31.7.2 Etiological Profile of Pancytopenia in Children Visiting Qazi Hussain Ahmad Medial Complex Nowshera

Original Article

 

Pancytopenia in Children

Etiological Profile of Pancytopenia in Children Visiting Qazi Hussain Ahmad Medial Complex Nowshera

Bibi Aalia1, Irfan Khan2, Khalid Khan2, Khalil Ahmad2, Irfan Ullah2 and
Muhammad Shafiq2

                                                   ABSTRACT

Objective: To find the etiological profile of pancytopenia in children visiting Qazi Hussain Ahmad Medical Complex Nowshera.

Study Design: Cross sectional study

Place and Duration of Study: This study was conducted at the Department of Pediatrics, Qazi Hussain Ahmad Medical Complex, Nowshera from January to December 2019.

Materials and Methods: Total 119 patients were included in the research. After applying inclusion and exclusion criteria, blood samples were tested in the hospital laboratory. Bone marrow biopsy was done in selected patients according to provisional diagnosis. Data was analysedusing SPSS version 21.

Results: Total 119 (55%male and 45%female) patients with mean age6 years + 15.84were recruited. 2% patients had malaria, 8% patients had enteric fever, 15% patient’s leishmaniasis, 50% megaloblastic anemia, 10% aplastic anemia, and 15% of patients had leukemia.

Conclusion: Pancytopenia is a common problem in both settings, clinical and hematological practice. Many other comorbidities also present in patients with pancytopenia. It is imperative to recognize the most common etiologies of pancytopenia among patients belong tolocal community because few are entirelytreatable while in others morbidity is reduced  and survival is prolonged.

Key Words: Pancytopenia, Bone marrow aspiration, Megaloblastic anemia, acute Leukemia.

Citation of article: Aalia B, Khan I, Khan K, Ahmad K, Irfan Ullah, Shafiq M. Etiological Profile of Pancytopenia in Children Visiting Qazi Hussain Ahmad Medial Complex Nowshera. Med Forum 2020;31(7):7-11.

 

 

INTRODUCTION

One of the most common clinico-hematological problem is pancytopenia, which is associated with various diseases in children1.There is a reduction in three blood cell lines including white blood cells, red blood cells and platelets below normal values2.Pancytopenia can be due to a decrease production of stem cells in bone marrow or peripheral destruction of cells. The decrease in cell production can occur due to infections, drugs, toxins and malignant cells infiltration leading to hypo cellular bone marrow.

 

 

1. Department of Pediatrics, Khyber Institute of Medical Sciences, Kohat.

2. Department of Pediatrics, Nowshera Medical College, Nowshera / Qazi Hussain Ahmad Medical Complex, Nowshera.

 

 

Correspondence: Dr. Bibi Aalia, Assistant Professor of Pediatrics, Khyber Institute of Medical Sciences, Kohat.

Contact No: 0333-5153856

Email: dr.alia87@hotmail.com

 

 

Received:    February, 2020

Accepted:    March, 2020

Printed:        July, 2020

 

 

 

 

 

Clinical presentation varies from mild pallor to severe anemia, infections; bleeding tendencies including petechiae, bruises, and bleeding in vital organs leading to life-threatening emergencies.

Pancytopenia has multiple causes, butthe frequency of these causes is reported in limitedstudies. Most common causes reported in children are aplastic anemia, megaloblastic anemia, infections like malaria, enteric fever, leishmaniasis, Fanconi anemia, acute lymphoblastic leukemia and myelodysplastic syndrome.1the etiology varies in various populations depending on difference in age pattern, and nutritional status and prevalence of infections2.The severity of underlying pathology and pancytopenia will determine the prognosis. Knowing the exact cause helps in treating appropriately. There are different trends in its clinical pattern, treatment modalities,and outcome which needs to be kept in mind while managing it3. A study from United States showed infection as the most common cause4.Indianstudy also shows that infections as one of the commonest cause of pancytopania5. Leishmaniasis was the leading cause of febrile pancytopenia in an endemic area6.In developing countries,kala-azar, Malaria, enteric fever, bacterial sepsis, Megaloblastic and Aplastic anemia are also causes of pancytopania7. Megaloblastic anemia is the leading cause of pancytopenia in developing countries like Pakistan in a study,andits incidence can be reduced by treatment of water like filtration and chlorination8.In another study in Pakistan, acute leukemia was among the most common aetiologies9,10.

