Pancytopenia: A clinico-hematological study
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0975-2870.122763
Background: A review of both Western and Indian literature shows that there are few comprehensive studies on pancytopenia. In India, the causes of pancytopenia are not well defined. This data, if available, would help in planning the diagnostic and therapeutic approach in patients with pancytopenia. Aim: To evaluate the cases of pancytopenia by peripheral smear and/or bone marrow aspiration and/or bone marrow biopsy to find out the etiology, clinical, hematological, and histomorphologic features of pancytopenia. Materials and Methods: Detailed hematological investigations a complete hemogram, peripheral smear examination, bone marrow aspiration, and biopsy examination were done. Results: The most common cause of pancytopenia in our study was megaloblastic anemia (56%), followed by hypoplastic/aplastic anemia (14%), hypersplenism (8%) and post viral illness (6%). Conclusion: Megaloblastic anemia due to vitamin B12/folate deficiency seems to reflect the higher prevalence of pancytopenia in Indian subjects, putting hypoplastic/aplastic anemia in the second position, which is the leading cause for pancytopenia in the Western countries. Keywords: Aplastic anemia, megaloblastic anemia, pancytopenia
Pancytopenia was not a discrete hematological entity till as late as 1919. The term was used almost synonymously for aplastic anemia, it being the major cause of pancytopenia in Western countries. [1],[2] Pancytopenia is reduction in all three major elements of blood formed, i.e, erythrocytes, leukocytes, and platelets. [3] It is not a disease entity but a triad of findings that may result through different mechanisms like destruction of marrow tissue by toxins, radiation (aplastic or hypoplastic marrow), replacement by abnormal or malignant tissue like Hodgkin's and non-Hodgkin's lymphoma, multiple myeloma, myelofibrosis, or suppression of normal marrow growth and differentiation like megaloblastic anemia and systemic lupus erythematosus. [1],[3] It has been observed in the Indian scenario that megaloblastosis (vitamin B12 and/or folate deficiency) is the commonest cause of pancytopenia. [4],[5],[6] Other important conditions manifesting as pancytopenia are aplastic/hypoplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH), overwhelming infections, hypersplenism, etc. [1] The present study was carried out to evaluate the cases of pancytopenia by peripheral smear and/or bone marrow aspiration and/or bone marrow biopsy and to find out the etiology of pancytopenia along with clinical, hematological, and histomorphologic features.
To evaluate the cases of pancytopenia and to ascertain their causes, this prospective study was carried out in the Department of Pathology, Bharati Vidyapeeth Deemed University Medical College, Pune, Maharashtra, over a period of 2 years, from September 2010 to September 2012. All the patients referred to hematology section of the pathology department for routine hematological investigations and peripheral smear (PS) examination were screened for pancytopenia, and a total of 50 cases were selected based on the following three criteria - hemoglobin (Hb) less than 9 gm/dl, total leukocyte count (TLC) less than 4000/mm 3 , and platelet count less than 140,000/mm 3 . [7] Complete medical history and clinical details were obtained for each patient. Detailed hematological investigations were done in the blood samples. Measurement of Hb, mean corpuscular volume (MCV), TLC, differential leukocyte count (DLC), and platelet count was done on Sysmex KX-21 and also cross-checked by peripheral blood smear examination for which Leishman stain was used. Peripheral smear examination was done systematically under low, high, and oil immersion for RBC morphology - i.e. anisocytosis, poikilocytosis, chromia, polychromasia, nucleated red blood cells, and presence of inclusions. Rouleaux formation, if present, was noted. Anemias were then classified morphologically into four groups - normocytic normochromic, microcytic hypochromic, macrocytic, and dimorphic. Differential WBC count was done with a special note of defective granulation in neutrophils and hypo/hypersegmentation in neutrophils, and platelet count and morphology was analyzed. Also, presence of any parasites was tested for. Informed consent was taken for bone marrow studies. Bone marrow aspiration was done from posterior superior iliac spine using Salah bone marrow aspiration needle. Simultaneously, from the same puncture site but from a different plane, bone marrow biopsy was done using Jamshidi-Swaim needle, taking all aseptic precautions.
The most common cause of pancytopenia in our study was megaloblastic anemia (56%) [Figure 1] and [Figure 2], followed by hypoplastic/aplastic anemia (14%) [Figure 3]. Other causes included hypersplenism (8%), post viral illness (6%), sepsis (4%), malaria (4%), post typhoid fever (2%), myelodysplastic syndrome (2%), myelofibrosis (2%), and miscellaneous (2%) [Table 1].
Three cases of megaloblastic anemia had concurrent iron deficiency as well. Post viral illness cases comprised two cases of dengue and one case of H 1 N 1 swine flu. The age range of patients in our study was from 8 to 69 years. The commonest age group for presentation of pancytopenia was between 21 and 30 years, with a total of 16 (32%) cases belonging to this group. This was followed by 11-20 years (20%), 31-40 years (18%), and 41-50 years (10%) [Table 2].
