|Year : 2021 | Volume
| Issue : 1 | Page : 26-30
To study the clinico-radiological profile of patients of pulmonary tuberculosis with deep vein thrombosis
Deepak Sharma1, Prabhpreet Sethi1, Anita Yadav2
1 Department of Tuberculosis and Respiratory Diseases, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India
2 Department of Radiology, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India
|Date of Submission||03-Nov-2020|
|Date of Acceptance||30-Nov-2020|
|Date of Web Publication||28-Feb-2021|
Department of Tuberculosis and Respiratory Diseases, National Institute of Tuberculosis and Respiratory Diseases, Sri Aurobindo Marg, New Delhi - 110 030
Source of Support: None, Conflict of Interest: None
Objective: The objective of the study was to study the clinico-radiological profile of patients of pulmonary tuberculosis (TB) with deep vein thrombosis (DVT). Method: This is a prospective cross-sectional observational study from September 2017 to March 2019 on diagnosed patients of pulmonary TB who attended the outpatient department or presented with signs and symptoms of DVT. Results: A total of forty patients were included, out of them 57.5% were males. Nearly 45% of the patients belonged to the upper lower class. Nearly 77.5% of cases were undernourished and did not have any comorbid conditions. Sputum smear was reported positive in 92.5% of cases. Bilateral disease was seen in 95% of cases. Far advanced chest X-ray involvement was seen in 72.5% of cases. Newly diagnosed cases of TB were 87.5%. Maximum thrombus formation was seen 97.5% in superficial femoral vein and 92.5% in the common femoral and popliteal vein. Hypoxia was reported in 62.5% of cases. Interval between diagnosis of TB and the development of DVT was 2–3 weeks in a maximum of 35% of cases. Conclusion: The clinical profile of TB with DVT shows a male predominance with upper lower class more prone to develop disease and its complications. Poor physical built is seen in the majority of patients with TB and DVT. New cases of TB are still on rise. Single comorbid condition cannot define the increased risk of DVT in TB. Superficial venous system of lower limb is more prone to develop thrombus. Time interval between TB and development of DVT is variable and cannot be predicted.
Keywords: Deep vein thrombosis, hypoxia, tuberculosis
|How to cite this article:|
Sharma D, Sethi P, Yadav A. To study the clinico-radiological profile of patients of pulmonary tuberculosis with deep vein thrombosis. Int J Mycobacteriol 2021;10:26-30
|How to cite this URL:|
Sharma D, Sethi P, Yadav A. To study the clinico-radiological profile of patients of pulmonary tuberculosis with deep vein thrombosis. Int J Mycobacteriol [serial online] 2021 [cited 2021 Oct 18];10:26-30. Available from: https://www.ijmyco.org/text.asp?2021/10/1/26/310505
| Introduction|| |
Tuberculosis (TB) is continuously on the rise in India. The statistics continue to be nothing short of brutal. Despite the government of India's efforts to control TB, the disease continues to kill two people every 3 min or nearly 1000 daily, according to TB Control – India (www.tbcindia.org). The World Health Organization's TB report (2006) indicated that India has more new TB cases annually than any other country, while Global TB Report Card 2007 indicates that India not only retains a high burden of TB but also is at a substantial risk for developing multidrug-resistant TB on a large scale. As per the Global TB report 2018, in 2017, around 10.0 million people (range, 9.0–11.1 million) developed TB disease.
Deep vein thrombosis (DVT) is known to be associated with TB infection. DVT in TB is implicated due to release of inflammatory cytokines, decreased synthesis of anticoagulant proteins, and increased fibrinogen levels. Anti-TB drugs also predispose to a hypercoagulable state. DVT is not a rare association with pulmonary TB (PTB). Even children can have this complication, often correlating with the severity of the infection. Deep venous thrombosis has been associated with 1.5%–3.4% cases of TB. Early initiation of anti-TB treatment along with anticoagulant therapy decreases the overall morbidity and mortality associated with the disease.
