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Study of Megakaryocytes in Bone Marrow Aspiration Smears in Patients with Thrombocytopenia Choudhary PK1, Sing SK1, Basnet R B1

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Study of Megakaryocytes in Bone Marrow Aspiration Smears in Patients with Thrombocytopenia Choudhary PK1, Sing SK1, Basnet R B1 Journal of Pathology of Nepal (2013) Vol. 3, 476 -481 cal Patholo Journal of lini gis f C t o o f N n e io p t a a l i - c 2 o 0 s 1 s 0 PATHOLOGY A N u e d p a n of Nepal l a M m e h d t i a c K al , A ad ss o oc n R www.acpnepal.com iatio bitio n Building Exhi Original Article Study of megakaryocytes in bone marrow aspiration smears in patients with thrombocytopenia Choudhary PK1, Sing SK1, Basnet R B1 1Department of Pathology, National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal ABSTRACT Keywords: Background: Dysplastic changes in megakaryocyte are well-recognized features of myelodysplastic Megakaryocytes; syndrome. However, several studies have shown it’s occurrence in various other disorders. This study Thrombocytopenia; was done to understand the various megakaryocytic alterations including the dysplastic forms in Myelodysplastic syndrome hematological disorders presenting with thrombocytopenia other than in myelodysplastic syndrome. Materials and Methods: All cases of thrombocytopenia in the study period of May 2010 to April 2012 were included. Bone marrow aspiration study was done in each case of thrombocytopenia. Megakaryocytes were examined in bone marrow aspiration smears in terms of their number and morphology. Dysplasia was considered significant if ≥ 10% of megakaryocyte examined show dysplastic morphology. Results: Dysplastic megakaryocytes were observed in 52.3%, 50% and 21.2% of the cases of megaloblastic anemia, acute leukemia and immune thrombocytopenic purpura respectively. Most common dysplastic feature observed were multiple separate nuclei (25.2%) and micromegakaryocyte (17.3%). Hypogranular form was the least observed dysplastic feature (1.4%; 2/139 cases). Conclusion: Dysplasia in megakaryocyte is a quiet common occurrence in various non-myelodysplastic syndroms related thrombocytopenia. The mere presence of dysplastic megakaryocyte should not prompt an interpretation of myelodysplastic syndroms and should always be correlated with patient’s clinical and other hematological parameters. INTRODUCTION Thrombocytopenia is a very common hematological or be associated with bicytopenia or pancytopenia.1 presentation for which a bone marrow aspiration is often Immune thrombocytopenic purpura (ITP) is a very common sought. It has been defined as platelet count less than 150,000/ cause of thrombocytoepenia. Various other haematological mm3.1 Patients usually present with features of superficial conditions such as megaloblastic anemia, aplastic anemia bleeding including petechiae, echymosis, epistaxis and and leukemias can also present with thrombocytopenia. gum/vaginal bleeding. Thrombocytopenia can be isolated Since a number of different artifacts can produce Correspondence: pseudo-thrombocytopenia, peripheral blood smear Dr. Prabesh Kr. Choudhary, MD examination is often the initial step in evaluation to look Department of Pathology, Nobel Medical College, Biratnagar, Nepal for features of pseudo-thrombocytopenia such as platelet 2 Email: [email protected] clumping, satellitism and phagocytosis by neutrophils. Normal maturation and platelet formation results from Study of megakaryocytes in thrombocytopenia 477 megakaryocytic deoxyribonucleic acid (DNA) replication platelet count was performed and and Giemsa stained fresh that occurs without cell division resulting in large lobulated, capillary blood films were prepared for every case to look polypoid nucleus.1 A wide variety of growth factors like for evidence of pseudo-thrombocytpenia such as platelet thrombopoietin act synergistically with other hematopoietic agglutination, satelletosis and phagocytosis by other cell.2 cytokines and transcriptional factors including HOX factors, Cases showing evidence of psedo-thrombocytopenia or AML-1 and NJ-1 which stimulate the maturation and receiving chemo- or radiotherapy were excluded from the growth of megakaryocytes.1 Defect in any of these stages of study. Under all aseptic measures, bone marrow aspiration megakaryocytopoiesis can lead to dysmegakaryocytopoiesis was then performed for every case as per standard and thrombocytopenia. methodology.4 The bone marrow aspiration smears were then stained with Giemsa stain.4 Dysmegakaryocytopoiesis is characterized by various megakaryocytic alterations in bone marrow aspirates The bone marrow smears were examined as per the standard and include both dysplastic and non-dysplastic features. guideline and the findings were documented. Number of Dysplastic features of megakaryocytes are multiple megakaryocyte was expressed as the number per 10 low separated nuclei, micromegakaryocytes (size of large power fields (LPFs) and were further subdivided in to lymphocyte/monocyte with single or bilobed nucleus) and absent (0/10 LPFs), decreased (1/5-10LPFs), normal (1/1-3 hypogranular