European Journal of Cardiovascular Medicine

Tuberculosis is a highly prevalent chronic infectious disease caused by mycobacterium tuberculosis bacilli. It is also highly infectious disease in which single patient may have devastating effects on tuberculosis control program by infecting large number of people. It mainly cause infection of the lungs (Pulmonary TB) but it can affect almost any tissue and organs of the human body (Extra pulmonary TB) [2-5].

Globally mycobacterium tuberculosis infection remains at an epidemic level affecting one third of world population and hence they are at risk of developing active TB disease. The burden of TB is highest in Africa and Asia [1].

As a developing country, condition in India is also equally alarming. India is the country with highest TB burden accounting for two-third (28%) of global TB cases. About 40% of India population is infected with mycobacterium tuberculosis [1].

According to global TB reports 2022, the incidence of TB, which is new TB cases per year, in India of 2021, 210 (par 1 lac population) and compared to the baseline year of 2015, there has been an 18% decline [3].

Tuberculosis is the ninth leading cause of death worldwide and the leading cause from a single infectious agent. India accounted for 36% of the global TB related deaths among HIV negative people. The emergence of HIV infection made the situation worse. Now tuberculosis leading killer among HIV positive people [1][4].

Accurate and rapid diagnosis is the key to control the disease but, the current routine diagnostic test for TB (chest X-ray, culture, tuberculin skin test and sputum smear microscopy) all have their limitation [6-9].

Reversible peripheral blood abnormality are commonly associated with pulmonary tuberculosis and These abnormalities are useful indicators providing a clue to diagnosis, assessing the prognosis, and including the complication of underlying infection and response to therapy [1].

Though hematological abnormalities associated with TB have been well recognized for nearly a century, not many comprehensive studies exist which describe the prevalence and relationship with the severity of the disease. Hematological changes have been observed with pulmonary, extra pulmonary and disseminated TB and usually reversible with ATT [12-17].

Aim of the study to hematological parameter namely Hb (Hemoglobin), total RBC count, Total WBC count, ESR (Erythrocyte Sedimentation Rate) and platelets in pulmonary tuberculosis.

This prospective study conducted in PDU medical college and hospital, Rajkot, Gujarat from April 2021 to March 2022. Blood sample sent to clinical laboratory, Department of pathology, where peripheral smear was prepared from EDTA sample and data evaluated.

INCLUSION CRITERIA:

Diagnosed tuberculosis patients including

Pulmonary tuberculosis. Extra pulmonary tuberculosis. MDR tuberculosis.

EXCLUSION CRITERIA:

Non tuberculosis patients.

The collection of blood was done at our central collection center. Two ml of blood drawn for each hematological study in tubes contain EDTA as anti-coagulants to prevent clotting of blood. Each sample was labeled and given a special number together with the patient name and registration number.

Method of blood collection:

Select a suitable site for venipuncture, by placing the tourniquet 3 to 4 inches above the selected puncture site on the patient. See below for venipuncture site selection. Do not put the tourniquet on too tightly or leave it on the patient longer than 1 minute. Next, put on non-latex gloves, and palpate for a vein.

When a vein is selected, cleanse the area in a circular motion, beginning at the site and working outward. Allow the area to air dry. After the area is cleansed, it should not be touched or palpated again.

If you find it necessary to reevaluate the site by palpation, the area needs to be re-cleansed before the venipuncture is performed. Ask the patients to make a fist; avoid “pumping the fist.” Grasp the patient’s arm firmly using your thumb to draw the skin taut and anchor the vein. The needle should from a 15-30 degree angle with the arm surface. Avoid excess probing.

When the last tube is filling, remove the tourniquet; remove the needle from the patients arm using a swift backward motion. Place gauze immediately on the puncture site. Apply and hold adequate pressure to avoid formation of a hematoma. After holding pressure for 1-2 minutes, tape a fresh piece of gauze or band- aid to the puncture site.

Dispose of contaminated materials/supplies in designated containers. The larger median cubital and cephalic veins are the usual choice, but basilic vein on the dorsum of the arm or dorsal hand veins are also acceptable. Foot veins are a last resort because of the higher probability of complication.

After collecting the blood it was transfused into a properly labeled vacuette. This vacuette was used for analyzing various hematological parameters like hemoglobin (HB), RBC count, RDW, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin  concentration (MCHC), total leucocyte count (TLC), differential leukocyte count (DLC), platelet count with the help of automated hematology analyzer.

Along with these parameters erythrocyte sedimentation rate (ESR), packed cell volume (PCV) and peripheral blood smear (PS) examination was done to study the RBC and WBC morphology.

Materials needed for study:

Disposable plastic syringes of 2 ml and disposable needles of 23 & 24 G.