TB and HIV are two risk factors, either alone or in conjunction for DVT. VTE may occur as a complication in patients with either condition or where both conditions occur together and appropriate thromboprophylaxis is recommended. Previous case reports and literature on clinic radiological correlation between TB and DVT done in the past are sparse.,
A number of studies have explored the association between TB and VTE, but these studies are based on case reports or small case series, or they have been conducted in countries with both poor public sanitation and high TB incidence.,,,
Thus, we did the present study to know about the clinico-radiological correlation between TB and DVT.
| Method|| |
We conducted a prospective cross-sectional observational study for 18 months (September 2017–March 2019) on patients who were diagnosed cases of PTB and were attending National Institute of Tuberculosis and Respiratory Diseases (NITRD) outpatient department or who presented with signs and symptoms of DVT (Swollen limb/limbs) and were admitted in the wards at the National Institute of TB and Respiratory Diseases, New Delhi, after taking approval from the ethical committee of NITRD. All diagnosed cases of PTB (microbiologically confirmed as well as clinically diagnosed as per the RNTCP guidelines) on antitubercular drugs with confirmed DVT on Doppler study were included in the study after taking informed consent. Patients who were not willing to participate in the study, patients of PTB with confirmed cancer, recently undergone surgery, heterotopic ossification trauma, and patients with hypercoagulable state were excluded from the study.
Detailed history was taken, and detailed examination was done on patients included in the study. Baseline investigations were done, and two sputum samples were taken from each patient. Chest X-ray posteroanterior view was done of all patients. Ultrasonography (USG) Doppler study of the affected limb in patients with signs and symptoms of DVT was done. Descriptive statistical analysis was applied for data evaluation and interpretation. Data analysis was performed utilizing Statistical Package for the Social Sciences, IBM manufacturer, Chicago, USA, version 20.0 package and processed on Microsoft Office Excel utility. All qualitative data were processed and analyzed manually.
| Results|| |
In our study on forty patients, there were 23 (57.5%) males and 17 (42.5%) females. The age group distribution shows that 26–40 years had majority 14 (35%) patients, 10–25 years had 13 (32.50%), 41–65 years had 11 (27.50%), and >65 years had 2 (5.00%) patients. According to socioeconomic status, upper lower class had maximum 18 (45%) patients, lower class had 16 (40%), and lower middle class had 2 (5%) patients. None of the patient was from upper class. According to the history of the patients, 26 (65%) were nonsmokers and 14 (35%) were smokers. Out of forty patients, 9 (22.5%) were diabetic and 31 (77.5%) were nondiabetic. According to body mass index (BMI), the majority 31 (77.5) were undernourished and 9 (22.5%) patients had normal BMI [Table 1].
All forty patients (100%) had cough, fever, and weight loss. Breathlessness, chest pain, and hemoptysis were seen in 29 (72.50%), 7 (17.50%), and 2 (5%) patients, respectively. Out of forty, sputum smear for AFB was positive in 37 (92.5%) patients. Bilateral and unilateral chest X-ray involvement was seen in 38 (95%) and 2 (5%) patients, respectively [Table 2].
Cavitatory lesion on chest X-ray was seen in 13 (32.5%) patients. The majority of the cases 29 (72.5%) had far advanced chest X-ray involvement, 9 (22.5%) had moderately advanced, and 2 (5%) had mild chest X-ray involvement according to chest X-ray severity [Table 2].
Among 40 patients, 23 (57.5%) received antitubercular treatment (ATT) course only once. Previously treated patients were 17 (42.5%). CAT1, CAT2, and DRTB regimen as received by 35 (87%), 3 (7.5%), 2 (5%), patients, respectively [Table 2].
In our study, pain and calf tenderness were seen in 40 (100%) patients. Erythema and warm extremities were present in 39 (98.5%) patients. Limb selling was reported in 38 (95%) cases. Prominent veins and discoloration of the limb were seen in 18 (45%) and 6 (15%) patients, respectively [Table 3].
Doppler study of leg veins shows the presence of thrombus in superficial femoral vein in 39 (97.5%), common femoral vein and popliteal vein in 37 (92.5%), and deep femoral vein in 6 (15%) cases. The posterior tibial vein had thrombus in 27 (67%) cases. Thrombus was found in 13 (32.5%) patients in external iliac vein. Formation of thrombus was seen in 2 (5%) and 4 (10%) patients in peroneal and anterior tibial vein, respectively [Table 3].
Hypoxia was present in 25 (62.5%) patients and 15 (37.5%) patients did not show any signs and symptoms of hypoxia. Bedridden duration was 11–20 days for 22 (55%), <10 days for 8 (20%), 21–30 days for 6 (15%), and >30 days for 4 (10%) patients [Table 4].
