Etiological Evaluation of Pancytopenia in A Tertiary Care Hospital

Background: Pancytopenia is not a disease by itself, however it is a common hematological problem characterized by simultaneous presence of anemia, leucopenia and thrombocytopenia. The disease pattern associated with pancytopenia varies with geographic location, age group, nutritional status, drug intake and prevalence of infective disorder. This prospective study was to investigate and identify different causes of pancytopenia with frequency, to ascertain percentage of occurrence of pancytopenia, to determine its incidence in relation to sex and age, and to compare findings with those of other similar studies. Methods: 80 patients diagnosed with pancytopenia were clinically evaluated, with complete blood count, peripheral smears, and bone marrow aspiration-biopsy whenever possible in Justice K. S. Hegde Hospital attached to Nitte University, Deralakatte, Mangalore, from June 2012 to June 2014. Results: Among the 80 cases analyzed, most of the cases were seen in the age group of 41-50 years, with male predominance. Hypersplenism (28.75%), malaria (16.25%) and megaloblastic anemia (13.75%) were the three commonest causes in our hospital. In 13 cases of malaria, Plasmodium vivax (8 cases) was most commonly noted. Conclusion: The present study concludes that varied causes of pancytopenia can be attributed to the geographic area, nutritional and drug intakes, personal habits, infective causes, stringency of diagnostic criteria, and differences in methodology used. Hence, a detailed clinical history and meticulous examination along with hematological investigations provide invaluable information in the complete workup of patients with pancytopenia for understanding the disease processes, planning further investigations and management, and ascertain the cause. Original Article *Corresponding author: Dr. Anuja Dasgupta, Dept. Pathology, K.S Hegde Medical Academy, NITTE University, Deralakatte, Mangalore -575018, India Phone: +91 9902336642 Email: [email protected] A-442 Evaluation of Pancytopenia Annals of Pathology and Laboratory Medicine, Vol. 03, No. 05, (Suppl) 2016 Introduction Pancytopenia is defined as reduction of the cellular elements of blood with hemoglobin <10gm/dl, white blood cell count <4000/mm3 and platelet count <100,000/mm3. Hence, is not a disease entity but rather a triad of findings that may result from a number of disease processes.[1,2] The etiology of pancytopenia varies in different populations depending on the age, nutritional status, geographic location and the prevalence of infections. Some causes of pancytopenia with prompt diagnosis are curable. However, in certain circumstances where complete cure is not possible, early diagnosis and supportive treatment can improve the quality of life by decreasing morbidity and mortality.[3,4] The present study was carried out in patients diagnosed with pancytopenia attending to our hospital in order to find the incidence of various etiological factors with clinical details, hematological findings and bone marrow (BM) aspiration-biopsy whenever possible. Materials and Methods This prospective study was carried out over a period of two years, June 2012 to June 2014 in the Clinical Diagnostic Laboratory, Justice K. S. Hegde Charitable Hospital, NITTE University, Deralakatte, Mangalore. Approval from institutional ethical committee of K. S. Hegde Medical Academy (KSHMA) was obtained to conduct this study. The institutional ethical committee felt an informed consent was not required to conduct this study and thus deemed it to be not applicable. Criteria for inclusion: i. All age groups and both sexes ii. Hemoglobin: <10g/dL iii. Total leukocyte count: <4000/μL, and iv. Platelet Count: <100,000/μL. Relevant history was taken in every patient including their habits and intake of drugs, along with meticulous clinical examination. In all patients, complete blood count and peripheral smear study, and BM study wherever possible. Other investigations which whenever indicated included: chest and bone radiographs, ultrasound / C.T. Scan, urine and stool examination, liver function test, urinary Bence Jones proteins and serum electrophoresis, serological investigations and ELISA tests, and tests for serum ferritin, cobalamin, folic acid, lactate dehydrogenase and antinuclear antibody. A clinico-pathological correlation was done in all cases before reaching a definitive diagnosis and the findings of this study was compared with similar other studies. Result A total of 80 patients were studied with a male to female ratio of 1.2:1. The age ranged from 2-90 years, with the maximum number of cases observed in the 41-50 years age group followed by 31-40 years (Fig 1). The causes of pancytopenia with age distribution of the patients are shown in Table 1. Hypersplenism was