Intracardiac Thrombus and Pulmonary Embolism in Rapidly Progressive Cavitating Pneumonia: A Thrombotic Tale of Klebsiella pneumoniae

INTRODUCTION

Infections caused by Gram-negative organisms may predispose patients to a prothrombotic state. The lipopolysaccharide (LPS) component of Gram-negative organisms performs central part in triggering endothelial dysfunction, systemic inflammation, and activation of the coagulation cascade, all of which contribute to the thrombosis process and lead to a prothrombotic state.^[1] The extent of thrombosis depends on the severity of infection and extent of inflammatory response.^[2] Klebsiella pneumoniae is the leading cause of Gram-negative infections.^[3] K. pneumoniae infection has been associated with various thrombotic events such as pulmonary embolism, cerebral infarction, renal vein thrombosis, and deep vein thrombosis (DVT), apart from pulmonary manifestations.^[4,5] Intracardiac thrombus formation in the absence of the left ventricular (LV) systolic dysfunction is uncommon in patients with K. pneumoniae. We present a rare instance where rapidly progressive cavitating pneumonia due to K. pneumoniae is complicated by both pulmonary embolism and LV thrombus and discuss its diagnostic and therapeutic challenges.

CASE REPORT

A 36-y/o woman without any known health issues came to our hospital complaining of chest pain and shortness of breath during activity for 3 days. She also had a low-grade fever, cough, and produced a small amount of sputum over the past 2 days. She had no history of pulmonary tuberculosis. On investigation, her temperature was normal, pulse was slightly elevated at 108 beats/min, blood pressure has been 120/70 mmHg, and her oxygen saturation came out 96% while breathing room air. Heart examination showed no abnormalities. Listening to her lungs, normal breath sounds were heard along with some crackling sounds in the left chest area. Blood tests showed a hemoglobin level of 15.2g/dL and hematocrit of 42%. The white blood cell count was elevated at 19,200 cells/mm³, while the platelet count was 233,000 cells/mm³. In addition, the erythrocyte sedimentation rate (ESR) was high, measuring 90 mm after 1 hour. Her random blood sugar was 180 mg/dL. Tests for viral infections came back negative. On the day of admission, the chest X-ray was normal. The ECG exhibited right-axis deviation, sinus tachycardia, as well as signs of the right ventricular strain [Figure 1]. A two-dimensional transthoracic echocardiogram discovered mild enlargement of the right atrium and right ventricle with the right ventricular dysfunction tricuspid annular plane systolic excursion (TAPSE 14 mm) and a tricuspid regurgitation pressure gradient of 40 mmHg. The left ventricle had normal function with an ejection fraction of 58%, but a polypoid clot measuring 1.8 × 1.4 cm was attached to LV apex [Figure 2]. Computed tomography (CT) pulmonary angiography showed a near-total blockage in the left main pulmonary artery extending into upper lingula and lower lobar arteries, along with segmental and sub-segmental arteries [Figure 3]. Chest CT scan revealed a small, thin-walled cavity in the upper part of the left lung, surrounded by areas of hazy opacity [Figure 4a and b]. Ultrasound of abdomen and Doppler studies of both legs were normal. Blood, sputum, and urine samples have been collected for culture. The patient was started on a heparin infusion along with empirical treatment using ceftriaxone. Despite this, her shortness of breath and chest pain worsened, and she experienced two episodes of coughing up blood on the 3^rd day. As a result, heparin was discontinued, and blood clotting tests (APTT and international normalized ratio/prothrombin time [PT/INR]) were ordered. A repeat chest X-ray revealed thick-walled cavity with air-fluid levels in the upper and middle areas of the lung [Figure 5]. Her white blood cell count and ESR continued to rise, with ESR reaching 122 mm after 1 h. A follow-up CT scan demonstrated thick, irregular cavitating lung consolidation with air-fluid levels and surrounding hazy opacities. Tests for tuberculosis, including sputum for acid-fast bacilli and nucleic acid testing, were negative. However, sputum culture grew K. pneumoniae, sensitive to tazobactam, piperacillin, as well as amikacin, so her antibiotics were adjusted accordingly. After 48 h without further bleeding, she was started on oral apixaban. Her symptoms gradually improved. A repeat echocardiogram showed that the clot in the left ventricle had disappeared, and the right ventricular function had improved (TAPSE 18 mm). Tests for underlying clotting disorders were negative. The patient was discharged on apixaban and advised to follow-up regularly. Three months later, imaging showed complete resolution of the lung cavity [Figure 6]. She was able to resume her daily activities and return to work.

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Figure 1:

ECG showing right ventricular strain pattern. (ECG: Electrocardiogram)

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Figure 2:

Two-dimensional transthoracic echocardiography showing left ventricular clot. (Blue arrow: Clot in the apex of left ventricle).

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Figure 3:

Computed tomography Pulmonary angiography reveals a thrombus (blue arrow) in the right pulmonary artery.

