|Year : 2019 | Volume
| Issue : 7 | Page : 2445-2449
Prevalence, characteristics, and predictors of tuberculosis associated anemia
Anirudh Mukherjee, Nidhi Kaeley, Minakshi Dhar, Subodh Kumar, Bharat Bhushan
Senior Resident General Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
|Date of Submission||16-Apr-2019|
|Date of Decision||19-Apr-2019|
|Date of Acceptance||07-May-2019|
|Date of Web Publication||31-Jul-2019|
Dr. Nidhi Kaeley
All India Institute of Medical Sciences, Rishikesh - 249 203, Uttarakhand
Source of Support: None, Conflict of Interest: None
Tuberculosis is an infectious disease caused by mycobacterium tuberculosis. It is one of the deadliest disease and a major burden on the healthcare system in India. India, a second most populous country in the world, has a very high global annual incidence of tuberculosis. Multiple hematological changes have been reported in patients with tuberculosis such as iron deficiency anemia, folate deficiency, and sideroblastic anemia. Aims and Objectives: The present study was planned to find the prevalence and characteristics of anemia in the new cases of pulmonary tuberculosis. The secondary objective was to assess the predictors of anemia in new cases of pulmonary tuberculosis. Methods: The retrospective study was carried out at a tertiary care hospital of Uttarakhand and included all the new cases of tuberculosis aged more than 18 years attending medicine outpatient and inpatient departments over a period of 1 year. Detailed demographic, clinical, and biochemical data were obtained from the hospital record section and tabulated. Results: Most patients with tuberculosis and anemia were more than 50 years of age. Clearly, males outnumbered females. Approximately, 80% patients were illiterates. A majority (71, 39.2%) of the patients had BMI within the range of 18.5 to 24.9 kg/m2. The most common symptoms of tubercular patients with and without anemia were cough, fever, breathlessness, and hemoptysis. However, pallor was the most common sign. Clearly, hematological indices were lower in patients with anemia. In total, 112 (60%) patients had mild anemia and 103 (56.9%) patients had normocytic normochromic anemia. Significant association was found between Body Mass Index (BMI) and anemia in patients with pulmonary tuberculosis. Similarly, severity of anemia co-related significantly with BMI of patients with pulmonary tuberculosis. BMI showed a significant correlation with hemoglobin, packed cell volume, mean corpuscular cell volume, and red cell distribution width (RDW). In addition, age showed a significant correlation with hemoglobin and RDW.Conclusion: Normocytic normochromic anemia is a common hematological abnormality in patients with pulmonary tuberculosis. Thus, it warrants frequent screening for anemia in all the cases of pulmonary tuberculosis to improve morbidity and mortality in these patients.
Keywords: Folate deficiency, mycobacterium tuberculosis, normocytic normochromic anemia
|How to cite this article:|
Mukherjee A, Kaeley N, Dhar M, Kumar S, Bhushan B. Prevalence, characteristics, and predictors of tuberculosis associated anemia. J Family Med Prim Care 2019;8:2445-9
|How to cite this URL:|
Mukherjee A, Kaeley N, Dhar M, Kumar S, Bhushan B. Prevalence, characteristics, and predictors of tuberculosis associated anemia. J Family Med Prim Care [serial online] 2019 [cited 2020 Jan 25];8:2445-9. Available from: http://www.jfmpc.com/text.asp?2019/8/7/2445/263764
| Introduction|| |
Tuberculosis is caused Mycobacterium tuberculosis. The cardinal features of the disease are cough with or without expectoration, intermittent fever, weight loss, decrease appetite, and hemoptysis. It has been observed that around one-third of the world's population is infected with pulmonary tuberculosis. The major hematological abnormality seen in patients with tuberculosis is anemia. The underlying pathogenesis of anemia in patients with tuberculosis is suppression of erythropoiesis by inflammatory markers, nutritional deficiency, and malabsorption syndrome., It has been observed that patients with tuberculosis associated anemia have reduced bone marrow iron. Thus, iron deficiency is a possible cause of anemia in these patients. It has been observed that anemia resolves with anti-tubercular therapy in patients., This study was done to study the prevalence and characteristics of anemia in newer cases of pulmonary tuberculosis.
