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Etiological profile of pancytopenia in children: A hospital based study.

Byline: Muzamil Shabana Ejaz, Nazia Latif, Imran Rasheed Ahmed and SM Inkisar Ali


Objective: To determine the etiological profile of pancytopenia in children admitted in a Paediatric department of a tertiary care hospital.

Methodology: This is a cross-sectional study conducted at Department of Paediatrics Dow University of Health Sciences and Civil Hospital Karachi from January 2009 to December 2009. It included all the patients between 1-12 years of age, presenting with complaints of pallor, fever and bleeding manifestations and their complete blood picture showed decrease in 2 or 3 blood cells lines i.e hemoglobin less than 10g/dl, absolute neutrophil count less than 1.5X103/L and platelet count less than 150X109/L. Relevant investigations such as complete blood count, peripheral smear, reticulocyte count and bone marrow examination were done to confirm the diagnosis. The data was analyzed through SPSS version 15.0.

Results: A total of fifty patients were enrolled. There were 48% males and 52% females. Male to female ratio was 0.9:1. Mean age of patients was 7 + 3.35 years with range from 1 to 12 years. Infectious etiology was found in 50% cases followed by aplastic anemia 22%, malignancies 10% and hypersplenism 8%. Common infections found were malaria 22%, enteric fever 12% and megaloblastic anemia secondary to vitamin B12 deficiency was observed in 4% patients.

Conclusion: The most frequent etiology of pancytopenia in children was infections followed by aplastic anemia, malignancy and hypersplenism. Malaria and enteric fever were the two most commonly observed infections causing pancytopenia in children.

KEY WORDS: Pancytopenia, Etiology, Children.

How to cite this article:

Ejaz MS, Latif N, Ahmed IR, Ali SMI. Etiological profile of pancytopenia in children: A hospital based study.


Pancytopenia is one of the common clinical and hematological problems associated with various diseases in children. There is reduction in all three blood cells lines including red blood cells, leukocytes and platelets below normal values.1 Pancytopenia is usually due to decreased production of haemopoietic cells in bone marrow but it may also result from peripheral destruction of blood cells.2 Decrease in production of haemopoietic cells can occur as a result of infections, drugs, toxins or malignant cells infiltration leading to hypocellular bone marrow whereas normocellular or hypercellular marrow can be found in conditions of ineffective hematopoiesis, maturation arrest of all cells lines and peripheral sequestration of blood cells including megaloblastic anemia and hypersplenism.3 Bone marrow failure usually occur secondary to genome instability leading to cytogenic abnormalities.4 There is a wide spectrum of causes of pancytopenia in children ranging from congenital to acquired diseases.

Nutritional causes of pancytopenia are relatively more common in developing countries compared to western world. Most common causes reported in children are aplastic anemia, megaloblastic anemia, infections like malaria, enteric fever, leishmaniasis, Fanconi anemia, malignancies like acute lymphoblastic leukemia and myelodysplasia.5 Clinical presentation of pancytopenia varies from mild pallor to severe anemia, bleeding tendencies including petechiae, bruises and bleeding in the vital organs leading to life threatening emergencies.6 Early diagnosis of various causes of pancytopenia are very crucial and require prompt clinical examination and investigations like complete blood count, peripheral smear and bone marrow examination.

It is very important to determine the various etiologies of pancytopenia in order to prevent severe complications and mortality. There are few recent local studies focusing this pertinent issue in children. Therefore, the present study was done to determine the etiological profile of pancytopenia in children admitted in a paediatric department of a tertiary care hospital, this study will provide updated information and will also help paediatricians and other health professionals in early diagnosis and planning a management protocol for children presenting with pancytopenia in various diseases.


This is a cross-sectional study conducted at Pediatric Department of Dow University of Health Sciences and Civil Hospital Karachi from January to December 2009. Patients aged between 1 to 12 years, who presented with fever, pallor and bleeding manifestations and their complete blood picture showed decrease in two or three cell lines i.e. Hemoglobin level less than 10 g/dl, Absolute neutrophil counts less than 1.5X103/L and platelet count less than 150X109/ L2,13 were included in this study. Patients who were already diagnosed cases of pancytopenia and taking treatment were excluded.

A detail history of fever, bleeding manifestations like hemoptysis, epistaxis, gum bleed, heamatemesis, melena, per rectal bleed, petechiae / bruises, nutrition and history regarding drugs like chloramphenicol co-trimaxazole were taken from all the patients. Complete blood count, peripheral smear and reticulocyte count were done in all cases whereas bone marrow aspirate and trephine biopsies were done in those patients who showed persistent pancytopenia despite treating infections or peripheral smear showed blast cells. Blood and bone marrow Culture, Typhi dot, Dengue Ig M, Hepatitis serology (HBsAg, anti HCV antibodies), chromosomal breakage for Fanconi anemia and serum B 12 and RBC folate level were done in selected patients.

