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ORIGINAL ARTICLE
Year : 2018  |  Volume : 67  |  Issue : 1  |  Page : 62-67

Assessment of the prevalence of pulmonary embolism in patients with severe pulmonary tuberculosis


Department of Chest Diseases, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission07-Nov-2017
Date of Acceptance10-Nov-2017
Date of Web Publication21-Mar-2018

Correspondence Address:
Hany Shaarawy
Department of Chest Diseases, Faculty of Medicine, Alexandria University, Alexandria
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejcdt.ejcdt_12_17

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  Abstract 


Background Tuberculosis (TB) is an infectious disease of public health concern. Many reports pointed to the association between TB and thromboembolic diseases. The aim of the present study is to assess the prevalence of pulmonary embolism in patients with severe pulmonary TB.
Patients and methods The study was done on 50 (35 males and 15 females) patients with severe pulmonary TB, and all patients were proved to have pulmonary TB by sputum or BAL examination and culture. In all patients, causes of hypercoagulability state were excluded, and computed tomography (CT) pulmonary angiography was done to search for evidence of pulmonary embolism.
Results Eight of 50 (16%) patients had evidence of pulmonary embolism, six (12%) patients had pulmonary embolism on the segmental and subsegmental level, and two (4%) patients had pulmonary embolism in the main pulmonary artery branches. The diagnosis of pulmonary embolism was done only by CT pulmonary angiography, as clinical and chest radiography signs were masked by those for pulmonary TB. Patients with evidence of pulmonary embolism were more hypoxic and had higher levels of D-dimer, but the difference was not statistically significant.
Conclusion Pulmonary embolism should be searched for in patients with severe pulmonary TB. CT pulmonary angiography is the standard method for diagnosis and can be performed in those patients who are more hypoxemic. Prophylactic anticoagulation management can be justified in these patients. Larger studies are needed to define the risk factors in patients with severe pulmonary TB who are at an increased risk of developing pulmonary embolism.

Keywords: computed tomography pulmonary angiography, pulmonary embolism, pulmonary tuberculosis


How to cite this article:
Shaarawy H, El-Sayed Mohamed E. Assessment of the prevalence of pulmonary embolism in patients with severe pulmonary tuberculosis. Egypt J Chest Dis Tuberc 2018;67:62-7

How to cite this URL:
Shaarawy H, El-Sayed Mohamed E. Assessment of the prevalence of pulmonary embolism in patients with severe pulmonary tuberculosis. Egypt J Chest Dis Tuberc [serial online] 2018 [cited 2020 Apr 3];67:62-7. Available from: http://www.ejcdt.eg.net/text.asp?2018/67/1/62/228128


  Introduction Top


Tuberculosis (TB) remains an international public health problem worldwide, with approximately nine million cases discovered and approximately three million deaths each year [1]. In many patients, TB is associated with other serious disorders including HIV infection, alcoholism, chronic renal failure, diabetes mellitus, neoplastic diseases, and drug abuse. The signs and symptoms of these diseases and their complications can easily obscure or modify those of TB and result in considerable delays in diagnosis or misdiagnosis for extended periods of time, especially in patients with HIV infection [2].

One of the comorbidities associated with TB is the hypercoagulability state, which may lead to thrombus formation anywhere in the human body. Disseminated TB may induce at the peripheral blood the activation of mononuclear cells, and the interaction of these cells activated with mycobacterial products induces increased synthesis of tumor necrosis factor α and interleukin-6 [3].

Studies evaluating the coexistence of TB and venous thromboembolism (VTE) are scant in the literature. Meanwhile, some limitations were found, as the retrospective design limited extensive investigation of the patients, including echocardiographic assessment in those with pulmonary embolism. Moreover, the actual number of VTE events in the cases most possibly exceeds those reported, partly because screening for asymptomatic VTE is not performed routinely [1].

Pulmonary embolism as a complication of pulmonary TB had received little emphasis in the literature. The first report of an association between TB and pulmonary embolism was described by Morgan [4]. Later, Ekukwe et al. [5] described a case of 52-year-old male with no risk factors for thromboembolic disease referred to their service for an in-depth clinical review for cardiomegaly and dyspnea on exertion. Echocardiography and computed tomography (CT) scans revealed dilated heart cavities and bilateral proximal pulmonary emboli, respectively, and a cavitation in the apical lobe of the right lung, bronchial aspirate, and culture revealed the presence of mycobacterium TB. There was no evidence of malignancy elsewhere. A clinical review and a lower limb ultrasound showed no evidence of deep venous thrombosis (DVT). Clinical course on anti-TB and anticoagulant therapies was remarkably favorable [5]. Clinicians need to be conscious of the risk of developing thromboembolic disease in patients treated for TB, thromboembolic disease is to search systematically in these patients to avoid the occurrence of this complication particularly in extensive and severe forms [5].

