Hematological Profile in Pulmonary Tuberculosis

Hematological Profile in Pulmonary Tuberculosis

ORIGINAL RESEARCH Hematological Tuberculosis

Profile

in

Pulmonary

Parasappa Joteppa Yaranal, Toolhally Umashankar, Sadula Govindareddy Harish Background: Tuberculosis is a major public health problem in India. There is a paucity of literature in the hematological changes associated with tuberculosis, though tuberculosis is a common condition. Dr PJ Yaranal MD is Professor of Pathology, Kannur Medical College, Anjarakandy, Kannur, Kerala, India. Dr Umashankar T MD is Professor of Pathology, Father Muller Medical College, Mangalore, Karnataka, India. Dr Harish SG MD is Associate Professor of Pathology, Basaveshwara Medical College, Chitradurga, Karnataka, India.

Corresponding Author: Dr Umashankar T E-mail: [email protected]

Objective: To evaluate the hematological parameters in pulmonary tuberculosis patients who are positive for Mycobacterium tuberculosis bacilli in sputum. Materials and Methods: One hundred patients of fresh pulmonary tuberculosis with sputum positive for acid fast bacilli (AFB) were included and AIDS patients, disseminated tuberculosis and patients receiving ATT drugs were excluded in this study. The various hematological parameters were studied by means of hemogram by automated cell counter and peripheral smear examination. Results: Anemia was seen in 74% of patients. In spite of the infection, 71 patients had a normal leukocyte count. Leucocytosis as a response to infection was observed in 26 patients. Three patients had leucopenia. Thrombocytosis was observed in 24 patients while thrombocytopenia was observed in 9 patients. 99% patients had increased erythrocyte sedimentation rate (ESR). Two patients had pancytopenia. Conclusion: Variety of hematological abnormalities has been demonstrated in patients with pulmonary tuberculosis in the present study. While many of them are consistent with reported literature and reinforce the fact that they can be valuable tools in monitoring pulmonary tuberculosis such as anemia and increased ESR. Other findings such as thrombocytosis and pancytopenia suggest the need for further studied in this field. Keywords: Mycobacterium tuberculosis, Pulmonary tuberculosis, Anemia, Leucocytosis, Thrombocytosis, Pancytopenia, Erythrocyte sedimentation rate.

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International Journal of Health and Rehabilitation Sciences

Volume 2

Issue 1

Hematological Profile in Pulmonary Tuberculosis

INTRODUCTION Tuberculosis is a highly prevalent chronic infectious disease caused by Mycobacterium tuberculosis bacilli. Globally Mycobacterium tuberculosis infection remains at an epidemic level affecting one third of world population.1 The condition in India is equally alarming. About one third of India population is infected with Mycobacterium tuberculosis and the emergence of human immunodeficiency virus (HIV) infection has made the situation worse.2 Around 10% of tuberculosis cases are in the first and second decade of life. It affects three times as many men as women. 3 Reversible peripheral blood abnormalities are commonly associated with pulmonary tuberculosis. Insight into the relationship between hematological abnormalities and mycobacterial infection has come from an understanding of the immunology of mycobacterial infection. The atypical and varied spectrum of clinical presentation of tuberculosis poses a diagnostic and therapeutic challenge to the physicians. Little is known about the prevalence of these hematological abnormalities and the effect of antituberculosis treatment on the various hematological parameters in the Indian subcontinent. 4 This study was undertaken to analyses the hematological parameters in patients with sputum smear positive for AFB and to evaluate their diagnostic and prognostic significance.

MATERIALS AND METHODS During two years of period from September 2009 to August 2011, one hundred pulmonary tuberculosis patients’ hematological parameters were studied. The fresh pulmonary tuberculosis patients whose sputum was positive for AFB included in this study. Patients, less than 16-years of age, AIDS patients, disseminated tuberculosis cases and patients receiving ATT drugs were excluded from the study. Pertinent information regarding the history of illness was collected according to the questionnaire by personal interview. A thorough clinical examination was done and the findings were complemented by findings in case records. Ethical clearance was obtained from the institutional Ethical committee and informed 51

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consent was obtained from all patients participating in the study. The peripheral blood was evaluated for hemoglobin (Hb), total leukocyte count (TLC), differential leukocyte count (DLC), Platelet count, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) were analyzed using fully automated hematology analyzer Sysmex KX 21, using EDTA anticoagulated fresh venous blood samples. Along with these parameters erythrocyte sedimentation rate and peripheral blood smear (PS) examination was done to study the RBC and WBC morphology are included. The data was entered in Excel chart and all the hematological parameters were analyzed by using proportions or percentage.

