Deep vein thrombosis in patient with pulmonary tuberculosis: a rare and interesting causative link?

INTRODUCTION

Tuberculosis is one of the most devastating curable infectious diseases in our country and the world. It is caused by Mycobacterium tuberculosis, an acid fast bacilli. This disease can affect most organs in the body and lead to various sequel as a result of the organs involved.¹ Each year 8.8-12.2 million new cases are diagnosed with tuberculosis and 1.5-1.8 million deaths are caused by the same. India contributes a significant burden to these numbers of incidence and mortality and thus tuberculosis remains an important global public health problem with new complications being discovered despite its knowledge and presence since neolithic age.² The prevalence of deep vein thrombosis in patients with pulmonary tuberculosis is estimated to be around 3-4%. There is a hypothesized correlation between severe pulmonary or disseminated tuberculosis and risk of developing deep vein thrombosis. That is why it is important to sensitize all clinicians to this complication by reporting a case observed in our institution.

CASE REPORT

A 20-year-old non smoker non alcoholic male was admitted to our department for evaluation of low grade fever with evening rise in temperature, cough with copious expectoration and hemoptysis since 1 month along with diffuse non radiating dull aching pain with swelling on right lower limb since 15 days. There was no history of diabetes, stroke or cancer in the family. On physical examination, he had tachypnea and tachycardia with mild pallor. He had diffuse crepitations and rhonchi in his chest (left>right) and used his accessory muscles of respiration and was in a state of respiratory distress. Cardiovascular, and abdominal examinations were within normal limits. Routine investigations and sputum examination was done. His sputum was positive for acid fast bacilli and cultures of same were sent along with cartridge based nucleic acid amplification test. He underwent subsequent evaluation of his right lower limb complaints which was tense and tender with diffuse swelling from mid thigh to ankle. Homan test and Moses test were positive. Provisional diagnosis of deep vein thrombosis was kept. Color Doppler study of his right lower limb revealed deep vein thrombosis of external iliac vein. Patient was febrile (100 degree fahreinheit) There was no prior history of surgery, trauma or malignancy, prolonged bed rest, smoking, valvular heart disease or stroke. His investigations were sent, and they were as follows (Table 1).

Course and treatment

The overall clinical picture and radiological findings were suggestive of pulmonary tuberculosis. He was registered under DOTS as newly diagnosed sputum positive pulmonary tuberculosis and started on four drug anti tubercular treatment {rifampicin (600mg/d), isoniazid (300mg/d), pyrazinamide (1000mg/d), ethambutol (800mg/d)}. He was also treated with low-molecular-weight heparin (injection enoxaparin 60mg bid subcutaneous) for 3 days and was started on Tab. warfarin 3mg once a day with a target International Normalized Ratio (INR) of 2.0-3.0. He was initially maintained on nasal prong with 5L/hr oxygen and was slowly weaned off the same.

There was resolution of cough along with edema of the limbs and was discharged on same medications. He was followed up for 6 months. His sputum was negative for acid fast bacilli after 1 month and CBNAAT was negative. Cultures showed growth of M. tuberculosis sensitive to rifampicin and isoniazid. The patient made complete recovery of both his pulmonary and limb disease.

Chest X-ray showed bilateral ill-defined patchy shadowing right upper middle zone and non homogenous opacity at left middle lower zone with fibrosis (Figure 1). Arterial blood gas analysis showed: pH 7.47, pO2 84.9mmHg, pCO2 34.6mmHg, HCO3 25.7mmol/L and oxygen saturation 97.1.

Contrast Enhanced Chest Computerized Tomography showed multiple nodular infiltrates in bilateral lung fields with tree in bud appearance. Patchy consolidation is noted in whole of left lung with cavitatory changes and cystic bronchiectasis in left upper lobe and apical segment of left lower lobe along with consolidation of right middle lobe (Figure 2).

DISCUSSION

Mycobacterium tuberculosis is an acid fast bacilli responsible for causing tuberculosis.¹ Mortality is higher in cases diagnosed late due to increase incidence of complications and advanced stage of the disease itself. Complications of tuberculosis can be local pertaining to the organ infected such as bronchiectais, end stage lung disease, pleural effusion, constrictive pericarditis or systemic as seen in military tuberculosis which can lead to Addisonian crisis, shock on one end and disseminated intravascular coagulation at the other end.^3,4 Hematological complications of tuberculosis are known but rarely seen. These include bronchial arteritis, Rasmussen aneurysm etc.⁵ Rarely can pulmonary tuberculosis also present with deep vein thrombosis. There have been reports of deficiency of protein S and concurrent antiphospholipid antibody syndrome in patients of tuberculosis and therefore tuberculosis can be complicated by venous thromboembolism also.⁶

Deep vein thrombosis is can either be caused by inherited/hereditary factors or acquired factors. It is caused by disturbance in endothelial function or venous stasis or a hypercoagulable state.⁷ It is more commonly seen in post surgical cases or in patients on prolonged bed rest. Though medical conditions such as thrombophilias such as factor V leiden mutation and activated protein C resistance and prothrombin gene mutations have been commonly implicated for unprovoked deep vein thrombosis, these are rarely seen and most patients with medical cause of deep vein thrombosis end up with the diagnosis of malignancy induced thrombophilia.⁸ Our case did not have any recurrent venous thrombosis, any valvular heart disease nor was involved in any trauma, surgery or had any episode of prolonged bed rest. He was tested for protein C and protein S deficiency along with APLA profile, however all were normal. Unprovoked thrombosis in this case in absence of hereditary factors shows that severe pulmonary tuberculosis may be complicated by venous thromboembolism. This event can occur at the time of presentation or later in the course of the disease. This is not absolute for all cases of tuberculosis. Provisional hypothesis for this occurrence can be:^9-12

• • Tuberculosis induces an acute phase response by activation of mononuclear cells.⁷ The interaction between these activated mononuclear cells causes increase synthesis of TNF-alpha, Interleukins and proinflammatory cytokines, which can activate vascular intima and render the endothelial surface more thrombogenic and the blood more hypercoagulable thereby increasing the risk of deep vein thrombosis.
• • Tuberculosis causes anemia, reactive thrombocytosis, increase in plasma fibrinogen and factor VIII and decrease levels of antithrombin III, and protein C levels.
• • Local compression of veins by the enlarged lymph nodes.
• • Direct endothelial injury caused by Koch’s bacillus.
• • Immobility imposed by hospitalization.

These factors can lead to a hypercoagulable state that can lead to thromboembolic events. Classically, thrombosis in the lower limbs are more common in patients with pulmonary TB. However, other unusual sites have been reported in the literature in patients with pulmonary TB, namely cerebral venous sinuses or hepatic veins.¹³ In this case, the diagnosis of pulmonary tuberculosis was considered because of fever, worsening general status and cough with expectoration and sputum was positive for AFB. Good response to antitubercular therapy and culture reports consolidates this diagnosis. No other predisposing cause of DVT could be found. Anticoagulation and antitubercular therapy were started as soon as possible to improve outcome of lung as well as vascular pathology.

CONCLUSION

This clinical report emphasize that patients with severe pulmonary tuberculosis are at risk of developing thromboembolic events and deep vein thrombosis maybe one of the many atypical manifestations of pulmonary tuberculosis and the possibility of tuberculosis should be considered in those who present with unprovoked deep vein thrombosis of lower limbs.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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