EDTA vacuette.

Glass slides.

Stain: Field stain (Methanol as fixative).

Microscopic: Olympus CX 21 i.

Automated hematology analyser: Nihon Kohden Celtac ά. And Mindary BC-6200

Automated ESR instrument.

Total 850 patient’s samples were studied in this study. Various hematological parameters were noted by automated hematology analyzer and peripheral smear was also studied from each sample.

The following observations were noted:

Table 1: Age wise distribution of pulmonary and extra pulmonary tuberculosis.

Graph 1: Age wise distribution of pulmonary and extra pulmonary tuberculosis.

In our study, 24.59% of patients were in the age group of 21 -30 years in the pulmonary and extra pulmonary TB. Hence, both the disease predominantly affects adults. Second peak in pulmonary tuberculosis is between the age of 41 to 50 years (19.25%) and in extra pulmonary tuberculosis second peak is between the age of 11 to 20 years (15.53%)

Table 2: Gender wise distribution of Tuberculosis.

In our study, 66.71% were males and 33.29 % were females. In the pulmonary tuberculosis 353(41.53%) were male and 130 (15.29%) were female. In  extra pulmonary tuberculosis 214 (25.18%) were male and 153 (18%) were female. Hence males dominated in both groups.     There was a male predominance (66.71%) in both pulmonary and extra pulmonary tuberculosis.

Table 3: Gender wise distribution of Extra pulmonary sites.

There are most common extra pulmonary site is lymph node 98 (26.70%). Followed by abdominal 94(25.61%) and  third is plural 64(17.44%) in both gender. least common site is and Milliary 2(0.54%) and pericardial 1(0.27%).

Table 4: Prevalence of Anemia in Male and Female.

Out of 850 patients of both pulmonary and extra pulmonary tuberculosis 253 (29.76%) patients had Normal Hb level. Overall 597 (70.24%) patients have anemia, among them 411(72.66%) patients are male and 186 (65.72%) patients are female.

Graph 2: Prevalence of Anemia in Male and Female.

Table 5: Severity of anemia

Among the anemia patients 597, 305 (51.09%) patient’s hemoglobin is between 7 to 10 gm% mild anemia, 227 (38.08%) patients have moderate anemia and 65 (10.89%) patients have severe anemia <7 gm%.

Table 6: Types of anemia occurs in patients of tuberculosis.

Graph 3: Gender wise distribution of Anemia in patients of tuberculosis.

[NC NC Anemia- Normochromic normocytic anemia, HC MC Anemia- Hypochromic microcytic anemia, MC Anemia- Macroovalocytic anemia, DM Anemia- Dimorphic Anemia.

Most common type of anemia: Out of 597 anemic male & female, 314 (52.60%) patients have Normochromic Normocytic anemia. Out 411 male, 217 (52.80%) and out of 186 female, 97 (52.15%) have this type of anemia.

Second most common type of anemia: Out of 597 anemic male and female, 251 (42.04%) patients have Hypochromic microcytic anemia. Out of 411 male, 173 (42 09%) and out of 186 female, 80 (43.01%) have this type of anemia.

Only 3.02% cases show Macroovalocytic anemia, while only 2.34 % cases show Dimorphic anemia.

Table 7: ESR value

In this study 92.35% of patients with tuberculosis had increased ESR value. Among  567 male patients , 522 (92.06%) patients show raised ESR value, while Among 283 female patients, 273 (96.47%) patients show raised ESR value. 140 (16.47%) patients had an ESR value of 20-40 mm/hr, 225 (26.47%) patients had ESR in the range of 40-60 mm/hr, 378 (44.47%) patients had ESR in the range of 60-80 mm/hr and 42 (4.94%) patients had ESR value above 80 mm/hr.

Table 8: Total leucocyte count.

Despite the infection, 442(52%) patients had a normal leucocyte count. Leucocytosis as a response to infection was observed in 367 (43.18%). Out of which 204 (42.24%) patients of pulmonary tuberculosis and 163 (44.41%) patients of Extrapulmonary tuberculosis. Only 41 (4.82%) patients had leucopenia.           

Graph 4: Percentages of leucocyte counts.                                    

Table 9: Percentages of Different types of Leucocytosis

Out of 850 cases, 442 (52%) patients having Normal WBC count, while 367 (43.18%) patients having leucocytosis and out of 367 patients 265 (72.20%) patients having neutophilic leucocytosis and 91 (24.79%) patients have lymphocytic leucocytosis

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 tuberculosis patients from Indian population. In the present study an attempt has been made to study a complete hematological profile in tuberculosis [1-5].