The data was entered and analyzed by SPSS version 15.0. Frequency and percentages were computed to present all categorical variables like gender, presence of fever, bleeding manifestations, drug intake and causes of pancytopenia. While quantitative variables like age, hemoglobin level, absolute neutrophil counts and platelet counts were presented by mean + standard deviation.


During study period, a total of fifty patients were enrolled. Out of them, 26(52%) were females and 24 (48%) were males. Male to female ratio was 0.9:1. Mean age of patients was 7 + 3.35 years with ranges from 1 to 12 years.

Regarding clinical manifestations, all patients presented with pallor, history of fever was obtained in 48 (96%), 14 (28%) presented with bleeding manifestations, poor nutritional history was elicited in 36 (72%) and history of recent drug intake was found in 8 (16%) whereas definite history of co-trimaxazole and chloramphenicol was found in two patients. Laboratory profile of fifty patients showed that hemoglobin level was less than 9g/dl in all patients, ranged from 1.7 to 9 gm/dl with mean value of 5.48 + 2.5 g/dl (mean + SD). Absolute neutrophil count (ANC) ranges from 190 to 14500/L with mean value of 2147 + 2298 and platelet count ranges from 4500 to 150000 with mean value of 71030 + 68299.

Bone marrow cellurality was assessed by bone marrow aspirate and trephine biopsy in 26 (52%) patients. Hypocellular marrow was found in 13/26(50%) patients, out of them two had Fanconi anemia suggested by chromosomal breakage, two had enteric fever also suggested by positive typhi dot and nine patients had idiopathic aplastic anemia, their serology were also negative for hepatitis B and C. Malignant infiltration was seen in four patients, out of them three had acute lymphoblastic leukemia and one patient had acute myeloid leukemia. In three patients bone marrow showed megakaryocytes consistent with Idiopathic thrombocytopenia, one of them had autoimmune hemolytic anemia consistent with Evan syndrome.

Megaloblastc changes, on bone marrow examination were observed in two cases, their serum B 12 level was also found to be low. Bone marrow was found to be normocelllar in four patients, out of them one had Hodgkins lymphoma diagnosed on lymph node biopsy and other three had infectious etiology.

In this study infection was the most frequent etiology of pancytopenia. Common infections observed were malaria in eleven patients, enteric fever six, sepsis four, dengue and hepatitis B in two patients each. Regarding malaria, nine had plasmodium falciparam, one had both plasmodium falciparum and vivax and one had isolated plasmodium vivax malaria. Out of six patients of enteric fever, one had positive blood culture for Salmonella typhi, two were diagnosed on bone marrow and four had positive typhidot test. Four (8%) malnourished patients presented with sepsis, two had positive blood cultures showing staphylococcus aureus and klebsiella pneumoniae each. Two (4%) patients had Dengue fever suggested by Dengue IgM.

Aplastic anemia was another frequent cause of pancytopenia presented in twenty-two cases. Out of which nine were idiopathic and two had Fanconi anemia. Malignancy was found in five patients. Other causes of pancytopenia included megaloblastic anemia secondary to vitamin B12 deficiency 2 (4%), hypersplenism 4 (8%) and idiopathic thrombocytopenia in 3 (6%), cases (Table-I).


Pancytopenia is a frequent hematological problem occurring in children. There is wide range of etiologies of pancytopenia in children and it is found in all age groups. In our study mean age of presentation was seven years; females were more affected then males. Children with pancytopenia usually presents with fever, pallor and bleeding manifestations including hematemesis, melena, epistaxis and bruises. A local study showed that fever and bleeding from various sites was present in 70% patients whereas anemia was present in 100% cases.7 Our study also showed that pallor was present in all the cases whereas fever was present in 96% cases and bleeding manifestations were found in 28% cases.

Table-I: Etiology of pancytopenia (n=50).



Aplastic anemia###11###22%





Nutritional Deficiency###2###4%

Pancytopenia may result from intake of many drugs including co-trimaxazole, chloramphenicol and antimalarial drugs containing sulphonamide group. History of drug intake however is not obtained in many cases because of non availability of the prescriptions of the doctors or due to intake of locally prepared medicines given by the general physicians from their dispensaries. In a study history of recent drug intake was obtained in only 12% patients8 whereas in the present study it was found in 16% patients and definite history of co-trimaxazole and chloramphenicol was present in two patients only.

