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ORIGINAL ARTICLE
Year : 2018  |  Volume : 21  |  Issue : 1  |  Page : 37-41

Evaluation of glucose-6-phosphate dehydrogenase activity and hematological changes in psychotic patients undergoing antipsychotic chemotherapy in Benin City


Department of Medical Laboratory Science, School of Basic Medical Sciences, College of Medical Sciences, University of Benin, Benin City, Nigeria

Date of Web Publication21-May-2018

Correspondence Address:
Dr. Evarista Odaburhine Osime
Department of Medical Laboratory Science, School of Basic Medical Sciences, College of Medical Sciences, University of Benin, Benin City
Nigeria
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DOI: 10.4103/smj.smj_51_16

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  Abstract 


Background: Drug-induced hemolytic anemia can be life threatening and may pose a threat to the management and disease progression of some illnesses. The aim of this work is to evaluate changes in hematologic parameters and glucose-6-phosphate dehydrogenase (G6PD) activity in psychotic patients undergoing antipsychotic chemotherapy. Materials and Methods: A total of 70 participants comprising of 35 psychotic patients (21 males and 14 females) with mean age of 40.5 ± 5 years as test participants and 35 apparently healthy nonpsychotic individuals (20 males and 15 females) with mean age of 25.5 ± 1.5 years as controls were used for this study. G6PD was estimated spectrophotometrically using Randox G6PD assay kit while the hematological parameters were determined using the Erma hematology autoanalyzer. Morphology of the blood samples was manually done by making a thin film stained by Leishman stain and examined microscopically using the oil immersion objective. Results: G6PD activity was found to be higher in test participants (P = 0.075) when compared to the control group. Its activity was also observed to be higher in females when compared to the males (P = 0.051). Hemoglobin concentration, hematocrit, values, mean cell volume, and mean cell hemoglobin were observed to be lower in test participants when compared to the controls (P< 0.05, P = 0.001, P = 0.022, and P = 0.044, respectively). There were no significant differences in total white blood cell counts (WBCs), lymphocytes, granulocytes, platelet count, and red cell distribution width in test participants when compared to controls (P = 0.177, P = 0.665, P = 0.086, P = 0.159, and P = 0.060, respectively). Conclusion: There are changes in hematologic parameters using antipsychotic drugs, and these changes may predispose an individual to iron deficiency anemia and to hemolytic episodes.

Keywords: Glucose-6-phosphate dehydrogenase, hematologic, psychosis


How to cite this article:
Osime EO, Onuigbo FE, Samuel SC. Evaluation of glucose-6-phosphate dehydrogenase activity and hematological changes in psychotic patients undergoing antipsychotic chemotherapy in Benin City. Sahel Med J 2018;21:37-41

How to cite this URL:
Osime EO, Onuigbo FE, Samuel SC. Evaluation of glucose-6-phosphate dehydrogenase activity and hematological changes in psychotic patients undergoing antipsychotic chemotherapy in Benin City. Sahel Med J [serial online] 2018 [cited 2018 Jun 19];21:37-41. Available from: http://www.smjonline.org/text.asp?2018/21/1/37/232783




  Introduction Top


Psychosis can be referred to as a state of altered consciousness that prevents the integration of information into reality.[1] It is a serious but treatable medical condition affecting the brain associated with some loss of contact with reality and can dramatically change a person's thoughts, beliefs, and perceptions. These conditions include schizophrenia, depression, bipolar, and substance abuse.[2] Antipsychotic agents constitute a class of drugs used to treat psychotic disorder as well as other mental and emotional conditions which are primarily composed of major tranquilizers.[3] These antipsychotics are classified into typical/ first-generation antipsychotics including phenothiazines (e.g., chlorpromazine), butyrophenones (e.g., haloperidol), and thioxanthenes (e.g., flupentixol) and a typical/second-generation antipsychotics including clozapine, risperidone, olanzapine, quetiapine, and aripiprazole.