RESULTS One hundred patients who were sputum positive for AFB were included in the study. There were 71 males and 29 females with mean age of 41 years. Mean age for males was 42 years and mean age for females was 35 years. 61% of patients were in age group of 20 – 50 years. 8% of the total population was below the age of 20years and 31% of the total population was above 50 years. The mean Hb level was 11.1 g/dl. In males the Hb value ranged from 6.9g/dl to 16.3g/dl with the mean being 11.5 g/dl. In females the mean Hb level was 10g/dl ranging from 7.1g/dl to 14.4g/dl. In 28% cases Hb was less than 10gm/dl (Table 1). The mean hematocrit value was 33%. Hematocrit values were ranges from 27.4 to 41.6 with mean of 34.5% in males and in females ranged from 25 to 40% with a mean of 32.5%. In 30% of cases hematocrit values less than 30%. Hence both Hb and hematocrit values are correlated almost in 30% of cases in pulmonary tuberculosis. The definition of anemia used in this study was hemoglobin concentration less than 13.5 g/dL in men and 12.5 g/dL in women (WHO Recommendation).5 Anemia was typed based on the MCV, MCH and peripheral smear findings. Anemia was present in 74 patients. 68.9% (51) men and 31% (23) women had anemia. Normocytic anemia was the most


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Hematological Profile in Pulmonary Tuberculosis Table1 Distribution of Hemoglobin according to Gender Male

Hb (g/dL)

No.

%

14 Total

30 28 11 71

42.3 39.4 15.5 100

Female Mean (Range ) 11.5g/dL (6.9 -16.3) -

%

07

24.0

common type and was found in 49 (66.2%) patients. Microcytic anemia was next common type and was seen in 22 patients. Three patients had macrocytic anemia in which the MCV was more than 100 fl (Table 2). In spite of the infection, 71 patients had a normal leucocyte count. Lecocytosis as a response to infection was observed in 26 patients of which 21(80.7%) were males and 5 (19.3%) were females and three patients had leucopenia. Of the26 patients, 20 patients with Leucocytosis had neutrophilia and three patients had monocytosis and lymphocytosis each (Table 2). Thrombocytosis was observed in 24 patients while thrombocytopenia was observed in 9 patients. Other 67 patients had a normal platelet count. Interestingly thromobocytosis was observed in patients who had leukocytosis (Table 2). In this study 99% of patient had increased ESR. Only one patient had a normal ESR. 13 patients had ESR ranging from 20 to 40 mm in first hour, 30 patients had ESR in the range of 40 – 60 mm in first hour, 35 patients had from 60 to 80 mm in first hr and 11 patients had ESR value more than 100 mm in first hr. The numbers of males were more in all ranges (Table 2). Two patients had peripheral pancytopenia.

DISCUSSION Tuberculosis continues to be an important communicable disease in the world and is a major public health problem in India. In fact, WHO has declared tuberculosis is a global emergency in 1993. Various hematological manifestations have been described in association with tuberculosis. There is paucity of literature about the hematologic abnormalities in pulmonary tuberculosis patients from Indian 52

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Mean (Range )

No.

09 12 01 29

Total

31.0 41.5 03.5 100

10 g/ dL (7.1-14.4) -

No.

%

09

09

39 40 12 100

39 40 12 100

Mean (Range) 11.1 g/dL (6.9 - 16.3) -

population. In the present study an attempt has been made to study a complete hematological profile in pulmonary tuberculosis. The prevalence of anemia in the present study was similar to the other studies2,5,6 and normocytic normochromic was the most common type. The bone marrow study by Singh KJ et al2 found blunted erythropoieitic response of bone marrow. Other authors have also reported a blunted erythropoietin response to anemia of untreated tuberculosis. It is postulated that the tumor necrosis factor–α (TNF- α) and other cytokines released by activated monocytes suppress the erythropoietin production leading to anemia.2 Although a normocytic normochromic anemia was most common in this study, other types of anemias including, microcytic (22%) and macrocytic (3%) were also noted. The incidence of macrocytic blood picture is similar to study done by Morris et al.6 Elevated serum ferritin found in almost all patients in other studies, probably due to its behavior as an acute phase reactant.6 Leucocyte response varied from leucocytosis to pancytopenia. Mild leucocytosis is documented in 8-40% of patients with pulmonary tuberculosis.3 The prevalence of leucocytosis in present study was similar to study done by Singh KJ et al.2 All patients with leukocytosis had neutrophilia and only three patients had monocytosis. Although, changes have been reported in relative number of lymphocyte and monocyte and polymormponuclear leucocytes, these had not proved useful either as clinical or prognostic value. 7 The reported prevalence of leucopenia in pulmonary tuberculosis is 1-4%. The results of present study are in agreement with these studies. Neutropenia was the predominant


