Pulmonary tuberculosis associated with acute pulmonary embolism, pulmonary infarction and femoral deep vein thrombosis in an HIV-negative adolescent: a case report

¹Serviço de Pneumologia, Hospital Central de Maputo, Maputo, Mozambique, ²Hospital Provincial da Matola, Matola, Mozambique

^&Corresponding author
Helen Acosta Ochoa, Serviço de Pneumologia, Hospital Central de Maputo, Maputo, Mozambique

Introduction    

Tuberculosis (TB) is primarily recognized as an infectious disease, yet active TB can also produce systemic haemostatic abnormalities. Inflammation, endothelial and platelet activation, increased fibrinogen, and reduction of natural anticoagulant activity can collectively generate a hypercoagulable state [1-3]. A systematic review and meta-analysis of nine studies including 16,190 patients with active TB reported higher odds of venous thromboembolism (VTE), including pulmonary embolism (PE), among patients with active TB [1]. Thromboembolic complications have been reported in adolescents, but remain unusual and may be overlooked when respiratory deterioration is attributed solely to pulmonary infection [4]. We describe microbiologically confirmed pulmonary TB presenting concurrently with objectively confirmed common femoral deep vein thrombosis (DVT), acute segmental PE and pulmonary infarction in a 17-year-old HIV-negative adolescent without classical thrombotic risk factors.

Patient and observation     

Patient information: a 17-year-old female with no known pathological personal history presented with progressive dyspnoea and symptoms in the left lower limb. Approximately 15 days before admission, she developed productive cough with white sputum and intermittent fever. Approximately one week before admission, she developed progressive dyspnoea together with pain, swelling and functional limitation of the left lower limb. She was HIV negative, was not using oral contraceptives, and had no identified classical thrombotic risk factors in the available clinical history. Pregnancy testing (β-hCG) was negative. A complete inherited/acquired thrombophilia study was unavailable, which limits interpretation of causality.

Clinical findings: at admission, peripheral oxygen saturation was 89-91% on room air, heart rate 122 beats/min, respiratory rate 27 breaths/min and blood pressure 110/70 mmHg. The lower limbs were asymmetric. The left lower limb was oedematous, warmer locally and painful along the venous trajectory, with associated functional limitation. The patient remained haemodynamically stable.

Timeline: approximately 15 days before admission, the patient developed productive cough with white sputum and intermittent fever. Approximately seven days before admission, she developed progressive dyspnoea associated with pain, swelling and functional limitation of the left lower limb. On admission, SpO₂ was 89-91% on room air, heart rate 122 beats/min, respiratory rate 27 breaths/min and blood pressure 110/70 mmHg. Initial investigations showed haemoglobin 5.5 g/dL, platelets 564,000/µL, ESR 103 mm/h and D-dimer 2,800 ng/mL FEU; HIV, β-hCG and ANA tests were negative. Sputum Xpert MTB/RIF detected Mycobacterium tuberculosis without rifampicin resistance. Left lower-limb Doppler ultrasonography demonstrated acute common femoral DVT with reduced venous flow and preserved arterial flow. CT pulmonary angiography demonstrated acute right segmental PE, right middle-lobe pulmonary infarction and a granulomatous/tree-in-bud parenchymal pattern compatible with active TB. During hospitalization, she received oxygen, enoxaparin 60 mg subcutaneously every 12 hours for one week, two months of H/R/Z/E followed by four months of H/R with pyridoxine, two units of packed red cells, folic acid, and iron. On day 7, she was discharged without an oxygen requirement or clinical respiratory failure and with clinical improvement. At approximately two months, she was clinically well; planned etiological markers and control Doppler ultrasonography were not performed because of resource limitations. At six months, she was asymptomatic with good functional capacity; echocardiography was normal with LVEF approximately 63%; she had completed the TB regimen (2 months 4DFC + 4 months 2DFC) and six months of anticoagulation; and no recurrent VTE was documented.

Diagnostic assessment: laboratory investigations showed severe anaemia (haemoglobin 5.5 g/dL), thrombocytosis (564,000/µL), ESR 103 mm/h, and D-dimer 2,800 ng/mL FEU. Sputum Xpert MTB/RIF detected Mycobacterium tuberculosis, with no rifampicin resistance detected. HIV and β-hCG testing were negative; ANA was negative. Electrocardiography showed tachycardia and findings interpreted as suggestive of acute right-heart strain. Doppler ultrasonography of the left lower limb demonstrated acute thrombosis of the common femoral vein, with reduced venous flow and preserved arterial flow (Figure 1). CT pulmonary angiography demonstrated a filling defect in a right segmental pulmonary arterial branch, consistent with acute PE, together with a right middle-lobe pulmonary infarction. The same examination showed granulomatous/tree-in-bud parenchymal abnormalities compatible with active pulmonary TB (Figure 2). The final working diagnoses were: microbiologically confirmed active pulmonary TB; acute common femoral DVT; acute right segmental PE with pulmonary infarction; hypoxaemia at presentation; and severe anaemia. Given the patient's age, alternative inherited or acquired thrombophilic disorders remained relevant differential aetiologies. A complete thrombophilia panel was unavailable, so TB is interpreted as a plausible precipitating factor rather than a proven sole cause.