Studies reveal that the use of certain antipsychotic agents results in hematological dyscrasias among which are leukopenia, neutropenia, thrombocytopenia, anemia, and leukocytosis [4] which may present a major problem in the management of resistant psychotic patients who do not respond to both conventional and novel antipsychotics.

Glucose-6-phosphate dehydrogenase (G6PD) is referred to as cytoplasmic enzyme that is distributed widely in all cells. It catalyzes the first step in the hexose monophosphate pathway.[5] Its activity results in the production of antioxidants that protect cells against oxidative damage. The red cells are exquisitely sensitive to oxidative damage in the absence of reduced activity of G6PD as they lack other nicotinamide adenine dinucleotide phosphate oxidase-producing enzymes. G6PD deficient individuals are asymptomatic until they are exposed to oxidative stress produced by the taking of certain drugs, metabolic conditions, infections, and ingestion of some foods resulting in acute hemolytic anemia.[6] This study is aimed at investigating the effects of antipsychotic drugs on some hematological parameters and G6PD activity with a view of assessing those factors that may predispose them to hemolytic anemia.


  Materials and Methods Top


Subjects selection

This was a case–control study comprising of 70 participants. Thirty-five psychotic patients (21 males and 14 females) on antipsychotic drugs of up to 3 months and above at the Federal Neuro-Psychiatric Hospital, Benin City, with a mean age of 45 ± 5 years were used as test participants while the controls were 35 apparently healthy nonpsychotic individuals (20 males and 15 females) with mean age of 25.5 ± 1.5 years. This study was conducted between January and June 2016.

Sample collection and analysis

Venous blood (4.0 ml) was collected from each participant into ethylenediaminetetraacetic acid specimen bottles and taken to the laboratory for analysis. Hematological parameters were analyzed using the hematology Erma autoanalyzer. The morphology of the red cells was examined by making a thin film from the blood samples, allowed to air-dried and stained with Leishman stain for 7 min. Slides were then washed, allowed to air-dried, and examined microscopically using the oil immersion objective. G6PD was estimated using the Randox G6PD assay kit spectrophotometrically. Briefly, 0.2 ml of each blood sample was washed three times in 2 ml normal saline for 10 minutes, and the cells were resuspended in 0.5 ml of reagent 4 (R4), allowed to stand for 15 minutes, and recentrifuged to get the hemolysate. From the hemolysate, 50 μl was pipetted into a test tube, 3 ml of reagent 1 (R1) added, and 100 μl of reagent 2 (R2) was then added. It was mixed and incubated for 5 min at 37°C. Reagent 3 (R3) was added and the absorbance read spectrophotometrically at 340 nm.

Statistical analysis

Data generated were analyzed using the IBM statistical software SPSS version 20 (Armonk, New York). The mean standard deviation, probability value (P), and level of significance were gotten using independent sample t-test while one-way analysis of variance was used to analyze the variation in the mean values for the various age groups. Statistical significance was set at P < 0.05, highly significant at P < 0.001, and not significant at P > 0.05.

Ethical consideration

Ethical approval was obtained from Ethics Committee of Federal Neuro- Psychiatric Hospital, Benin City on 15th April 2016. Informed written consent was obtained from the patients.