forms (megakaryocyte with pale grey or LPFs) and increased (>2/LPF).3 At least 30 megakaryocytes water clear cytoplasm and sparse or no granules).3 Non- were evaluated for megakaryocytic alterations including dysplastic features include immature forms, emperipolesis, both dysplastic features (multiple separate nuclei, budding, cytoplasmic vacuolization and bare nuclei. micromegakaryocyte and hypogranular forms) and non- Immature megakaryocytes are young forms with scant dysplastic features (emperipolesis, immature, bare nuclei, bluish cytoplasm and lack lobulation. Megakaryocytes cytoplasmic vacuolization and budding). Dysplastic are considered to show budding if there is blebbing of alterations were considered significant only when 10% or cytoplasm on their surface. Emperipolesis has been defined more of the megakaryocyte observed show the change.5 by the presence of other cell within the cytoplasm of megakaryocyte.3 RESULTS Dysplastic megakaryocytic alterations are well known Out of 139 cases of thrombocytopenia, 86 cases (61.9%) in thrombocytopenia associated with myelodysplastic were observed in male and 53 cases (38.1%) were in syndrome (MDS). However, several studies have described female. Thrombocytopenia was most common in the age it’s occurrence in non-myelodysplastic haematological group of 20-39 years (38.8%; 54 cases) followed by that in conditions but scant data exist on their prevalence. 60-79 years of age group (24.5%; 34 cases). Thrombocytopenia, either isolated or in association with Table 1 shows common causes of thrombocytopenia. The bicytopenia or pancytopenia is one of the commonly commonest cause was megaloblastic anemia (31.7%) encountered haematological problems for which a bone followed by acute leukemia (27.3%) and ITP (23.7%). marrow study is usually performed. Bone marrow aspiration in thrombocytopenia is particularly helpful in differentiating Average number of megakaryocyte in megaloblastic the hypoproliferative causes e.g. aplastic anemia from that anemia was 18.34 and was normal in 47.4% of the cases. due to peripheral destruction of the platelet. Out of 33 cases of ITP, 31 (91%) had increased number of megakaryocytes, the average being 53.45. Table 2 shows Initially the study was designed to compare various average number of megakaryocyte per 10 LPFs in bone megakaryocytic alterations between MDS and non-MDS related thrombocytopenia which could not be performed Table 1: Common causes of thrombocytopenia due to the mere absence of MDS in the study period. Bone marrow aspiration Number of cases Percent This study was thus restricted to study the prevalence of various megakaryocytic alterations in non-MDS related Megaloblastic anemia 44 31.7 thrombocytopenia. ITP 33 23.7 Acute leukemia 38 27.3 MATERIALS AND METHODS Aplastic anemia 13 9.4 The study was a hospital based prospective observational Kalaazar 4 2.9 study done in National Academy Medical Science, Bir Idiopathic hypereosinophilia 3 2.2 Hospital from May 2010 to April 2012. All patients Multiple myeloma 2 1.4 3 presenting with platelet count less than 150,000/mm were Iron deficiency anemia 2 1.4 included in the study. A written consent was taken for every Total 139 100 case. All the relevant clinical data were collected. Manual 478 Choudhary PK et al. Table 2: Average number of megakaryocytes per 10 LPFs Bone marrow impression Number mean Absent Decreased Normal Increased Megaloblastic anemia 44 18.34 1/2.4% 7/16.0% 21/47.4% 15/34.2% ITP 33 53.45 0/0% 2/6.0% 1/3.0% 30/91% Acute leukemia 38 6.39 1/2.6% 33/87.0% 2/5.2% 2/5.2% Aplastic anemia 13 8.54 0/0% 9/69.2% 3/23.1% 1/7.7% Kalaazar 4 29.5 0/0% 0/0.0% 1/25.0% 3/75.0% Idiopathic hypereosinophilia 3 12.0 0/0% 1/33.3% 2/66.7% 0/0.0% Multiple myeloma 2 13.5 0/0% 1/50.0% 1/50.0% 0/0% Iron deficiency anemia 2 38.5 0/0% 0/0% 0/0% 2/100% Total 139 22.9 2/1.4% 53.38.2% 31/22.2% 53/38.2% Table 3: Prevalence of dysplastic and non-dysplastic Table 4: Prevalence of emperipolesis in various hemato- changes in various hematological disorders logical disorders Non- Bone marrow impression Dysplasia Total Bone marrow impression Absent Present Total Dyspiasia Megaloblastic anemia 43 1 44 Megaloblastic anemia 23/52.3% 21/47.7% 44 ITP 27 6 33 ITP 7/21.2% 26/78.8% 33 Acute leukemia 36 2 38 Acute leukemia 19/50% 19/50% 38 Aplastic anemia 8 5 31 Aplastic anemia 4/30.8% 9/69.2% 31 Kalaazar 3 1 4 Kalaazar 4/100% 0/0% 4 Idiopathic hypereosinophilia 1 2 3 Idiopathic hypereosinophilia 0/0% 3/100% 3 Multiple myeloma 2 0 2 Multiple myeloma 0/0% 2/100% 2 Iron deficiency anemia 1 1 2 Iron deficiency anemia 0/0% 2/100% 2 Total 121 18 139 Total 57/41% 82/59% 139 marrow aspiration. Dysplastic megakaryocytes in various anemia didn’t reveal immature megakaryocytes. hematological disorders are shown in table 3. Megaloblastic anemia was more likely to have dysplastic megakaryocyte Table 4 shows prevalence of emperipoleisis. Out of 13 cases (52.3%; n=23) followed by acute leukemia (50%; n=19) of aplastic anemia emperipolesis was found in 5 cases. and aplastic anemia (30.8%; n=4). Emperipolesis was also found in 6 out of 27 cases of ITP.
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