Comparison of the severity of cytopenias with etiologic factors in patients with pancytopenia and bicytopenia

Introduction The aim of this study was to evaluate the severity of hematological findings according to etiology in patients with pancytopenia and bicytopenia. Methods Patients with bicytopenia and pancytopenia who were examined in Diyarbakir Children Hospital Pediatric Hematology and Oncology clinic between June 2017-June 2018 were evaluated retrospectively. Results Of the 130 patients included in the study, 73 (56.2%) were male and 43 (43.8%) were female. The mean age of the patients was 4.9 ± 4.86. Forty-five (34.6%) patients had pancytopenia and 85 (65.3%) had bicytopenia. The youngest patient was 1-month old and the oldest patient was 18-year-old. The mean blood count parameters were white blood cell (WBC): 10.207 ± 39.781, neutrophil: 1515 ± 1418, hgb: 9.3 ± 2.3, mean corpuscular volume (MCV): 80 ± 13.1, platelet: 118.823 ± 93.645. Three out of 130 patients had hyperleukocytosis (WBC > 50.000/mm3). Vitamin B12 deficiency was detected in 35 patients. When patients with primary hematological disease were compared with patients with secondary causes of cytopenias, a significant difference was found in terms of leukocyte count, hemoglobin level, MCV elevation, and low platelet count. Conclusion The determination of the severity of cytopenias in differential diagnosis may be useful in distinguishing primary hematological diseases from secondary causes of pancytopenia and bicytopenia. However, vitamin B12 deficiency in developing countries is one of the most important causes of public health as well as in the etiology of pancytopenia and bicytopenia.


Introduction
Pancytopenia or bicytopenia is a condition characterized by the decrease of cellular elements in two or three series which develop in childhood due to different etiological reasons. A wide range of causes can be detected in the etiology ranging from transient suppression to malignancies, nutritional deficiencies to inflammatory diseases [1].

Discussion
Pancytopenia and bicytopenia is a life-threatening condition in terms of both the underlying cause and the consequences of childhood.
Although there may be transient cytopenias due to infections in the etiology, serious diseases related to bone marrow can also be seen.
Determining the cause of cytopenia is particularly important for the patient's follow-up and treatment. When the literature is examined, differences in age and geographic regions are observed in etiology of pancytopenia and bicytopenia patients [5]. In a study of 134 patients in Zimbabwe, the most common cause was megaloblastic anemia, followed by aplastic anemia and acute leukemia [6]. In France, Imbert et al. [7] reported the most common cause of myeloid leukemias (42%) in 213 adult patients. In a study involving adult and pediatric patients in Nepal, the most common cause was hypoplastic bone marrow in children (38.1%) and megaloblastic anemia in adults (30.2%) [8]. The most common cause of megaloblastic anemia was found in one of the studies in Pakistan [9]. In my study, infections were the most common cause of pancytopenia and bicytopenia.
Cytopenias secondary to infection were followed by vitamin B12 Megaloblastic anemia was detected in only 3.5% of the patients [12].
Unlike my study, I associated this difference in the frequency of B12 deficiency with the development of capital Ankara. Bhatnagar et al. [13] reported that 109 children with pancytopenia were diagnosed with megaloblastic anemia and acute leukemias, followed by infections in 3 rd place. In a study performed in 105 pancytopenic children, infections were the third most common cause. The most common cause of infection was Kala-Azar [14]. In my study, the most common cause of infection was Epstein-Barr Virus (EBV) infection. In contrast to the study of Gupta et al. [14], Kala-Azar was not detected in any patient. Other infectious causes other than EBV were brucellosis, nonspecific upper and lower respiratory tract infections, and gastroenteritis. The reason for not detecting Kala-Azar infection was considered as the primary concern of the department of infectious diseases and the preventions taken by the ministry of health. EBV infections are usually characterized by fever, exudative pharyngitis, lymphadenopathy and hepatosplenomegaly. These findings are especially important in the differential diagnosis with hematological malignancies. Thrombocytopenia, hemolytic anemia, agranulocytosis and hemophagocytic lymphohistiocytosis are among the hematologic complications seen in EBV infections [15,16]. Cytopenias can develop especially in acute phase during viral infections due to cytokine release, drug side effects, decreased production because of bone marrow suppression, or hemolysis. The biggest difference of cytopenias due to viral infections to hematological malignancies and bone marrow pathologies is that the degree of cytopenia is milder [18]. EBV infection was detected in 12 (7%) patients in my study. It was observed that the degree of cytopenia of these patients was milder than group 1. Acute leukemias and bone marrow disorders are important causes of pancytopeniabicytopenia in children. Acute leukemias may be presented with leukocytosis and may also be associated with pancytopenia and bicytopenia. The incidence of severe cytopenia which requires transfusion support in bone marrow pathologies is high [19]. In one study, it was found that macrocytosis was more common in bone marrow-derived pathologies and therefore an important finding [20].
In my study, a significant difference was found between the patients who were thought to have primary hematological disease and the patients who were related to the secondary causes of cytopenias.

Conclusion
In conclusion, determination of the severity of cytopenias may be useful in differentiating primary hematological diseases from cytopenias due to secondary causes and without further examinations in the differential diagnosis. In addition to this, vitamin B12 deficiency should be the first to be considered in the etiology of pancytopenia and bicytopenia especially in developing countries. Vitamin B12 deficiency is so common in public health.
What is known about this topic • Pancytopenia and bicytopenia is a life-threatening condition in terms of both the underlying cause and the consequences of childhood; • A wide range of causes can be detected in the etiology ranging from transient suppression to malignancies, nutritional deficiencies to inflammatory diseases; • Differences in age and geographic regions are observed in etiology of pancytopenia and bicytopenia patients.

What this study adds
• Severity of cytopenias may be useful in differentiating primary hematological diseases from cytopenias due to secondary causes and without further examinations; • Vitamin B12 deficiency should be the first to be considered in the etiology of pancytopenia and bicytopenia in developing countries.

Competing interests
The author declares no competing interests.

Authors' contributions
The author has read and agreed to the final manuscript.