| Materials and Methods|| |
The retrospective study was carried out at a tertiary care hospital of Uttarakhand. It included all the new cases of pulmonary tuberculosis aged more than 18 years of age attending medicine OPD or medical ward over a period of 1 year from May 2017 to May 2018. Ethical clearance was sought from the ethics committee. A new case of pulmonary tuberculosis was defined as a patient who has never received treatment for tuberculosis or who had taken antitubercular therapy (ATT) for less than 1 month. A sputum positive pulmonary tuberculosis was defined as a patient with one or more initial sputum smears examination (direct smear microscopy) acid-fast bacilli (AFB) positive or one sputum examination AFB positive and radiographic abnormalities consistent with active tuberculosis. All the cases of pulmonary tuberculosis categorized as relapse, treatment failure, and defaulters and chronic cases were excluded from the study. The detailed demographic and clinical data were obtained from the hospital record section and tabulated. Results of investigations such as complete hemogram, reticulocyte count, stool examination, serum iron, vitamin B12 and folic acid levels, general blood picture, and bone marrow examination (if done) were noted from the patient record files. The new cases of pulmonary tuberculosis were categorized as with and without anemia. Anemia was defined as per WHO guidelines, which are hemoglobin levels less than 12 gm/dl. Anemia was further subdivided as mild (11.9–10 gm/dl), moderate (9.9–8 gm/dl), and severe (<8 gm/dl) as per se verity. Microcytic anemia was defined as MCV (<80 fl), normocytic (MCV = 80–95 fl), and macrocytic (MCY > 95 fl). The results were analyzed as SPSS (version 17.0). A significance of difference between proportions was tested using Chi-square test. Comparison of continuous data was done using student unpaired t test. Pearson's product moment correlation coefficient was used to determine the correlation between different variables. A “P” value of < 0.05 was considered to be significant.
| Results|| |
The baseline characteristics of patients with pulmonary tuberculosis with anemia are enlisted in [Table 1]. Maximum (87, 48%) number of patients with anemia were more than 50 years of age. As evident, males outnumber female patients. More than 60% of the patients with pulmonary tuberculosis with and without anemia belonged to lower socio-economic status. Approximately, 80% of patients with pulmonary tuberculosis were illiterates. The other risk factors were alcoholism (44, 25.3%) and smoking (58,32.0%). Tubercular patients with anemia (107, 59.1%) had lower BMI as compared to patients without anemia (3, 4.2%). Cough followed by fever, palpitation, and breathlessness were common symptoms in patients with tuberculosis with and without anemia. Clearly, pallor (96, 53%) was more common in patients with anemia. The mean respiratory rate (22.6 ± 2.8) and mean heart rate (82.3 ± 11.7) were more in patients with tuberculosis with anemia. [Table 2] demonstrates a comparison of laboratory parameters in patients with pulmonary tuberculosis with and without anemia. The mean hemoglobin (9.65 ± 1.32), red blood cell count (3.32 ± 0.63 million/cumm), packed cell volume (PCV) (25.02 ± 3.13%), mean corpuscular cell volume (MCV) (81.11 ± 10.66 fl), and red cell distribution width (RDW) (17.25 ± 2.9) were lower in patients with tuberculosis with anemia. There were no significant sputum positivity rates of tuberculosis patients with and without anemia. [Table 3] depicts the severity of anemia in patients with tuberculosis. In total, 112 (61.8%) patients presented with mild anemia and maximum 103 (56.9%) patients had normocytic normochromic anemia. [Table 4] shows correlation of various predictor variables and hematological parameters. There was a significant correlation between BMI and hemoglobin, PCV, MCV, and RDW. Age showed a significant correlation with hemoglobin and RDW. Duration of disease correlated significantly with only RDW. [Table 5] shows correlation of severity of anemia with social and demographic parameters. Age, gender, socio-economic status, literacy, and duration of disease did not show significant correlation with BMI and severity of anemia. [Table 6] shows that age and BMI had significant correlation with hemoglobin levels on univariate analysis, but by multivariate analysis, only BMI was found to be an independent predictor for hemoglobin.