The interval between the diagnosis of TB and DVT was 2–3 weeks in majority of the patients (35%), followed by 3–4 weeks in 27.5% of patients [Figure 1].
|Figure 1: Interval between the diagnosis of pulmonary tuberculosis and deep vein thrombosis|
Click here to view
| Discussion|| |
This remains the first complete original research to determine the clinical profile of DVT in TB patients. Previously, the data contains only the case series and individual case or case reports. In this study, the age group of the study population is wide. It ranges from 10 years to >65 years with 57.5% males and 42.5% females. More than one-third of the cases fall in the age group of 26–40 years, i.e., after the second decade of life. The majority of the patients (57.5%) with a diagnosis of TB were males in our study. Only a few previous studies have been done on the adult population with TB and DVT that have a complete demographic profile. A study included 49 patients with TB, of which 31 (63%) were males and 18 (36.7%) were females. Another study had 8097 (65.8%) males and 4217 (34.2%) females enrolled in it, of which 7753 (66.5%) were males and 3905 (33.5%) were females and the males reported TB infection after the second decade of life. These studies had shown similar results with our study that TB occurs more in males.
In previous studies, small case reports on individual subjects with follow-up have been done where the single subjects are diagnosed with TB and DVT, and treatment has been given., Hence, no comparison of the demographic profile can be made with the previous case reports. Thus, we can say that occurrence of TB is more in males due to the fact that males travel more, more social contact, spending more time in setting that is more conducive for transmissions such as bars. Men also report more risk factors associated with TB as shown in some of the studies.,,
The common symptoms of patients in this study included fever, cough, and weight loss in all (100%) patients. For DVT, common symptoms were pain and calf tenderness in all (100%) patients, whereas limb swelling was seen in 39 (98.5%). Previous studies suggest that patients presented with common symptoms of cough, fever, weight loss, limb swelling and pain in limbs, and calf tenderness in different age groups.,, The results of the previous studies are similar to our study with respect to the signs and symptoms. Therefore, we can say that majority of patients who present with TB and DVT show similar presenting features irrespective of the age group.
The number of patients who developed hypoxia in this study were 25 (62.5%) and 22 (55%) were bedridden for 11–20 days. In previous studies, TB patients have shown hypoxia. Other small case studies have shown hypoxia present in heavy smoker individual patients of TB with PO2 of 89 mmHg. According to one study, 12% of the patients with TB and DVT were bedridden. A small case study shows that TB patient developing DVT causes immobilization in patient due to swelling of limbs, increasing the propensity of bedridden.
In diagnosis of DVT, USG is most commonly used imaging modality. Its sensitivity ranges from 37% to 88%. Tests using isotope or radiolabel radioactive fibrinogen leg scanning is used for the detection of DVT. This test is moderately sensitive and specific or calf and popliteal vein thrombosis but less sensitive for superficial femoral and iliac vein thrombosis. Acu Tect venogram is indicated as a test for acute venous thrombosis in the lower extremities of patients with signs and symptoms of acute venous thrombosis. This test can be done in TB patients with DVT. Another investigation is Doppler augmented ultrasound and impedance plethysmography (IPG), which is sensitive to occlusive thrombi but nonsensitive to calf thrombi.
In this study, we used the most widely utilized and available noninvasive test for DVT, that is, Doppler USG, which has become the most dominant test since 1980s and has replaced IPG. B mode of USG Doppler is highly sensitive in picking up thrombus by identifying blood vessel, visualizing the thrombus, and testing the compressibility along with the flow of direction. These are color flow imaging techniques that identify the blood flow around partially occlusive thrombus. Sensitivity of compression USG is reported as high as 95% in the previous study.
In previous studies, the interval between TB and DVT is variable between 1 and 4 weeks and with maximum patients developing DVT within 3rd to 4th week of diagnosis of TB. Some patients developed DVT at the diagnosis of TB, while others developed S/S of DVT while on ATT treatment.,,, Our study results are comparable with the previous studies.
Hence, we can say that time interval between the diagnosis of TB and the development of DVT varies from 2 to 4 weeks, but this also implies that clinicians should keep in mind the possibility of DVT at the time of diagnosis of TB. We recommend based on this study that whenever a new patient of TB is diagnosed, screening for DVT using USG Doppler should be done at that time only irrespective of the presence of the signs and symptoms of DVT.