Participants

This was a prospective study that included 50 patients with newly diagnosed smear-positive severe pulmonary TB who were admitted to the Chest Disease Department. Study was done in the main Alexandria University Hospital in the period between 1 January 2016 and 31 December 2016. Written consent was taken from all patients before inclusion in the study. The study was approved by the administrative council of the Chest Diseases Department and the Ethical Committee of the Faculty of Medicine, Alexandria University.

Inclusion criteria

Patients with smear-positive pulmonary TB were included with the following criteria:
  1. Patient in respiratory distress or signs of respiratory muscle fatigue.
  2. Chest radiography showing cavitary lesion unilateral or bilateral.
  3. Chest radiography showing bilateral extensive lesion.
  4. Patients with military TB.
  5. Derangement in arterial blood gases (hypoxemia needing oxygen supplement or hypercapnia with respiratory acidosis).


Exclusion criteria

The following exclusion criteria were applied:
  1. Negative smear cases.
  2. Mild cases of smear positive pulmonary TB.
  3. Patient who are proved to have other cause for hypercoagulability.
  4. Patients with chronic respiratory or cardiac diseases.
  5. Patients with malignant tumors.



  Methods Top


All patients were subjected to the followings:
  1. History taking.
  2. Physical examination.
  3. Routine laboratory investigations.
  4. Arterial blood gases.
  5. D-dimer test (cutoff point of 500 mg/l) [6].
  6. Chest radiography.
  7. CT pulmonary angiography [7].
  8. Investigations to exclude hypercoagulability state included the following [8]:
    1. Whole blood coagulation profile.
    2. Tests for collagenic vascular diseases.
    3. Tests for vasculitis.
    4. Anticardiolipin antibodies.


Statistical analysis

All statistical analyses were conducted using the software package SPSS 20.0 for Windows (SPSS Inc., Chicago, Illinois, USA). All data are tabulated and presented as mean±SD. Independent t-test was used to compare between patient with pulmonary embolism and those without pulmonary embolism. Significant results were detected at P value of less than 0.05.


  Results Top


Fifty patients with smear-positive pulmonary TB were included in the study, with 35 males and 15 females. According to the results of the CT angiography and presence of pulmonary embolism, the patients were subdivided into two groups:
  • Group 1: 42 patients without pulmonary embolism.
  • Group 2: eight patients with proved presence of pulmonary embolism by CT pulmonary angiography.


The mean age of the patients in group 1 was 28.1±13.7 years, whereas the mean age of patients in group 2 was 27.6±14.1 years (P>0.05). The mean body weight in group 1 at presentation was 76.2±8.1 kg, whereas the mean body weight in group 2 was 74.8±9.5 kg (P>0.05). Smoking history was positive in 26 patients in group 1, whereas it was positive in four patients in group 2. No history of addiction was detected in all patients in both groups. HIV was negative in all cases. All patients of both groups had no history of chronic cardiac or respiratory disease ([Table 1]).
Table 1 Epidemiologic characteristics of the patients

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Regarding the clinical characteristics of the patients, all patients of both groups had cough, dyspnea, and sputum production at presentation; six patients in group 2 and only one patient in group 1 had hemoptysis, with statistically significant difference; fever and night sweating were present in 16 patients in group 1 and in four patient in group 2 (P>0.05); tachycardia was present in 25 patients in group 1 and in five patients in group 2 (P>0.05); and lastly, pleuritic chest pain was present in seven patients in group 1 and in three patients in group 2 (P>0.05) ([Table 2]).
Table 2 Clinical characteristics of the patients

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Regarding the laboratory criteria of the patients, all patients in group 1 and two patients in group 2 had anemia (hemoglobin level was 7.9±2.3 g/dl in group 1 and 8±2.13 g/dl in group 2, P>0.05); mean alanine aminotransferase level in group 1 was 37.4±11.6 and in group 2 was 38.5±10.8 (P>0.05); mean aspartate transaminase level in group 1 was 39.8±9.2 and in group 2 was 40.1±7.6 (P>0.05); mean oxygen saturation at the time of diagnosis was significantly lower in group 2 than in group 1 (87.2±1.2% in group 2 and 90.8±3.6% in group 1, with P=0.03); and lastly, the mean D-dimer level at the time of diagnosis was 486.8±105.3 in group 1 and 489.2±103.8 in group 2, with no statistical significance ([Table 3]).
Table 3 Laboratory criteria of the patients

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Regarding the radiologic characteristics of the patients, chest radiography showed cavitary lesion in 14 (33%) patients in group 1 and six (75%) patients in group 2; bilateral infiltrates and reticulonodular pattern was found in 13 (31%) patients in group 1 and in three (38%) patients in group 2; multilobar consolidation was found in 12 (29%) patients in group 1 and in two (25%) patients in group 2; and lastly, pleural effusion was detected in four (9%) patients in group 1 whereas it was not detected in group 2 (in combination to other signs in the chest radiography). Signs of pulmonary embolism in chest radiography were very difficult to be detected because of radiologic signs of TB infection ([Table 4]).
Table 4 Radiologic characteristics of the patients