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Figure 4:

(a) Computed tomography of thorax showing cavity in upper lobe of left lung. (b) Repeat computed tomography of thorax showing progressive large cavity with air fluid level in left lung.

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Figure 5:

Chest X-ray showing left upper lobe cavity with air fluid level.

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Figure 6:

Chest X-ray showing radiological clearance of a large cavity.

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DISCUSSION

K. pneumoniae, Gram-negative bacteria, is associated with a hypercoagulable state, leading to thrombotic complications such as pulmonary embolism, DVT, cerebral infarctions, and renal vein thrombosis. The pathogenesis of such a complication is multifactorial and commonly linked with the inflammatory process evoked by the LPS moiety of the pathogen, which initiates a cascade of cytokine release, endothelial damage, and enhanced platelet aggregation. Investigations demonstrated that sepsis-induced inflammation can significantly harm the fibrinolytic system, resulting in a prothrombotic environment. These thrombotic events frequently occur in multiple vascular territories, leading to systemic embolism and end-organ damage.^[1,2]

Thrombotic events caused by K. pneumoniae are not limited to pulmonary or systemic venous territory. Fadeyi et al. designated case of 58-y/o female presenting with disseminated thrombosis, septic emboli, and multi-organ abscesses in the context of K. pneumoniae infection.^[6] Patient has been successfully treated with combination of suitable antibiotics as well as anticoagulation, highlighting organism’s ability to induce systemic thrombo-inflammatory reactions beyond the respiratory tract.

Zhou et al. reported cerebral venous sinus thrombosis in a patient with Klebsiella-associated liver abscess, providing further evidence that the organism causes thrombosis in unusual vascular areas through mechanisms such as bacteremia, endotoxemia, and immune-mediated endothelial damage.^[7]

In patients with K. pneumoniae infection, septic emboli can form from infected cardiac or vascular structures such as the left ventricle. In a research by Ko et al., (2002) patients having K. pneumoniae bacteremia had a higher risk of pulmonary embolism than patients with other gram-negative infections.^[8] Similarly, septic embolism has been reported in patients with infective endocarditis or intracardiac thrombosis.

Intracardiac thrombus formation is typically associated with reduced ventricular contractility, such as myocardial infarction or dilated cardiomyopathy. However, exceptions have been reported where thrombus formation occurs despite normal LV function due to systemic or hematologic abnormalities that predispose to a hypercoagulable state. Hypercoagulable state has been linked to intra-cardiac thrombus formation even in absence of severe LV systolic dysfunction.^[9-11]

Schmaier and Denenberg outlined patient having polycystic disease of several organs who had a case of LV thrombus with normal LV function, which was ascribed to hyperaggregable platelets, suggesting that platelet dysfunction or systemic hypercoagulability by itself might be sufficient for intracardiac clot formation in the absence of structural heart disease.^[9]

Toto et al. defined rapidly developing LV apical thrombus in myeloproliferative disorder patient.^[10] Their article showed that myeloproliferative neoplasms can cause thrombus formation due to increased blood viscosity and platelet activation, even in the absence of underlying LV dysfunction.

Kumar et al. showed case of intracardiac thrombus in community-acquired K. pneumoniae in a 55-y/o woman with transient LV systolic dysfunction, which resolved with antibiotics and anticoagulation.^[11] This case lends support to the hypothesis that septic myocardial stunning can occur in severe infections as a result of systemic inflammatory response syndrome and that this can predispose to clots even when there is no overt systolic dysfunction present.

The patient came in with sudden breathing difficulties caused by a fast-growing, cavitating K. pneumoniae, along with blood clots in lungs and heart. These clotting problems were likely linked to a prothrombotic condition triggered by sepsis from K. pneumoniae infection. Anticoagulation therapy is critical in the treatment of thromboembolic complications, but its use must be balanced against the risks of hemorrhage, particularly in patients with active infection and cavitating pneumonia. In our case, patient has been initially treated with intravenous heparin, followed by oral apixaban 48 h later, as no new episodes of hemoptysis occurred. A multidisciplinary team, including infectious disease specialists, cardiologists, and intensivists, is typically best suited to managing sepsis-associated thrombosis. Prompt initiation of appropriate antibiotics, along with anticoagulation, will significantly improve the outcome in such patients, as evidenced in the present patient, who had complete recovery with resolution of the thromboembolic syndromes and pneumonia.

CONCLUSION

Cases of K. pneumoniae causing rapidly progressing large cavitating pneumonia accompanied by sepsis-related thrombotic events, like LV thrombus in an otherwise healthy heart and acute pulmonary embolism, are rarely described in the literature. The present case demonstrates challenges in managing patients who develop severe lung infections and pulmonary embolism with hemoptysis simultaneously. It also points to the connection between Gram-negative bacterium, K. pneumoniae, and an inflammatory state that promotes clotting and leads to complications outside the lungs. Patients diagnosed with K. pneumoniae, especially those whose condition worsens, should be carefully evaluated for clotting complications related to sepsis and treated promptly with the right antibiotics, anticoagulants, and supportive care.