This study was conducted in P.D.U. Medical College and hospital, Rajkot from April 2021 to March 2022 with 850 patients of pulmonary and extrapulmonary tuberculosis in which 567 Male and 283 were female.

Table 10: Age wise comparison study.

There was variation in age with high incidence in 3^rd decade followed by 5^th decade and 4^th decade in present study. In patel et al (2022, Rajasthan) study high incidence in 5^th decade followed by 4^th decade and 3^rd decade and in shah et al (2022, Gujrat) study high incidence in 5^th decade followed by 6^th and 4^th decade. So 3^rd, 4^th and 5^th decade is more common for tuberculosis infection [14][17].

Table 11: Gender wise comparison study.

We have reported 66.71% cases of tuberculosis in men as compared to 33.29% cases in women in present study. Similar findings were correlated well with other studies like Patel et al. (2022, Rajasthan), Shah et al.(2022,Gujrat), Pj yaranal.(2013,Keral) and Palanisawamy et al.(2021,Tamil nadu) that male is predominant  in tuberculosis [2][8][14][17].^.

Table 12: Comparison of Anemia with other study.

In the present study, the severity of anemia was assessed by hemoglobin level. We have reported 38.02% cases with mild anemia, 51.09% cases with moderate anemia, and only 10.89% of the patients had severe anemia. Similar findings seen in patel et al (2022, Rajasthan), Abay et al (2018, Hindawi), and pj yaranal et al.(2013, Keral). while in Shah et al.(2022, Gujrat) reported 50% cases with mild anemia [2][4][14][17].

Table 13: Comparison of type of anemia.

Normochromic normocytic anemia is more common in present study followed by Hypochromic microcytic anemia and less common is macroovalocytic anemia (3.02%) and Dimorphic anemia (2.34%). Similar findings seen in Patel et al (2022,Rajasthan,) Normochromic normocytic anemia (64.6%) , PJ yaranal et al.(2013, keral) Normochromic normocytic anemia (66.21%) and in shah et al (2022, Gujrat ) hypochromic microcytic anemia (52%) was more common [2][14][17].

Table 14: Comparison of ESR value.

In the present study, 92.35% patients are with increased ESR, which is almost similar with PJ Yaranal et al (2013,Keral )  and shah et al.(2022, Gujrat) study having 99 % and 98% patient with raised ESR. More common ESR was between the 60 – 80 mm in all study above mentioned.     

Table 15: Comparison of differential leucocyte count.

In our study the commonest leucocyte abnormality in our study were leucocytosis (43.18%), neutrophilia (46.59%), lymphocytosis (18.12%), lymphopenia (12.35%), leucopenia (4.82%) and neutropenia (2%). Our findings were consistent with study by shah et al. (2022, Gujrat) which show neutrophilia in 56% cases, leucocytosis in 43.18% cases, lymphopenia in 16%, neutropenia in 4% cases, leucopenia in 4% cases but variation in lymphocytosis which is seen in 4% cases. Compare to our findings  Patel et al. (2022 Rajasthan)  found leucocytosis in 28.8%, neutrophilia 56.8%, lymphocytosis 13%, and higher the findings of lymphopenia 37.7%, neutropenia 13.7%, and leucopenia 15.8% than present study. The prevalence of neutrophilia  76.92% is higher in PJ yaranal et al  (2013,Keral) study.[9-11]

Table 16: Comparison of platelet count.

 In present study we have found 32.47% cases with thrombocytosis which is similar to patel et al (2022 rajasthan) 32.9%, PJ yaranal et al (2013 ,Keral ) 24% and Yasmeen batool et al (2022 Pakistan) 26.2% while highly increased in  Shah et al (2022 Gujrat) 70%. And 6% cases with thrombocytopenia found in present study which is similar to patel et al (2022, Rajasthan) 15.8%,  Pj yaranal et al (2013, keral ) 9% and Yasmeen batool et al.10.6% and Shah et al (2022, Gujrat) 5% ^[2][14-17].

This study has shown the various hematological abnormalities which occurred in 850 patients with tuberculosis at P.DU. Medical College, Rajkot. A  complete hemogram was done in patients of tuberculosis using automated cell counter and automated ESR instrument.

Maximum numbers of cases found in 3^rd decade followed by 5^th decade and 4 th decade.  Anemia was frequently encountered in patients with tuberculosis (70.24%).                        Among anemic patients most patients (51.09%) have moderate degree of anemia with Hemoglobin level between 7 - 10 gm/dl and (38.02%) have mild degree of anemia with hemoglobin level between 10.1 - 12.9 for male and 10.1 - 11.9 for female. Only few patients (10.89%) have severe degree    of    anemia with hemoglobin level between <7 gm/dl.   Normocytic Normochromic anemia was the most common type of anemia (52.60%), Followed by hypochromic microcytic anemia (42.04%). Increased ESR is the commonest finding associated with tuberculosis (92.35%). Leucocytosis occurred in (43.18%) cases, among them (72.20%) cases show, Neutrophilia while (24.79%) cases show Lymphocytosis. Most cases have normal platelet count but thrombocytosis was seen in (32.47%) cases.  