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In the present study, eight (16%) cases of pulmonary embolism were discovered of the 50 patients included. Clinical diagnosis, laboratory criteria, or chest radiography were not of much help in diagnosis because of clinical and radiologic signs of TB. Hemoptysis was found more in patients with pulmonary embolism, but this cannot be relied upon as a distinguishing sign. Moreover, patients with pulmonary embolism were more hypoxemic at the time of admission, but there is no cutoff point to differentiate whether the patient will have pulmonary embolism or not, and patients with TB without pulmonary embolism were also hypoxemic in relation to normal population. There was no significant difference between the two groups in D-dimer value, which is a good negative test to exclude pulmonary embolism, as it may be false positive because of active infection [9]. It seems that the burden of diagnosis of pulmonary embolism needs high index of suspicion and proceeding directly to CT pulmonary angiography when needed ([Figure 1] and [Figure 2]).
Figure 1 (a, b) Mediastinal window (a) of patient no. 6 with pulmonary embolism in the left main branch of the pulmonary artery with the lung window (b) showing bilateral infiltrate owing to tuberculosis.

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Figure 2 (a, b) Mediastinal window of patient no. 12 with subsegmental pulmonary embolism and lung window showing infarct area in the right side and consolidation and infiltrate of tuberculosis in the left side.

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  Discussion Top


According to the WHO global report published in 2016, TB remains a major global public health problem with estimated 10.4 million cases newly diagnosed and estimated 1.8 million TB-related deaths in 2015 [10]. Severe TB constitutes ∼40% of cases of TB, especially in developing countries, and is associated with more complications, failure of treatment, recurrence, drug resistance, and more incidence of mortality [11],[12]. The association between TB and thromboembolic phenomenon is well established. Being able to affect all the three components of the Virchow’s triad, TB could be a significant risk factor for VTE. Circulatory stagnation can be a direct result, because of patients being bedridden owing to severe illness, loss of muscle power in severe cases, or even compression of the veins by lymph nodes can lead to thrombus formation.

TB has several mechanisms to induce hypercoagulability state including decreased level of protein C or protein S, deficiency in antithrombin Ш, association with antiphospholipid antibodies, or even hypoprothrombinemia [13],[14]. TB as an infectious disease can induces the production of many inflammatory mediators in the circulation which can lead to activation of endothelium lining of blood vessels leading to thrombus formation and can increase the formation of hepatic coagulation factors [15],[16].

Many previous reports proved this association between TB and thrombogenesis: Robson et al. [17] screened 68 patients with TB at the time of admission and followed them for 1 month for any evidence of DVT, and they found that 33 patients had DVT at the time of diagnosis and two patients developed DVT during the first month of treatment. Sharif-Kashani et al. [18] had conducted a retrospective study in one of the big centers dealing with TB in Tehran; the study was done on 3293 patients with TB who were admitted to hospital for receiving antituberculous drugs. They found that 26 patients had DVT, 13 had pulmonary embolism (PE), and seven had both DVT and PE. Other smaller reports pointing to the association between pulmonary TB and thrombogenesis demonstrated thrombus formation in patients with pulmonary TB in different parts of the body, including the hepatic veins [19], the portal veins [20], inferior vena cava [21], cerebral veins [22],[23] and the central retinal vein [24]. Kouismi et al. [25] had done a retrospective study on all patients presented to their center in Morocco with pulmonary TB, and they found 30 patients with pulmonary TB and coexisting DVT, five patients also had pulmonary embolism, and the mean time for diagnosis was 17 days after admission, with most of the patients having severe forms of pulmonary TB. Beyond the association between TB and thrombogenesis TB, the diagnosis of pulmonary embolism is very difficult from the clinical, laboratory, or chest radiography point of view, as most patients with TB have similar symptoms to those of pulmonary embolism, although the incidence of hemoptysis was higher in group 2 in the present study. Hemoptysis is a frequent symptom in patients with TB, and it cannot be a valid indicator to state whether a patient has pulmonary embolism or not. At the level of laboratory criteria, there was no significant difference between the two groups except in the oxygen saturation at the time of admission, but patients in both groups were hypoxemic in relation to normal population, and the present study could not put a cutoff point at which patient should be sent for CT pulmonary angiography. The present study had limitations especially in the number of patients. Larger studies are needed to evaluate the risk factors in patients with severe TB that can be associated with pulmonary embolism. The presence of pulmonary embolism can make the patient more hypoxemic than expected, but the study points to the importance of searching for pulmonary embolism in patients with severe pulmonary TB especially those who are more hypoxemic, and at the same time, use of prophylactic anticoagulation can be justified in patients with severe pulmonary TB especially in the initial phase of treatment.


  Conclusion Top


Pulmonary embolism should be searched for in patients with severe pulmonary TB. CT pulmonary angiography is a definite method for diagnosis and can be performed in patients who are more hypoxemic. Prophylactic anticoagulation can be justified in these patients. Larger studies are needed to define the risk factors in patients with severe pulmonary TB who are at more risk of developing pulmonary embolism.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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