|Table 1: Demographic and clinical profile of patients of pulmonary tuberculosis with anemia and without anemia|
Click here to view
|Table 2: Comparison of laboratory parameters of patients of pulmonary tuberculosis with and without anemia|
Click here to view
|Table 3: Types and morphological variants of anemia in patients with pulmonary tuberculosis|
Click here to view
|Table 4: Correlation of various predictor variables and hematological parameters|
Click here to view
|Table 5: Correlation of severity of anemia with various social and demographic parameters|
Click here to view
|Table 6: Predictors of hemoglobin levels by multiple linear regression analysis|
Click here to view
| Discussion|| |
Anemia is a known complication of pulmonary tuberculosis. Both inflammation and iron deficiency anemia are proposed mechanisms of anemia in patients with pulmonary tuberculosis. The reported prevalence of anemia in patients with pulmonary tuberculosis ranges from 20 to 94%. In our study, around half of the tubercular patients with anemia were more than 50 years of age. Previous studies have also reported age as a significant risk factor of anemia in patients with pulmonary tuberculosis. Aging has been associated with increased duration of chronic disease, poor nutrition, reduced marrow cellularity, and decreased vitamin B12 levels. Another important cause of anemia in patients with pulmonary tuberculosis is drug induced. The anti-tubercular drugs such as isoniazid, cycloserine, and pyrazinamide have been found to cause sideroblastic anemia. These drugs interfere with the conversion of vitamin B6 to its active coenzyme, thus inhibiting the 5-aminolevulinic acid synthase activity. Although folate deficiency has also been reported in many of the tubercular patients, the incidence of megaloblastic anemia is low in these patients. Rare cases of myelofibrosis associated with disseminated tuberculosis have been described in the past. In our study, 181 (71.8%) cases of pulmonary tuberculosis with anemia were studied out of 252 cases. In a similar study by oliveria et al., 104 (89.2%) of pulmonary tuberculosis had anemia were observed and Hussain et al. observed 62% cases of miliary tuberculosis had anemia., In our study, anemia was more common in male (74.5%) patients with pulmonary tuberculosis as compared to the females (25.4%). Similar results were reported by a study conducted by oliveria et al. However, Khurram et al. did not find a statistical difference between gender and prevalence of anemia. In our study, maximum number of patients [61.8%] had mild anemia. A similar result was observed by lee et al. In our study, 103 (56.9%) patients had normocytic normochromic anemia; Lee et al. described 72% patients had normocytic normochromic anemia and was the most common type of anemia in patients with pulmonary tuberculosis. Similarly, Bashir et al. observed that most of the patients with pulmonary tuberculosis had anemia of chronic disease (15,34%) followed by iron deficiency (12,27%), macrocytic anemia (2,5%), and normocytic normochromic anemia (8,18%). In our study, 107 (59.1%) patients of pulmonary tuberculosis with anemia were malnourished (BMI < 18.5 kg/m 2). Malhotra et al. described a similar result, showing lower BMI in anemic patients of pulmonary tuberculosis. Previous studies have highlighted that malnourished tubercular patients have reduced levels of iron and zinc as compared to healthy patients. Iron deficiency has been found to impair T-cell immunity by interfering with the effector cell activity. Past studies have also reported a possible correlation between prediction of treatment failure with low ferritin levels. In our study, smoking has been found to be an independent risk factor of anemia in patients with pulmonary tuberculosis. Smoking causes virulent changes in the respiratory tree. This facilitates adherence of Mycobacterium to the airway epithelial cells, leading to TB infection. In our study, cough was the most common symptom in patients with pulmonary tuberculosis, with and without anemia. However, there was no significant difference between the two groups of patients with and without anemia. In a study conducted by Sahirat madja et al., anemia was most common in patients with longer duration of cough. Our study did not show a significant association between age of the patient and presence of anemia. Similar results were observed by a study conducted by Majur et al. In the current study, anemia was more common in patients belonging to lower socio-economic background. This result was confirmed by the study conducted by Malhotra et al. In our study, significant correlation was observed between BMI and hemoglobin, PCV, MCV, and RDW. Age showed a significant association with hemoglobin and RDW. In a similar study conducted by Oliveria et al., anemia has significant association with BMI, MCV, RDW, and ESR. Tuberculosis is a chronic infectious disease and is affected by multiple demographic and socio-economic parameters. It leads to multiple complications. Anemia is one of them. Taking into consideration, the large burden of anemia in our study population, categorization of severity, and treatment of anemia deserves a priority setting. Dual burden of HIV infection and tuberculosis is on the rise. Anemia has been found to delay the sputum conversion in patients with pulmonary tuberculosis in a dose-dependent manner. This underscores the role of primary care physician in these patients. Further studies are needed to assess the effect of treatment of anemia on final clinical outcomes of these patients.
The prompt recognition and treatment of anemia in these patients can improve their overall well-being significantly. Thus, the treatment of tuberculosis involves a combined role of a medical physician, family physician, and chest physician.
| Conclusion|| |
Anemia is a common hematological abnormality in new patients of pulmonary tuberculosis. Mild anemia and normocchromic normocytic anemia is the most common type of anemia. Severity of anemia has significant association with nutritional status of the patients assessed by BMI. BMI is an independent predictor of anemia in patients of pulmonary tuberculosis. Thus, frequent occurrence of anemia in new cases of pulmonary tuberculosis demands routine screening for anemia in all the cases of pulmonary tuberculosis. Thus, the role of family physician is of paramount importance who can identify, investigate, and treat anemia in patients of pulmonary tuberculosis. This will not only improve the overall wellness of these patients but also improve mortality and morbidity in these patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Park K. Park's Textbook of Preventive and Social Medicine. 23rd
ed. Jabalpur (India):Banarsidas Bhanot; 2009. p. 159.
Kritski A, Cataldi A, Reyes A, Martin A, Gicquel B, Martin C, et al
. BMC Microbiol 2007;9:39.
