Bone Marrow Morphology in Peadiatric Mortalities Associated With Severe Acute Respiratory Illness at Kenyatta National Hospital

Abstract

Background In Kenya, severe acute respiratory tract infections (SARI) are the leading cause of death among children. The predominant mechanism of death is related to respiratory disease. These children frequently have hematologic abnormalities such as anemia, leukocytosis, thrombocytopenia and thrombocytosis. There is no African series that has examined the bone marrow morphological features in SARI mortalities. Asian and Eastern European series have identified haemophagocytic syndrome as a prominent feature in SARI mortalities. In Kenya, the contribution of the haemophagocytic syndromes and the diagnostic potential of bone marrow biopsies in SARI patients are unknown. In addition, the contribution of specific infectious disease morbidity to bone marrow pathology is also unclear. Objectives: The broad objective was to describe the morphological changes in bone marrow obtained from autopsies of SARI related mortalities in children under 5 years. The specific objectives were to describe the hematopoietic and histiocytic characteristics of bone marrow in pediatric SARI mortalities and to correlate the bone marrow morphological findings to SARI etiology. Study Design: Cross- Sectional Descriptive Study. Study Site: Anatomic Pathology core research and Unit of Haematology and Blood Transfusion laboratory, Department of Human Pathology, University of Nairobi. Study Population: These were SARI mortalities at Kenyatta National Hospital among infants and children aged 1-59 months that occurred between August, 2014 and December, 2015. The autopsies were performed on sixty four eligible SARI mortalities during that period as part of a larger study, titled ‘Pediatric Respiratory Epidemiology Surveillance Study (PRESS)’. Study Procedures: Fifty nine archived formalin fixed paraffin embedded (FFPE) bone marrow tissue specimens from the PRESS study were retrieved, sectioned and stained with Hematoxylin and Eosin (H/E), reticulin, modified Grunwald Giemsa (MGG), Periodic Acid Schiff (PAS) and Perl’s Prussian Blue. The specimens were examined using light microscopy by the principal investigator, hematopathologist and anatomic pathologist. These were examined using a standardized Royal College of Pathologists of Australia (RCPA) 2014 protocol approach. Variables were bone marrow cellularity, and nature of erythropoiesis, nature of myelopoiesis, megakaryocytes, lymphocytes, plasma cells, histiocytes and hemophagocytosis. Data was coded, cleaned and analyzed using statistics and data version13. Numeric variables were summarized using means (standard deviations) or medians (interquartile range) that were reported in histograms and dot plots. Categorical variables were summarized using frequencies and proportions that were reported in tables. Chi-square test of homogeneity was done to compare the distribution of morphological findings by type of infection. The chi-square statistic and corresponding p-values were reported. Results: Fifty two bone marrow biopsies were satisfactory for evaluation. The age range of the study population was 1 to 48 months with a median of 8 months. Females were 32 (54.2%) cases.The total blood count showed a mean hemoglobin level of 9.42 and standard deviation of 1.80, white blood cell count(WBC) had a median of 13 and Interquartile range(IQR) of 8.1. Of the 52 bone marrow biopsies evaluated, H&E stained well in 47 (90.4%) cases. Normal cellularity was observed in 35 (67%) cases. Erythropoiesis was normal in 25 (48%) cases) increased in 16 (30.8%) cases and reduced in 11 (21%) cases. Granulopoeisis was increased in 31 (59.6%) cases and reduced in 7 (13.5%) cases. Left shift granulopoeisis was reported in 38 (73.1%) cases. Megakaryopoesis was well represented in 40 (76%) cases. Plasma cells were increased in 5 (9.6%) cases and lymphocytes increased in 15(28%) cases. Histiocytosis was seen in 14 (26.9%) cases and Histiocytic Hyperplastic Hemophagocytosis (HHH) was present in 13 (25%) cases: mild HHH in 6 (11.4%) cases, moderate HHH in 2 (3.9%) cases and severe HHH in 2(3.9%) cases. Bone marrow hypoplasia with HHH was reported in 3 (5.8%) cases. Evidence of infection seen in the bone marrow were tuberculosis (n=1), malarial pigment (n=2) and parvovirus related changes (n=1). The finding of HHH was not significantly associated with any particular pattern of infection. There was no significant association between type of infection and presence of HHH. There was no association between bone marrow morphology and the infectious etiological agent. Conclusion: The main changes observed in bone marrow were granulocytic hyperplasia (59.6%), erythroid hyperplasia (30%) and histiocytosis (26.9%). Dyplasias involving the erythroid (44%) and myeloid lineages (14%) were common features. Hemophagocytosis (25%) was a significant finding in Kenyan SARI mortalities .