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Hematological Profile in Pulmonary Tuberculosis Table 2 Peripheral Blood Findings in Tuberculosis Sl No. 1

2

3

4

Parameters Red Blood cells: Anemia Normocytic anemia Microcytic anemia Macrocytic anemia White Blood Cells: Normal count Leucocytosis Leucopenia Neutrophilia Lymphocytosis Monocytosis Platelets: Normal Thrombocytosis Thrombocytopenia Erythrocyte Sedimentation rate: Normal Increased: 20 - 40 mm/1hour 40 - 60 mm/1hour 60 - 80 mm /1hour >100mm/1hour

finding in these patients. The various pathophysiological mechanism implicated in neutropenia are poorly understood. However, it is a consequence of the combined effect of hypersplenism, excessive margination of neutrophil or marrow granulopoietic failure mediated by the T- lymphocyte showing granulopoietic inhibitor activity. Associated malnutrition may also result in neutropenia.8 Many authors reported lymphocytopenia in patients with pulmonary tuberculosis. The exact reason for the development of lymphocytopenia has not been elucidated. Nevertheless, the role of cytokine including TNF in the pathogenesis of lymphocytopenia has been suggested.2 Previous studies have documented pancytopenia in patient with disseminated and military tuberculosis and but it is a rare finding in patients with pulmonary tuberculosis. 9 In the present study two cases had pancytopenia and bone marrow examination was not done as the patients were not willing for further evaluation. A case of pancytopenia with tuberculosis has been reported by Puri MM et al10. They 53

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No. of cases

Percentage

74 49 22 03

74.00% 66.21% 29.72% 04.05%

71 26 03 20 03 03

71.00% 26.00% 03.00% 76.92% 11.53% 11.53%

67 24 09

67.00% 24.00% 09.00%

01 99 13 30 35 11

01.00% 99.00% 13.13% 30.30% 35.35% 11.11%

observed normocellular and normal maturation of all three cell series in the bone marrow and found a significant improvement in all parameters after antituberculous treatment. Splenomegaly was observed in patients with tuberculosis associated pancytopenia.2 The various postulated mechanisms for pancytopenia include splenic sequestration, immune mediated bone marrow suppression and a decreased bone marrow reserve. It has been suggested by Goldenberg3 that identification of pancytopenia or thrombocytopenia in association with tuberculosis suggests the possibility of drug toxicity or another underlying process and requires further evaluation. Thrombocytosis has been reported in patients with miliary or disseminated tuberculosis.9 It was a striking feature in pulmonary tuberculosis patients in a study done by Morris et al, as they had more than 50% patient with thromobocytosis.6 In the present study, 26% had thrombocytosis close to the findings of Singh KJ et al2 who found in 32% patients with thrombocytosis. The stimulus for


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Hematological Profile in Pulmonary Tuberculosis increased platelet production in reactive thrombocytosis is not clear.11 Various inflammatory cells, cytokines and mediators are involved in the formation of granulomatous lesions encountered in tuberculosis. Among them interleukin-6 (IL-6) has been known to promote platelet production.12 Since platelets have been proposed as immune cells in recent years, the distinctive morphologic features of platelets with higher PDW and MPV values in tuberculosis may be a reflection of an activated platelet form as observed for most other cells of the immune system. The ESR is seldom the sole clue to disease in asymptomatic person and is not a useful screening test. When the ESR is increased a careful history and physical examination can disclose the cause.13 Studies reported on the value of the ESR as a test of activity in pulmonary tuberculosis have concluded that the ESR is useful practical method of obtaining accurate and dependable information about the actual progress or retrogression of tuberculous lesion, before these can be demonstrated by other clinical and laboratory procedures. Changes in the sedimentation rate exactly parallel alteration in the tuberculous focus. Previous studies have documented an elevated ESR level in majority of patients1 which decreased significantly in those who sputum becomes negative. 99% of patients with increased ESR in the present study are in concordance with the reported literature. The study done by Al-Marri MR and Kirkpatrick MB14 found that children with symptomatic tuberculosis had significantly higher ESR values than asymptomatic children with tuberculosis and likewise children with positive culture for tuberculosis had significantly higher ESR values than children with negative tuberculosis cultures. Nevertheless, there was large range of individual values with considerable overlap, making it difficult to see how individual patient values could be of any utility in either diagnosing or excluding tuberculosis. They concluded that the ESR value is likely to be of little or no diagnostic utility in the diagnosis of childhood tuberculosis. 14