Aplastic anemia is hematopoietic stem cell disorder resulting in pancytopenia and hypocellular bone marrow. Most cases are usually acquired and have immune-mediatedpathophysiology. A study from China showed aplastic anemia the most common cause in 52% cases11. A study conducted in India showed aplastic anemia as one of the frequent cause (33.8%)12. The prevalence of aplastic anemia was reported as 20% in a Pakistani study13.

MATERIALS AND METHODS

The cross sectional study was done at Pediatric Department, Qazi Hussain Ahmad medical complex Nowshera from January to December 2019.

Total sample sizeof n=119was estimated byapplying the “WHO software for sample size calculation in health studies”fixing thefollowing:

Confidence interval = 95%

Expectedpercentage of etiological factor that is aplastic anemia in pancytopenia.8 = 18.6%

Absolute precision = 10%.

Moreover,consecutive(non-probability sampling) were used for sample collection. Patients of age group 3 months to 15 years with pancytopenia as per operational definitionwere included while patients who are already receiving treatment for different diseases like aplastic anemia and leukemiawere excluded.This studywas continued aftertaking approval fromthe  ethical board. Consent form was obtained from either parents or attendants was taken. A detailed history and examination were done,and hematological parameters were recorded on a proforma. Investigations were done in the hospital laboratory. Bone marrow biopsy was done in selected patients according to provisional diagnosis. Data were entered into a computer and analysed using SPSS v. 21. Quantitative variables like age, TLC,platelets& hemoglobin wereestimated as mean ± standard deviation.Sex and etiological profile of Pancytopenia which are categorical variable were presented as frequency (%).

RESULTS

Among n=119(100%) n=65 (55%) patient were male while n=54(45%) were female. Mean age of 6+ 15.84 years and n=71(60%) patients had age ranged from 1-5 years=36(30%) 6-10 years,andn=12(10%) 11-15 years. (Table 1).

Their mean Hb level was 6.85+1.833g/dl. Among them, n=30(25%) patients ranged 3-4g/dl and n=89(75%) had 5-10 g/dl. Whereas, mean TLC was 2818.7+ 3746.9/mm3. Of total, n=71(60%) patients had was 1500-2500/mm3, and n=48(40%) ranged 2500-4000/mm3.Platelet count was analyzed as n=65(55%) patients had 20, 000-100,000/mm3, n=54(45%) had100,00-150,000/mm3.Meancount was44040.0+43318.8/mm3. (Table 2).

Table No. 1. Age and gender distribution. (n=119)

Age 

Frequency

Percentages

1-5 years

71

60%

6-10 years

36

30%

11-15 years

12

10%

Gender

Frequency

Percentage

Male

65

55%

Female

54

45%

Total

119

100%

Table No. 2: Hemoglobin level and total leukocyte count platelet count  

Hemoglobin  Level 

Frequency

Percentage

3-4  

30

25%

5-10 

89

75%

 

 

1500 -2500 

71

60%

2500-4000

48

40%

 

 

20,000-100,000  

65

55%

100,000-150,000 

54

45%

Total

119

100%

 

Figure No,1. Etiological Profile.(n=119)

Table No. 3. Stratification of etiological profile with age groups.