Morris CD, Bird AR, Nell H. The hematological and biochemical changes in severe pulmonary tuberculosis. QJ Med 1989;73:1151-9.
Schwenk A, Macallan DC. Tuberculosis, malnutrition and wasting. CurrOpin Clin NutrMetab Care 2000;3:285-91.
Koch A. Tuberculosis: Distribution, risk factors, mortality. Immunobiology 1994;191:325-36
World Health Organization. Tuberculosis. WHO Report 2012. Geneva, Switzerland.
World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System.WHO 2011. Geneva, Switzerland.
Tefferi A. Anemia in adults: A contemporary approach to diagnosis. Mayo Clin Proc 2003;78:1274-80.
Espinal MA, Laszlo A, Simonsen L, Boulahbal F, Kim SJ, RenieroA. Global trends in resistance to antituberculosis drugs: WHO. Inernational Union agains ttuberculosis and lung disease working group on Antituberculosis Drug Resistance Surveillance. N Engl J Med 2001;344:1294-303.
Gladwion M, Trattler B. Clinical Microbiology. 3rd
ed. United States of America. Miami: Med Master. Inc; 2007.p. 106-11.
Hoffbrand AV, Pettit JE. Essential Haematology. 3rd
ed. United Kingdom: Blackwell Science; 1993.p. 209-377.
Kaminskaia GO, AbdullaevRI. Iron metabolism in patients with different variants of pulmonary tuberculosis. Probl Tuberk 2002;49-51.
Karyadi E, Schultink W, Nelwan RH, Gross R, Amin Z, Dolmans WM, et al
. Poor micronutrient status of active pulmonary tuberculosis patients in Indonesia. J Nutr 2000;130:2953-8.
Laraque F. Performance of nucleic acid amplification test for diagnosis of tuberculosis inalargeurban setting. Clin Infect Dis 2009;49:46-54.
Oliveira M, Delogo K, Oliveira H, Ruffino-Netto A, Kritski A, Oliveira M. Anemia in hospitalized patients with pulmonary tuberculosis. J Bras Pneumol 2014;40:403-10.
Hussain S, Irfan M, Abbasi M. Clinical characteristics of 110miliary tuberculosis patients from alowHIV prevalence country. Int J Tuberc Lung Dis 2004;8:493-9.
Khurram M, Mizhi I, Arshad I, Khar H. Factors affecting relapse of tuberculosis. JRMC 2009;13:44-7
Lee S, Kang Y, Lee S, Yoo C, Kim Y, Han S. The prevalence and evolution of anemia associated with tuberculosis. J Korean Med Sci 2006;21:1028-32.
Baynes RD, Flax H, Bothwell TH, Bezwoda WR, Atkinson P, Mendelow B. Red blood cell distribution width in the anemia secondary to tuberculosis. Am J Clin Pathol 1986;85:226-9.
Mallhotra P, Kumari S, Kumar R, Verma S. Prevalence of anemia in adult rural population of north India. J Assoc Physicians India 2004;52:18-20.
Karyadi E, Schultink W, Nelwan RHH, Gross R, Amin Z, Dolmans WM, et al
. Poor micronutrient status of active pulmonary tuberculosis patients in Indonesia. J Nutr 2000;130:2953-8.
Weiss G. Iron and immunity: A double-edged sword. Eur J Clin Invest 2002;32:70-8.
Isanaka S, Aboud S, Mugusi F, Bosch RJ, Willett WC, Spiegelman D, et al
. Iron status predicts treatment failure and mortality in tuberculosis patients: A prospective cohort study from Dar es Salaam, Tanzania. PLoS One 2012;7:e37350.
Visser ME, Sted MC, Walzl G, Warren Rob, Schomaker M, et al
. Baseline predictors of sputum culture conversion in pulmonary tuberculosis: Importance of cavities, smoking, time to detection and w-beijing genotype. PloS One 2012;7:e29588.
Sahiratmadja E, Wieringa FT, Crevel R, Visser AW, Adnan I, Alisjahbana B, et al
. Deficiency and NRAMP1 polymorphisms (INT4, D543N and 3'UTR) do not contribute to severity of anaemia in tuberculosis in the Indonesian population. Br J Nutr 2007;98:684-90.
Monjur F, Farhana R. A cross-sectional study of morphological types of anemia in pulmonary tuberculosis patient and associated risk indicators in a selected hospital of Dhaka city, Bangladesh. I JChem Environ Biol Sci 2014;4:215-9.
Nagu TJ, Spiegelman D, Hertzmark E, Aboud S, Makani J, Matee MI, et al
. Anemia at the initiation of tuberculosis therapy is associated with delayed sputum conversion among pulmonary tuberculosis patients in Dar-es-Salaam, Tanzania. PLoS One 2014;9:e91229.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]