nl (1989): Role of serum pancreatic enzyme assays in diagnosis of pancreatic disease. Dig. Dis. Sci., 34:39-45.

21. Verma S., Gupta R., Kudesia M., Mathur A., Krishan G. and Singh S. (2014): Coexisting Iron Deficiency Anemia and Beta Thalassemia Trait: Effect of Iron Therapy on Red Cell Parameters and Hemoglobin Subtypes. Hematology, 5: 30-39.

22. Watson, D. (1962): Enzymatic determination of glucose and easily hydrolysable glucose esters in blood. Anal. Biochemistry, 3:131-140.