Etiological profile

1-5 years

6-10 years

11-15 years

Total

Malaria

1

(0.84%)

1

(0.84%)

0

(0.0%)

2

(1.68%)

Enteric fever

6

(5.04%)

3

(2.52%)

1

(0.84%)

10

(8.40)

Leishma-niasis

11

(9.24%)

5

(4.20)

2

(1.68%)

18

(15.12%)

Megalo-blastic anemia

35

(29.41%)

18

(15.12%)

6

(5.04%)

59

(49.58%)

Aplastic anemia

7

(5.88%)

4

(3.36)

1

(0.84%)

12

(10.09%)

Leukemia

11

(9.24%)

5

(4.20)

2

(1.68%)

18

(15.13%)

Total

71

(59.66%)

36

(30.26%)

12

(10.08%)

119

(100%)

Etiological profile of n=119(100) ensued in n=2(2%) malaria, n=10(8%) enteric fever, n=18(15%) Leishmaniasis, n=59(50%) Megaloblastic anemia, n=12(10%) Aplastic anemia, and n=18(15%) with Leukemia. (Figure 1).

statistically significant difference was found between age groups and etiological profile (p = 0.003). It was megaloblastic anemia which was more prevalent n=59(49.58%), especially on youngest patients, aged 1-5 years i.e.=35 (29.41%). Table 3.

 

 

 

Table No. 4: Stratification of etiological profile with hemoglobin level

 

 

Malaria

Enteric fever

Leish-maniasis

Megalo-blastic anemia

Aplastic anemia

Leukemia

Total

P-Value

Hemoglobin

3-4

0

3

5

15

3

4

30

0.003

5-10

2

7

13

44

9

14

89

TLC

1500 -2500 

2

6

11

34

7

11

71

0.003

2500-

4000 

0

4

7

25

5

7

48

Platelet Count 

20,000-100,000  

2

6

9

32

7

9

65

0.002

 

100,000-150,000 

0

4

9

27

5

9

54

 

 

 

                        Chi-square test - P value was 0.002

Figure No.2: Genderwisecolumn and bar chart of the etiological profile.

 

 

 

DISCUSSION

Pancytopenia is one of the common hematological problem of children in the out-patient department. A clinician must consider it when a patient presents with a triad of symptoms i.e. prolonged fever, unexplained pallor, and bleeding tendency. Bone-marrow is frequently used investigation for pancytopenia. It isa safe invasive procedure, with low risk of bleeding even in pancytopenic patient. The slightly lower percentage of nutritional anemia in our study is due to the fact that we only choose thepancytopenic patients and iron deficiency anemia alone was not found to cause pancytopenia while in the study done by Rahimet al the frequency of iron deficiency anemia was 3.53%. In a study in Yemen, a total of 75 pancytopenic patients were studied. Iron deficiency anemia as a cause of pancytopenia was found in only 1 (1.3%) patient14.

In the study of Rahim et al. 32.55% cases were found to have nutritional anemia while in our study 27% patients were diagnosed with nutritionalanemias.A possible reason of folate deficiency in children in Pakistan can be different inflammatory disorders of the gut, like parasitic infections,chronic diarrheas, and malabsorption states, apart from poor nutrition.AML and the rest are cases of chronic myeloid leukemia. In developing countries,there is lack of literature on  etiology, epidemiology and incidence of childhood cancer. In tropical countries, the high incidence equals the frequency of splenic enlargementdue to parasitic infections (malaria, Leishmania, brucellosis, and schistosomiasis).The frequency of visceral leishmaniasis as one of the cause of pancytopenia was found in 8% cases in our study, which is comparable to the results of Rahim et al. who showed 5.98% patients out of 424, to have visceral leishmaniasis15.