observed in 23 (28.75%) cases constituting 14 males and 9 females. Hypersplenism was due to alcohol liver disease (ALD) (12 of 23 cases), and chronic liver disease (CLD) of idiopathic type (8 cases) and other causes (3 cases). ALD was most encountered in males between 31-70 years although one case was noted in a 42 year old woman. CLD was mostly noted in women of age group 41-50 years. The other three cases included: portal vein thrombosis with cavernous transformation, compensated portal hypertension caused by multiple liver metastasis from carcinoma rectum and Hodgkins lymphoma. Of the thirteen (16.25%) cases of malarial infestation with an age range of 5-50 years, Plasmodium vivax was the predominant parasite seen in 8 cases, mixed malarial infestation (Plasmodium vivax and Plasmodium falciparum) in 4 cases and 1 case of Plasmodium falciparum infestation (Fig 2). Megaloblastic anemia (MA) was seen in 11 (13.75%) cases with the commonest age groups being between 31-50 years (54.55%) and 61-80 years (45.45%). Females were affected more than males. BM examination was performed in 6 cases and showed hypercellular marrow with megaloblastic features and giant metamyelocytes (Fig 3). There were 2 cases with history of alcohol consumption. We encountered seven (8.75%) cases of acute leukemia (AL) which included 4 children and 3 adults. Among the children, 3 developed Acute Lymphoblastic Leukemia (ALL) with monotonous population of lymphoblasts and 1 had Acute Myeloid Leukemia (AML) (M2). In the adults, all were diagnosed with AML (M2, M3, M4). The case with AML (M4) had increased number of monoblasts (Fig 4). In our study we observed six (7.5%) cases of pancytopenia following intake of drugs over a long duration of time or as a transient presentation and if when discontinued the blood counts would either come to normal range or remained in low counts. There were two cases of anti-platelet drug intake, clopidogrel which was administered to patients with Ischemic Heart Disease and Non ST elevation Myocardial Infarction. Other cases constituted two cases of chemotherapy-induced, one case of anti-rheumatic drug leflunamide which lead to myelofibrosis grade 2 and a case of Break Bone Fever by Chickungunya virus with four years of selfadministered analgesic Indomethicin. Dasgupta et al. A-443 www.pacificejournals.com/apalm eISSN: 2349-6983; pISSN: 2394-6466 We noted two (2.5%) alcoholic male patients of ages 48 years and 70 years. Both were on heavy alcohol consumption for over 20 years. Ultrasound of both showed features of liver cirrhosis without splenomegaly. The other causes of pancytopenia included in our study were three (3.75%) cases each of multiple myeloma, aplasitc anemia (AA) and myelodysplastic syndrome (MDS) of Refractory Anemia with Excessive Blasts (RAEB) type; two (2.5%) cases of dengue fever and one (1.25%) case each of myelofibrosis, iron deficiency anemia (IDA), lymphoma (lymphoplasmacytic), HIV infection, systemic lupus erythematous (SLE), multi-focal bone metastasis from adenocarcinoma of prostate, and secondary to autoimmune cause. Discussion The present study with a total of 80 patients of pancytopenia was conducted to analyze the incidence of various causes of pancytopenia, age pattern, gender-wise along with their clinical findings, hematological and BM spectrum. The statistical data hence obtained were compared with previous published literature. The age of the patients ranged 2 90 years with the commonest age group being 41 50 years (Table 2). Majority of the cases presented in 4th and 5th decade (Fig 1). Few other studies too have reported 4th and 5th decade as the commonest age group for presentation of pancytopenia.[5,6,7,8] A male predominance was noted in our study which was similar to other studies. With social taboos in our society, this could make health care facilities more readily available to males in comparison to females therefore showing an increased in male presentation at hospitals. The commonest cause of pancytopenia, reported in various studies throughout mostly in the subcontinent area had been MA.[9] This is in sharp contrast with the results of our study, where the commonest cause of pancytopenia was found to be hypersplenism (n = 23, 28.75%). In other similar studies the incidence varies from 3 to 68%.[5] This contrast could suggest that there is an increasing trend of alcoholism in today’s society; hence most patients attending to our hospital present with ALD, and hypersplenism being one of the consequences. Table :. Age distribution of the patients and causes of pancytopenia. Causes Age group (in years) Total 2-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 Hypersplenism 1 7 6 2 6 1 23 Malaria 1 4 4 2 2 13 Megaloblastic anemia 3 3 2 3 11 Acute leukemia 3 2 1 1 7 Drug induced 2 3 1 6 Multiple myeloma 2 1 3 Aplastic anemia 1 2 3 MDS 1 1 1 3