Limitation of this study is that coagulation profile of the patients was not taken into account. The study has strength in depicting the clinical profile of a large number of patients of TB with DVT. Out study helps in increasing the knowledge and awareness about this profile of patients and may help guide the future investigations and treatment for such patients.
| Conclusion|| |
The study shows that TB with DVT is becoming common with male predominance. The lower class of patients is more prone to develop TB and its complications. Superficial venous system of lower limb is more prone to develop thrombus in TB patients. The time interval between TB and the development of DVT is long (2–4 weeks), and efforts should be made to screen all TB patients with USG Doppler for DVT irrespective of the presence or absence of signs and symptoms of DVT for an early detection and management.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bagchi S. Tuberculosis rates skyrocketing in India. CMAJ 2007;176:1814.
Gupta A, Mrigpuri P, Faye A, Bandyopadhyay D, Singla R. Pulmonary tuberculosis An emerging risk factor for venous thromboembolism: A case series and review of literature. Lung India 2017;34:65-9.
] [Full text]
Awolesi D, Naidoo M, Cassimjee MH. The profile and frequency of known risk factors or comorbidities for deep vein thrombosis in an urban district hospital in KwaZulu-Natal. South Afr J HIV Med 2016;17:425.
Goncalves IM, Alves DC, Carvalho A, Brito M do C, Calvario F, Duarte R. Tuberculosis and Venous Thromboembolism: A case series. Cases J 2009;2:9333.
Dentan C, Epaulard O, Seynaeve D, Genty C, Bosson JL. Active tuberculosis and venous thromboembolism: association according to international classification of diseases, Ninth revision hospital discharge diagnosis codes. Clin Infect Dis 2014;58:495-501.
Sarkar S, Saha K, Maikap MK, Jash D. Deep vein thrombosis: A rare association with tuberculosis. J Med 2012;13:106-8.
Azdaki N, Moezi S, Farzad M. Pulmonary tuberculosis: A differential diagnostic priority in unprovoked deep venous thrombosis patients with haemoptysis. Pan Afr Med J 2018;29:57.
Kechaou I, Cherif E, Ben Hassine L, Khalfallah N. Deep vein thrombosis and tuberculosis: a causative link? BMJ Case Rep 2014 May 23;2014:bcr2013200807. doi: 10.1136/bcr-2013-200807.
Kristman-Valente A, Wells EA. The role of gender in the association between child maltreatment and substance use behavior: a systematic review of longitudinal research from 1995 to 2011. Subst Use Misuse 2013;48:645-60. doi: 10.3109/10826084.2013.800115.
Jiménez-Corona ME, García-García L, DeRiemer K, Ferreyra-Reyes L, Bobadilla-del-Valle M, Cano-Arellano B, et al. Gender differentials of pulmonary tuberculosis transmission and reactivation in an endemic area. Thorax 2006;61:348-53.
Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al
. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: A systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2224-60.
Ha H, Kim KH, Park JH, Lee J-K, Heo EY, Kim JS, et al
. Thromboembolism in mycobacterium tuberculosis infection: Analysis and Literature review. Infect Chemother 2019;51:142.
Higgerson RA, Lawson KA, Christie LM, Brown AM, McArthur JA, Totapally BR, et al. Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients. Pediatr Crit Care Med 2011;12:628-34. doi: 10.1097/PCC.0b013e318207124a.
Male C, Chait P, Ginsberg JS, Hanna K, Andrew M, Halton J, et al
. Comparison of venography and ultrasound for the diagnosis of asymptomatic deep vein thrombosis in the upper body in children: results of the PARKAA study. Prophylactic Antithrombin Replacement in Kids with ALL treated with Asparaginase. Thromb Haemost 2002;87:593-8.
Hirsh J, Gallus AS. 125 I –Labelled fibrinogen scanning: Use in diagnosis of venous thrombosis. JAMA 1975;233:970-3.
Foley WD, Middleton WD, Lawson TL, Erickson S, Quiroz FA, Macrander S. Color Doppler ultrasound imaging of lower-extremity venous disease. AJR Am J Roentgenol 1989;152:371-6.
[Table 1], [Table 2], [Table 3], [Table 4]