Majority of the findings are consistent with reported literature and reinforce the fact that they can be valuable tools in diagnosis and monitoring the disease. These types of hematological abnormalities are quite common in patients with tuberculosis and physicians must maintain a high index of suspicion for diagnosis of tuberculosis in patients with these abnormalities.

1. World Tuberculosis Report 2022 : WHO
2. PJ yaranal, Umashankar T, Harish SO; Hematological Profile Tuberculosis (International Journal of Health and Rehabilitation Scenes Vol 2. 1, January 2013).
3. Singh KJ, Ahluwalia G, Sharma SK, Saxena R, Chaudhary VP, Anant M. Significance of haematological manifestations in patients with tuberculosis. The Journal of the Association of Physicians of India. 2001 Aug 1;49:788-90.
4. Abay F, Yalew A, Shibabaw A, Enawgaw B. Hematological abnormalities of pulmonary tuberculosis patients with and without HIV at the University of Gondar Hospital, Northwest sEthiopia: a comparative cross-sectional study. Tuberculosis research and treatment. 2018 Dec 30;2018.
5. Vijay Babu C. 2008 Hematological Profile of Pulmonary Tuberculosis Patients With and Without HIV (Doctoral dissertation, Madurai Medical College, Madurai).
6. Morris CD, Bird AR, Nell H. The hematological and biochemical changes in severe pulmonary tuberculosis. QJM: An International Journal of Medicine. 1989 Dec 1;73(3):1151-9.
7. Sullivan PS, Hanson DL, Chu SY, Jones JL, Ward JW, Disease Group TA. Epidemiology of anemia in human immunodeficiency virus (HIV)-infected persons: results from the multistate adult and adolescent spectrum of HIV disease surveillance project. Blood, The Journal of the American Society of Hematology. 1998 Jan 1;91(1):301-8.
8. Palanisawamy A. A study on hematological profile in pulmonary tuberculosis in south rural part of Tamil nadu. International Archives of integrated medicine.2021 Nov:8(11):1-8.
9. Olive VM, Cezario GA, Cacto RA, MarcondesMachado J. Pulmonary tuberculosis: Hematology, serum biochemistry and relationship with the disease condition. J Venom Anim Toxins Incl Trop Dis. 2008;14:71-8.
10. Lee SW, Kang YA, Yoon YS, Um SW, Lee SM, Yoo CG, Kim YW, Han SK, Shim YS, Yim JJ. The prevalence and evolution of anemia associated with tuberculosis. J Korean Med Sci. 2006 Dec; 21(6): 1028-32.
11. Olaniyi JA, Aken'Ova YA. Haematological profile of patients with pulmonary tuberculosis in Ibadan, Nigeria. Afr J Med Med Sci. 2003 Sep;32(3):239-42.
12. Baynes RD, Bothwell TH, Flax H, McDonald TP, Atkinson P, Chetty N, Bezwoda WR, Mendelow BV. Reactive thrombocytosis in pulmonary tuberculosis. J ClinPathol. 1987 Jun;40(6):676-9.
13. Schlossberg D. Tuberculosis and NonTuberculous Mycobacterial Infection. 4th ed. Philadelphia: Saunders; 2000.
14. Shah AR, Desai KN, Maru AM. Evaluation of hematological parameters in pulmonary tuberculosis patients. J Family Med Prime Care 2022; 11:4424-25.
15. Batool Y, Pervaiz G, Arooj A, Fatima S. Hematological manifestations in patients newly diagnosed with pulmonary tuberculosis. Park J Med Sci 2022; 38(7) : 1968-72.
16. Ufelle SA, Onyekwelu KC, Achukwu PU, Ndubisi AC, Ezeh RC, Nwokolo LN. Hematological profiles of patients with extra-pulmonary tuberculosis. Clinical Medicine Research 2020;9(1) : 20-24.
17. Patel GR, Sagar AK. Hematological Abnormalities in patients with newly diagnosed tuberculosis: an analysis among patients referred to clinical hematology department at a large tertiary center from western india. International Journal of Current Medical and Applied Sciences 2022; 35(2):18-25.
18. Banerjee M, Chaudhary BL, Shukla S. Hematological profile among pulmonary tuberculosis patients in tertiary care hospital. Int J Bioassays. 2015;4(05):3900-2.