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CONCLUSION This study has shown the various hematological abnormalities which occurred in 100 patients with pulmonary tuberculosis. A complete hemogram was done in patients with sputum smear positive for AFB using automated cell counter. Anemia was frequently encountered in patients with pulmonary tuberculosis (74%) and normocytic normochromic anemia was the most common type. Leucocytosis occurred in 21%. Leucopenia with neutropenia and lymphocytopenia was observed in 3%. Thrombocytosis was seen in 26%. Majority of the findings are consistent with reported literature and reinforce the fact that they can be valuable tools in monitoring such as anemia and increased ESR. Other findings such as thrombocytosis and pancytopenia suggest the need for further studies in this field.

CONFLICTS OF INTEREST None declared

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Oliva VM, Cezario GAG, Cacto RA, Marcondes-Machado J. Pulmonary tuberculosis; haemotology, serum biochemistry and relationship with the disease condition. J Venom Anim Toxins Incl Trop Dis 2008;14:718. Singh KJ, Ahulwalia G. Sharma SK, Saxena R, Chaudhary VP, Anant M. Significance of hematological manifestations in patients with tuberculosis, J Asso Physicians Ind 2001; 49:788-94. Goldenberg AS. Hematologic abnormalities and mycobacterial infection. In, Williams NR, Stuart GM (ed). Tuberculosis. Boston, Little – Brown Company, 1996; 645-7. Vijayan VK, Sagal Das. Pulmonary tuberculosis In, Suredra Sharma (ed). Tuberculosis 1st edition. New Delhi, Jaypee Publishers, 2009; 217-27. Lee SW, Kang YA, Yoon YS, Um SW, Lee SM, Yoo CG et al: The prevalence and evolution of anemia associate with tuberculosis. J Korean Med Sci 2006;21:1028-32. Morris CD, Bird AR, Nell H. The hematological and biochemical changes in severe pulmonary tuberculosis. Q J Med 1989;73:1151-9.


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Hematological Profile in Pulmonary Tuberculosis 7.

Tanzeela T,Bashir MB, Yaqoob M. Comparative efficacy of different laboratory technique used in diagnosis of tuberculosis in human population. J Med Sci 2001;2:137-44. 8. Sharma SK, Pande JN, Singh YN, Verma K, Kathait SS, Khare SD et al. Pulmonary tuberculosis and immunologic abnormalities in miliary tuberculosis. Am Rev Respir Dis 1992; 145:1167-71. 9. Maartens G, Willcox PA, Benatar SR. Miliary tuberculosis: rapid diagnosis, hematologic abnormalities and outcome in 109 treated adults. Am J Med 1990;89:291-6. 10. Puri MM, Gupta K, Sigh RP, Gupta SP. A case of pulmonary tuberculosis with pancytopenia. J Int Med India 1998; 9:20-1. 11. Baynes RD, Flax H, Bothwell TH, McDonald TP, Atkinson TP, Chetty N et al. Reactive thrombocytosis in pulmonary tuberculosis. J Clin Pathol 1987; 40:676-9.

12. Kartaloglu Z, Cerrahoglu K, Okutan O, Ozturk A, Aydilek R. Parameters Of Blood Coagulation In Patients With Pulmonary Tuberculosis. The Internet Journal of Internal Medicine 2001; 2(2). Available fromURL:http://www.ispub.com/journal/the _internet_journal_of_internal_medicine/volu me_2_number_2_27/article/parameters_of_ blood_coagulation_in_patients_with_pulmo nary_tuberculosis.html. Accessed on 3rd October 2011. 13. Sox HC Jr, Liang MH. The erythrocyte sedimentation rate: Guidelines for rational use. Ann Intern Med 1986;104:515-23. 14. Al-Marri MR, Kirkpatrick MB. Erythrocyte sedimentation rate in childhood tuberculosis: is it still worthwhile? Int J Tuberc Lung Dis 2000;4:237-9.

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