  Results Top


This shows a lower hemoglobin concentration, hematocrit value, mean cell volume (MCV), and mean cell hemoglobin (MCH) between test and control participants (P< 0.005, P = 0.001, P = 0.022, and P = 0.044, respectively). There were no significant changes in total WBC, lymphocytes, granulocytes, and platelet counts between test and control participants (P = 0.177, P = 0.663, P = 0.086, and P = 159, respectively). Blood film picture showed more microcytic hypochromic cells in test participants when compared to the controls, and G6PD activity was found to be higher in test participants when compared to controls although not statistically significant (P = 0.075, P > 0.05) [Table 1]. It was higher in females in comparison with the males (females 236 ± 70, males 185 ± 76) though this higher value was not statistically significant (P = 0.050, P > 0.05). [Table 2] shows the haematological parameters of male and female subjects. Erythrocytes concentration increased significantly in males when compared to females (P < 0.05). In [Table 3] the haematological variations in the different age brackets in test and control subjects were expressed and there were no significant changes in all of the parameters (P > 0.05). There was no significant difference in G6PD activity among the different age groups (P = 0.828, P > 0.05) as shown in [Table 4]. Although G6PD activity increased in females when compared to males, these increase was not statistically significant (P > 0.05) as shown in [Table 5]. Variation in RBC and G6PD among the different age brackets in test subjects were expressed in [Table 6]. It showed no significant difference in the different age brackets (P ≥ 0.05).
Table 1: Hematological parameters in test and control participants

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Table 2: Hematological parameters of male and female participants

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Table 3: Variation in hematological parameters with age in test participants

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Table 4: Changes in red blood cell and glucose-6-phosphate dehydrogenase in test and control groups

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Table 5: Differences in red blood cell and glucose-6-phosphate dehydrogenase among male and female test participants

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Table 6: Variation in red blood cell and glucose-6-phosphate dehydrogenase among different age groups in test participants

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  Discussion Top


The data obtained from this present study showed that antipsychotic therapy caused a significant decrease in hematocrit and hemoglobin levels in the test participants; this may be attributed directly to the impact of the drugs which makes these patients inactive thereby reducing erythropoietic activity in such individuals. This agrees with earlier research studies,[7] which showed a significant level of reduced hematocrit and hemoglobin levels in these individuals. Hematological indices including MCH, MCV, and MCH concentration (MCHC) are absolute values that give information about the severity of anemia.[8] It was observed in this study that there was a significant increase in MCV and MCH while MCHC though increase was not significant. This also agrees with earlier work.[9] They attributed this increase to a high level and activity of liver enzymes such as the gamma-glutamyltransferase and transaminases. This may show the toxic effects of the drugs on microsomal structures in the liver cells associated with intrahepatic obstruction of bile flow by drugs such as chlorpromazine as indicated by Henderson and Moss.[10] They observed an increase in liver enzymes secondary to antipsychotic medications and those may have minimal effect in the red cells resulting in the appearance of moderately large red cells associated with the increased hematological indices.[11]

On examination of the peripheral blood film, we observed a significant level of microcytic hypochromic red blood cells. This may be indicative of an impending iron deficiency anemia which may be due to the antipsychotic drugs modulating the iron levels.[12],[13] Various researches have shown that antipsychotic drugs can negatively impact iron status in individuals due to its chelation abilities.

The hemoglobin concentration and packed cell volume of the female on antipsychotic drugs showed a significant decrease when compared to the males also on these drugs. This may be attributed to physiological changes in women such as menstruation and other changes in the hormone secretion in the females. There was a reduction in the total WBC with a reduced neutrophil count and increased lymphocyte count. This could be attributed to the reduced immune states of the psychotic patients. This, however, is in contrast to other researchers that recorded higher WBC.[14] G6PD, a cytoplasmic enzyme widely distributed in all cells, helps to maintain the integrity of the red cell membrane additionally to its primary function of catalyzing the first step of the pentose phosphate pathway.[15] In this study, G6PD activity was observed to be higher in the test group when compared to the controls, although not significant. This may be attributed to the effect of the illness on the normal functioning of the brain cells as it is known that the brain is one of the organs with the highest activity of G6PD in normal humans.[15] The reduced levels of G6PD recorded would cause red blood cells to counter balance oxidative stress exposing them to intravascular hemolysis. The rate of G6PD deficiency was observed to be higher in males than females, although not significant. This may be attributed to the X-linked pattern of inheritance with males which may have only one X chromosome unlike females having two X chromosome. Thus, the prevalence of G6PD deficiency in any population is determined by the number of deficient males.[16]


  Conclusion Top


The results obtained from this present study have shown that the use of antipsychotic drugs (such as chlorpromazine, risperidone, amitriptyline, diazepam, and carbamazepine) can cause a decrease in hemoglobin concentration, packed cell volume, MCV, and MCH which could result in iron deficiency anemia. This study also reports a reduced activity of G6PD in the test group when compared to the controls which may predispose them also to hemolytic anemia.