An estimated 500,000 new cases occur worldwide each year16. Typically patients of visceral leishmaniasis are malnourished with prolonged history of pyrexia, abdominal distension and cytopenias of varying severity. In endemic areas, Children are at a higher risk of developing this disease than adults. If not treatedthen, mortality rate is 90%. In our study, 7 out of 8 patients are children, like many studies that have diagnosed this disease in children17. Uncommoncauses in other studies like multiple myeloma, neuroblastoma, Myelodysplastic syndrome, malaria, and abnormal mononuclear cell infiltrate were also found rarely in our study.We found one case of each of these diseases and 2 cases of malaria, in our study in relation to pancytopenia. In our study two percent patients had malaria, 8% patients had enteric fever, 15% patients had leishmaniasis, 50% patients had megaloblastic anemia, 10% patients had aplastic anemia, 15% patients had leukemia. In India, a retrospective study done in tertiary care hospital, 21% patients of acute leukemia presented with pancytopenia. In this study out of 75%pancytopenic patients the author studied, acute leukemia was second common cause of pancytopenia after megaloblastic anemia. Gupta et al. in 2008, at Banaras Hindu University, over a period of 30 months found 25% patients of acute leukemia presenting with pancytopenia, which is comparable to our study. Also, this study revealed acute leukemia to be the second common cause of pancytopenia, as was also found in our study. In a local study in Peshawar, Rahim et al. studied 424 patients undergoing bone marrow aspiration for various hematological disorders. The frequency of acute leukemia shown by this study was 24.28%. Overall hematological malignancy was found in 27.08% patients. As in our study, Rahim et al. in 2005, out of a total of 103 24.28% patients of acute leukemia, also came across17.92% cases of ALL and 6.36% cases of AML. In our study, ALL was the most common malignancy diagnosed in 18% cases. In United States approximately 2500 cases of ALL are diagnosed per annum, accounting for almostone-third of all cases of childhood cancers. 80% percent of these are ALL, 17% are AML, and the rest are cases of chronic myeloid leukemia. Therate of ALL in our country is low in contrary to developed countries, as inChina and India. The third cause of pancytopenia common in our study is bone-marrow aplasia, comprising of 21% cases. The same results were shown by a study conducted at Jamshoro(October 2005 to March 2007).Among all patients of pancytopenia, who were under observation, 23.9% patients had aplastic anaemia while in previous studies, this proportion varies i.e. ranged 7.7 - 52.7 percent for aplastic anaemia.

Aplastic anemia is thefatal condition, if treated in appropriately or if there is delayed in diagnosis and treatment. Epidemiologically, pancytopenia shows geographical variationpattern, with high frequency in third world countries opposite to that of leukemia’s. The annual incidence of two per million cases have been presumed in Europe and Israel.In our country, due to the lack of population based studies it incidence is not known. Studies from Thailand and China showed the incidence to be about three-fold that in the West. Its exact etiology is, but many schools of thoughts agreed that it is an autoimmune disease. European studies  confirmed and categorized someof the drugs as risk factor for the development of marrow failure.Bhatnagar et al in India, as a result of his analysis of 109 patients, also revealed bone-marrow aplasia to be the third commonest cause of pancytopenia, being found in 20% patients. Environmental factors such as increased exposure to toxic chemicals and easy availability of over the counter drugsinstead of genetic factor might be involved in the development of aplastic anemia. As the land of Pakistan is more agricultural, with increased use of insecticides and pesticides; therefore the use of such medium can be an important risk factor for the development of aplastic anaemia. Hypersplenism ranked as the fourth common cause of pancytopenia in this particular study and was found in 11% patients. Ishtiaq et al in Rawalpindi came up with 19% patients of hypersplenism. The slightly lower percentage of hypersplenism in our study may be due to the fact that the underlying causes of splenomegaly, e.g. hepatitis C virus (HCV) infection, portal hypertension and cirrhosis were not determined.  While in Ishtiaq’s study portal hypertension was found in 12% patients and HCV as a cause was not ruled out.

CONCLUSION

Pancytopenia is a common problem in both settings,  clinical and hematological practice.A variety of diseases may present with pancytopenia. It is essential to recognize  the causes of pancytopenia which are common inlocal community, as few of them are entirely treatable while other can be managed to decreasethe morbidity as well as prolong the survival of patients.

Author’s Contribution:

Concept & Design of Study:

Bibi Aalia

Drafting:

Irfan Khan, Khalid Khan

Data Analysis:

Khalil Ahmad, Irfan Ullah, Muhammad Shafiq

Revisiting Critically:

Bibi Aalia, Irfan Khan

Final Approval of version:

Bibi Aalia

Conflict of Interest: The study has no conflict of interest to declare by any author.

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