Out of the 50 cases, 31 were males and 19 were females. Slight male preponderance was seen. The overall male to female ratio was 1.63:1. Male to female ratio was found to be the same in 1-30 years age group. Clinical features in various causes of pancytopenia Patients with pancytopenia presented with a variety of different clinical features, but some common features were identified. Progressive pallor was the most common clinical feature and it was found in almost every case. Generalized weakness, fever with or without chills, and dyspnea were the other common presenting features. Bleeding manifestations like epistaxis, gum bleeding, and petechial rash were common in the hypoplastic/aplastic anemia group. Hepatomegaly (14%) and splenomegaly (22%) were the other common clinical findings. Peripheral blood findings Anisocytosis of varying severity was the commonest morphologic type (58%) followed by normocytic normochromic (34%) and dimorphic picture (8%) in the decreasing order of frequency. Normocytic normochromic anemia was the common finding in all other causes of pancytopenia except for megaloblastic anemia and myelofibrosis where anisocytosis was common. In myelofibrosis, peripheral blood smear was showing characteristic tear drop red cells. Hypersegmented polymorphs were the commonest peripheral blood finding in megaloblastic anemia. Hb level distribution in various causes of pancytopenia The Hb levels of patients in our study ranged from 2 to 9 g/dl. Of the 50 cases, 19 cases (38%) had Hb levels between 3 and 5 g/dl, suggesting severe degree of anemia at the time of presentation as pancytopenia. Hb levels were more severely reduced in the hypoplastic/aplastic anemia group. Platelet count distribution in various cases of pancytopenia The platelet counts of patients in our study ranged from 10,000/mm 3 to 1.26 lakh/mm 3 . Majority, i.e. 23 cases (46%), had platelet counts between 50,000/mm 3 and 1 lakh/mm 3 . Also, 8% of the patients had platelet counts below 20,000/mm 3 and all these patients were from hypoplastic/aplastic anemia group. Distribution of megaloblastosis Out of 28 cases, 25 cases (89%) showed pure megaloblastic anemia of varying severity whereas 3 cases (11%) showed dimorphic anemia, i.e. a combination of iron deficiency and megaloblastic anemia, in varying proportions [Table 3].
Though pancytopenia is not a disease by itself, it is a striking feature of many serious and life-threatening illnesses and is caused by various different disorders. [1],[7] Extensive studies have been conducted for the different etiological factors of pancytopenia like megaloblastic anemia, aplastic anemia, leukemia, myelodysplastic syndrome, etc. However, there are a limited number of comprehensive studies on this subject. [6] In India, the causes of pancytopenia are not well defined. This data, if available,would help in planning the diagnostic and therapeutic approach in patients with pancytopenia. Keeping this in mind, the present study of pancytopenia was carried out mainly with the twin aims of diagnosing the patients of pancytopenia and finding out the common disease entities responsible for it. [6],[7] Comparison of the common causes of pancytopenia reported from various studies conducted in the Indian subcontinent with those of the present study is presented in [Table 4]. [4],[5],[6],[7],[8] The commonest cause for pancytopenia in our study was megaloblastic anemia, which is consistent with that reported by Tilak et al. and Khodke et al. in their study of 77 and 50 cases of pancytopenia, respectively. [4],[6] This was followed by aplastic anemia which is the commonest cause in the studies of Kumar et al. and Niazi et al. [7],[8] The age range in our study was from 8 to 69 years. The maximum number, i.e. 39 cases (78%), of patients were below the age of 40 years with the majority, i.e. 26 cases (52%), in their second and third decades and the commonest age group for presentation being between 21 and 30 years [Table 2]
A slight male preponderance was seen. The overall male to female ratio was 1.63:1. However, the male to female ratio was equal in the 1-30 years age group. Other studies also reported male preponderance. Tilak et al. studied 77 cases of pancytopenia and encountered maximum number of cases under the age of 20 years (32.47%) with male to female ratio being 1.13:1. [6] Similarly, Khodke et al. studied 50 cases of pancytopenia and found maximum number of cases in the age group of 12-30 years (44%) with male to female ratio being 1.3:1. [4] Niazi et al. have also reported the commonest age group between 21 and 30 years of age with male to female ratio being 1.7:1 in their study of 89 cases of pancytopenia. [8] After analyzing our data, we feel that the presenting symptoms in pancytopenic patients are usually attributable to anemia or thrombocytopenia, with leukopenia being an uncommon cause of the initial presentation but can become the most serious threat to life during the subsequent course of the disorder, adding up to the morbidity and mortality as has been suggested by deGruchy. [1] Thus, we suggest that in a patient of anemia or prolonged illness, appearance of pyrexia and/or bleeding manifestations should put the physicians on high alert, as there are very high chances of the patient landing up in pancytopenia, in which case further investigations should be carried out to look for the possible cause. Since severity of pancytopenia and the underlying pathology determines the management and prognosis of these patients, treatment should commence at the earliest possible to prevent the unacceptable serious complications of pancytopenia. If all the elements of the complete blood cell count are considered in the clinical context, including the findings of physical examination, they can provide invaluable information guiding to the possible causes for pancytopenia and helping in planning the workup of tests needed for definite diagnosis.
With the help of detailed clinical history, physical examination, and hematological investigations, pancytopenia can be diagnosed and the causes can be ascertained. Megaloblastic anemia due to vitamin B12/folate deficiency seems to reflect the higher prevalence of pancytopenia in Indian subjects, putting hypoplastic/aplastic anemia in the second position, which is the leading cause for pancytopenia in the Western countries. Pancytopenia due to megaloblastic anemia is albeit transient and easily reversible with appropriate treatment. Thus, megaloblastic anemia should always be considered in the evaluation of pancytopenia in Indian settings. However, other important causes of pancytopenia should be kept in mind while planning investigations for the complete workup of pancytopenic patients. Early treatment can be planned depending upon the cause and severity of pancytopenia. In our study, majority of the cases had a treatable cause and so carried better prognosis.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Similar in PUBMED |
 Search Pubmed for |
| Search in Google Scholar for |
| Related articles |
| Access Statistics |
| Email Alert * |
| Add to My List * |
| * Registration required (free) |
| In this article |
| Abstract |
| Introduction |
| Materials and Me... |
| Results |
| Discussion |
| Conclusion |
| References |
| Article Figures |
| Article Tables |
| Article Access Statistics | |
| Viewed | 10503 |
| Printed | 128 |
| Emailed | 3 |
| PDF Downloaded | 991 |
| Comments | [Add] |
| Cited by others | 4 |