Bone marrow examination is one of the most frequently used diagnostic procedures for evaluation of unexplained pancytopenia.9 In the present study bone marrow was done in twenty six patients and it was hypocellular in fifty percent cases. Infections were the most frequent etiology of pancytopenia in our study, found in 50% cases, majority of children presented with malaria 22% followed by enteric fever 12%, Sepsis 8%, Hepatitis B and Dengue fever 4% each. Other studies also showed similar results. In a study infection was the main cause of pancytopenia in children 64% including viral infections 24%, sepsis 17% and malaria.10 Another study from Pakistan showed that enteric fever, malaria and sepsis were the common infectious diseases leading to pancytopenia.11

Data from India is variable, a study showed infections as one of the frequent causes of pancytopenia in children 21%, among these, enteric fever was found in 30% patients followed by malaria, kalazar and bacterial infections12 whereas another study showed infections as a third most important cause of pancytopenia, leishmaniasis was the commonest infection found while malaria and enteric fever were less frequently reported.13

Aplastic anemia is a haemopoietic stem-cell disorder resulting in pancytopenia and hypocelllular bone marrow. Most cases are usually acquired and have immune mediated pathophysiology.14 In our study aplastic anemia was the second most frequent etiology of pancytopenia 22%, there were two cases of Fanconi anemia and nine cases of idiopathic aplastic anemia. Another study from India also showed aplastic anemia as a frequent cause of pancytopenia in children.12 A local study reported only three cases of inherited Fanconi anemia.8

Childhood hematological malignancies including acute lymphoblastic leukaemia and acute myeloid leukaemia are preceded by a period of apparent bone marrow failure.15 A study done in Pakistan showed that aleukaemic leukaemia was present in 19%16 whereas another study showed acute lymphoblastic leukaemia in 4.8% and acute myeloid leukaemia in 3.8% cases.3 In our study malignancies were the third commonest cause of pancytopenia found in 10% cases.

Nutritional anemia, megaloblastic anemia is one of the leading causes of pancytopenia in developing countries. The underlying cause of megaloblastic anemia in children is vitamin B12 and folate deficiency.

Diagnosis of megaloblastic anemia is very important as it is a treatable as well as preventable cause of pancytopenia. In countries like Pakistan and India, poor nutritional intake of animal proteins leads to deficiency of vitamin B12 in children whereas chronic diarrhea and malabsorption syndromes are other causes for folate and vitamin B12 deficiencies apart from poor nutrition. In many local studies megalablastic anemia was the commonest cause of pancytopenia in children. 3,8,16 In one of the study it constituted the largest group of pancytopenia found in 39% cases.17 Reports from India also showed comparable results.18,19 In our study it was less frequently reported.

Hypersplenism is another common cause of decrease cellular counts in children. It is associated with haemoglobinopathies like thalassemia, sickle cell anemia and chronic liver diseases. In present study hypersplenism was found in 8% patients out of whom three had thalassemia major and one had sickle cell anemia.

Another local study showed that hypersplenism was the second most common cause of pancytopenia found in 12% patient7 whereas in a study done in India it was present in 11% cases.20 In our study idiopathic thrombocytopenia and Evan syndrome were found as underlying cause of pancytopenia in two and one cases respectively.

Another study also showed similar results.10 Hence pancytopenia is a common problem in paediatric population associated with severe morbidity and mortality, timely diagnosis of its causes and planning management accordingly can prevent severe complications.

Limitations of the study: This is a hospital based study done on a small sample size therefore results cannot be generalized for whole paediatric population.


The most common etiology of pancytopenia was infections in children followed by aplastic anemia, malignancies and hypersplenism. Malaria and enteric fever were the most frequent infectious diseases leading to pancytopenia in children.

Recommendation: More studies in paediatric population for evaluation of pancytopenia should be done to make appropriate guidelines for diagnosis and management of pancytopenia in children.


We are thankful to doctors of Paediatric Department for their support during conduction of the study and Mr. Furqan Baig for secretarial assistance.


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1. Dr. Muzamil Shabana Ejaz, Assistant Professor, Dept. of Paediatrics, Dow University of Health Sciences and Civil Hospital Karachi.

2. Dr. Nazia Latif, Registrar, Department of Paediatrics, Civil Hospital Karachi.

3. Dr. Imran Rasheed Ahmed, Assistant Professor, Department of Paediatrics, Dow University of Health Sciences and Dow International Medical College Karachi.

4. Prof. S.M. Inkisar Ali, Professor, Department of Paediatrics, Dow University of Health Sciences, Karachi. Correspondence: Dr. Muzamil Shabana Ejaz, E-mail:

Received for Publication: June 4, 2010

Revision Received: January 18, 2011

Revision Accepted: February 15, 2011

Authors Contribution:

1. M.S.E., Study conception, designing, Collection and statistical analysis of data, writing and editing of manuscript.

2. N.L, Collection of data, Statistical analysis of results and collection of references.

3. I.R.A, Study Designing, collection of references and critical review of manuscript.

4. S.M.I.A., Reviewing and final approval of the manuscript.

Muzamil Shabana Ejaz, Nazia Latif, Imran Rasheed Ahmed, SM Inkisar Ali
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Author:Ejaz, Muzamil Shabana; Latif, Nazia; Ahmed, Imran Rasheed; Ali, SM Inkisar
Publication:Pakistan Journal of Medical Sciences
Article Type:Report
Geographic Code:9PAKI
Date:Jun 30, 2011
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