Therapeutic intervention: initial management included oxygen therapy and therapeutic enoxaparin 60 mg subcutaneously every 12 hours for one week. After microbiological confirmation of TB, first-line antituberculosis treatment was administered as two months of the four-drug combination isoniazid, rifampicin, pyrazinamide and ethambutol (4DFC), followed by four months of isoniazid and rifampicin (2DFC), with pyridoxine. Because of severe anaemia, the patient received two units of packed red cells, together with folic acid and iron. Enoxaparin was administered for one week, after which rivaroxaban 20 mg once daily was used for maintenance anticoagulation. Anticoagulation was continued for a total of six months.

Follow-up and outcomes: clinical evolution was favourable. On hospital day 7, the patient was discharged without need for supplemental oxygen and with correction/improvement of the severe anaemia and marked improvement of the left-limb manifestations. Follow-up was coordinated through pneumology, cardiology and other involved services. At approximately two months, planned etiological markers and repeat lower-limb Doppler were not completed because of resource limitations. By six months, the patient was asymptomatic with good functional capacity. Echocardiography was normal with a left ventricular ejection fraction of approximately 63%. Antituberculosis treatment and anticoagulation had been completed, and no recurrent thromboembolic event was documented.

Patient perspective: “It was a major experience. I thought I would never recover, but thanks to God and the doctors, I am healthy and continuing my secondary education. Thank you all.”

Informed consent: written informed consent for publication of this case report and accompanying anonymized clinical images was obtained from the patient and her legal representative. The signed consent form will be retained and provided to the journal if requested.

Discussion     

The central clinical lesson is that active pulmonary TB and acute VTE can coexist in an adolescent, and that respiratory deterioration in TB should not automatically be attributed to infection alone. In this patient, unilateral common femoral DVT provided an objective venous source while CT pulmonary angiography simultaneously demonstrated segmental PE and pulmonary infarction. The association is biologically plausible. Active pulmonary TB has been associated with increased coagulation activation and fibrinogen, impaired endogenous anticoagulant mechanisms, endothelial dysfunction and platelet activation [2,3,5]. In the meta-analysis by Danwang et al., active TB was associated with increased odds of VTE (OR 2.90, 95% CI 2.30–3.67) and PE (OR 3.58, 95% CI 2.54–5.05) [1]. Our patient also had marked systemic inflammation (ESR 103 mm/h) and thrombocytosis, findings consistent with an inflammatory/prothrombotic milieu, although neither establishes causality. Age makes the presentation particularly educational. Pediatric and adolescent thromboembolic complications of TB have been reported, including pulmonary thromboembolism in a 14-year-old patient, but they remain uncommon [4]. Other reports in young patients similarly illustrate that TB-associated thrombosis may occur with or without additional thrombophilic factors [6,7]. In the present case, HIV, pregnancy and oral contraceptive exposure were absent, but the inability to perform a complete thrombophilia study prevents exclusion of an underlying inherited or acquired predisposition. Accordingly, the manuscript does not claim that TB was the sole cause; rather, active TB is considered a plausible precipitating factor.

A second lesson concerns treatment in a resource-limited African setting. Rifampicin creates clinically important drug-interaction problems with oral anticoagulants. Published pharmacokinetic guidance indicates that rivaroxaban should generally be avoided with strong P-glycoprotein/CYP3A4 inducers such as rifampicin [8]. In this case, however, prolonged low-molecular-weight heparin was not feasible outside hospital and reliable INR monitoring for warfarin was unavailable. The choice of rivaroxaban was therefore a pragmatic, explicitly acknowledged compromise. Reporting this limitation transparently is important because the favourable outcome of one patient does not establish the safety or efficacy of this combination. The strengths of the case are microbiological confirmation of pulmonary TB, objective Doppler confirmation of common femoral DVT, CT angiographic confirmation of PE and pulmonary infarction, and documented medium-term clinical outcome. Important limitations are the absence of a complete thrombophilia evaluation and lack of a control Doppler at two months because of resource constraints.

Conclusion     

Active pulmonary tuberculosis can coexist with clinically important venous thromboembolism even in an HIV-negative adolescent without classical thrombotic risk factors. Disproportionate dyspnoea, hypoxaemia, persistent tachycardia or unilateral limb swelling in a patient with active TB should prompt investigation for DVT and PE. This case also illustrates the therapeutic difficulties created by rifampicin-anticoagulant interactions when monitoring and outpatient parenteral treatment are limited. Early recognition and simultaneous treatment of TB and thromboembolism were followed by a favourable six-month outcome in this patient.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Helen Acosta Ochoa: clinical case conception, data acquisition and interpretation, manuscript drafting and critical revision. Epifânio Mahagaja: clinical data contribution, interpretation and critical revision. Salma Amade: clinical data contribution, interpretation and critical revision. All authors have read, revised, and approved the final version of this manuscript.

Acknowledgements     

The authors acknowledge the multidisciplinary teams involved in the patient's care.

Figures     

Figure 1: Doppler ultrasonography of the left lower limb showing acute thrombosis of the common femoral vein, with reduced venous flow and preserved arterial flow

Figure 2: CT pulmonary angiography demonstrating a right segmental pulmonary arterial filling defect consistent with acute pulmonary embolism, associated right middle-lobe pulmonary infarction, and parenchymal tree-in-bud/granulomatous abnormalities compatible with active pulmonary tuberculosis

References