Acknowledgment

We acknowledge the assistance of the clinicians and nurses at the Federal Neuro-Psychiatric Hospital, Uselu, Benin City, for their assistance in the collection of blood samples.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Beers MH, Robert B. Psychiatric Emergency, the Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories; 2002. p. 205-10.  Back to cited text no. 1
    
2.
Canadian Mental Health Association. A Siblings Guide to Psychosis: Information, Ideas and resources. Toronto: Canadian Mental Health Association; 2005. p. 342-9.  Back to cited text no. 2
    
3.
Ford-Martin PA. Gale Encyclopedia of Medicine. 2nd ed. USA: The Gale Group Inc.; 2004.  Back to cited text no. 3
    
4.
Patterson BD, Jennings JL. Spiking fever and profuse diarrhea with clozapine treatment. Am J Psychiatry 1993;150:1126.  Back to cited text no. 4
    
5.
Luzzatto L. Glucose-6 – Phosphate dehydrogenate deficiency: From genotype to phenotype. Haematologica 2006;91:1303-6.  Back to cited text no. 5
[PUBMED]    
6.
Cappellini MD, Fiorelli G. Glucose-6 – Phosphate dehydrogenase deficiency. Lancet 2008;371:64-74.  Back to cited text no. 6
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7.
Wasti A, Ghani R, Manji MA, Ahmed N. Haloperidol induced varlations in hematological indices. Pak J Med Sci 2004;20:197-200.  Back to cited text no. 7
    
8.
Raphael SS. Practice of hematology. Lynch's Medical Laboratory Technology. 4th ed. Philadelphia: W.D. Saunder's Company; 1983. p. 696-7.  Back to cited text no. 8
    
9.
Akanni EO, Raji AA, Eegunranti BA, Bamisaye EO, Sodipe O. Effects of antipsychotic chemotherapy on haematological parameters of psychotic patients in Lautech Teaching Hospital, Osogbo, Nigeria. Br J Pharmacol Toxicol 2011;2:104-7.  Back to cited text no. 9
    
10.
Henderson AR, Moss HD. Enzyme. In: Tietz Fundamentals of Clinical Chemistry. 5th ed., Vol. 20. Philadelphia USA: HB Saunders Company, a Harcourt Sciences Company; 2001. p. 352 89.  Back to cited text no. 10
    
11.
Harold IK, Benjamin JS. Drug dependence. In: Comprehensive Textbook of Psychiatry. Vol. 22. Baltimore, USA: Williams & Wilkins; 1985. p. 1016-20.  Back to cited text no. 11
    
12.
Prentice H, Victoria E, Dembranvolle MA. The complete blood count. Best East Mediterranian Health J 2001;12:627-52.  Back to cited text no. 12
    
13.
Inuwa IM, Zaidan Z, Viernes N. White ultra structure before and during antipsychotic therapy in schizophrenia. J Anat 2004;204:227-38.  Back to cited text no. 13
    
14.
Seifert RD. Therpeutic drug monitoring: Psychotropic drugs. J Pharm Pract 1984;6:403-16.  Back to cited text no. 14
    
15.
Ademowo OG, Falusi AG. Molecular epidemiology and activity of erythrocyte G6PD variants in a homogenous Nigerian population. East Afr Med J 2002;79:42-4.  Back to cited text no. 15
[PUBMED]    
16.
Acero LH. Glucose 6 – Phosphate dehydrogenase enzyme deficiency among infants: An eye opener to parents and would be parents. Int Proc Chem Biol Enviro Eng (IPCBEE) 2012;49:23-5.  Back to cited text no. 16
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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