Pulmonary Aspergillosis with In-Situ Pulmonary Artery Thrombosis: To Anti-Coagulate or Not?
Pulmonary aspergillosis (PA) is a spectrum of diseases caused by the fungus Aspergillus, which is ubiquitous in the environment. The clinical manifestations of PA vary depending on the host’s immune status, ranging from non-invasive conditions like allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis to invasive forms such as invasive pulmonary aspergillosis (IPA) and subacute invasive pulmonary aspergillosis (SAIA). Invasive forms of PA, particularly IPA and SAIA, are characterized by tissue invasion, including blood vessel invasion, thrombo-mycotic occlusion, and hemorrhagic infarctions. One of the severe complications associated with these invasive forms is in-situ pulmonary artery thrombosis (PAT), a potentially life-threatening condition resulting from inflammation and injury to the pulmonary artery wall.
The management of PAT is complex and often controversial, particularly when it coexists with PA. The therapeutic approach to PAT is similar to that of pulmonary thromboembolism (PTE), involving thrombolysis and anti-coagulation. However, the decision to administer anti-coagulation therapy in patients with PA and PAT is not straightforward, as it may exacerbate complications such as hemoptysis. This article presents three clinical cases that illustrate the challenges in diagnosing and managing PA with in-situ PAT, and discusses the critical factors influencing the decision to anti-coagulate.
Case 1 involved a 71-year-old man with a long history of chronic obstructive pulmonary disease (COPD) who presented with exacerbated symptoms of productive cough and dyspnea, along with edema of both lower extremities. Computed tomography pulmonary angiography (CTPA) revealed a cavity in the right lobe and dorsal segment of the lower lobe, accompanied by fibrosis and pleural thickening. Additionally, thrombosis was observed in the right main pulmonary artery, closely adjacent to the pulmonary lesion, leading to a diagnosis of in-situ PAT. The patient was started on anti-coagulation therapy. Subsequent diagnostic tests, including serum galactomannan and sputum culture, confirmed the presence of Aspergillus, leading to a diagnosis of IPA. The patient was treated with itraconazole, and his condition improved.
Case 2 involved a 75-year-old man with COPD who presented with fever and chest pain for 15 days. CT scanning revealed maculas shadows in the tip-posterior of the left upper lobe, and he was diagnosed with IPA based on microbiology findings of Aspergillus. He was treated with voriconazole. A subsequent CTPA showed a filling defect in the artery supplying the left upper lobe, consistent with in-situ PAT due to the close relationship between the artery and lung parenchyma lesions. After 10 days of anti-coagulation, the patient developed hemoptysis, and a follow-up chest CT showed rapid deterioration of the lung. Anti-coagulation was discontinued due to persistent hemoptysis, and anti-fungal therapy was continued. The patient eventually improved and was discharged on oral voriconazole.
Case 3 involved a 42-year-old woman with a history of lung tuberculosis who presented with dyspnea and hemoptysis for 5 months, with recurrence for 5 days. CTPA revealed a filling defect in the right pulmonary artery, bronchiectasis, and cavities in multiple lobes. She was initially diagnosed with PTE and treated with warfarin, but anti-coagulation was stopped due to hemoptysis. Four months later, a follow-up CTPA showed severe local pulmonary fibrosis. Five days before admission, she experienced hemoptysis again, and chest CT showed cavity formation, new nodules, and progressive massive fibrosis, suggesting SAIA. Aspergillus immunoglobulin G antibody was positive, confirming the diagnosis of SAIA. The pulmonary artery thrombotic lesion was reclassified as in-situ PAT. Intravenous itraconazole was administered, but the patient suffered fatal hemoptysis and died due to asphyxia on day 4 of admission.
These cases highlight the complexity of managing PA with in-situ PAT. The pathogenesis of PAT in PA involves Aspergillus hyphae stimulating tissue factor activity in vascular endothelial cells, leading to angioinvasion and thrombosis. Additionally, underlying pulmonary diseases, such as COPD and tuberculosis, contribute to pulmonary vascular remodeling and blood flow vortex, increasing the risk of thrombosis. CTPA is a crucial diagnostic tool for identifying PAT, particularly in distinguishing it from PTE. In PTE, thromboemboli typically migrate from the venous system of the lower extremities to the pulmonary artery, often resulting in bilateral filling defects. In contrast, in-situ thrombus formation in PAT is usually unilateral and displays mural thrombus with obtuse angles to the vessel wall.
The decision to anti-coagulate in patients with PA and PAT should be individualized, taking into account the risk of bleeding and the underlying pulmonary disease. According to the American College of Chest Physicians guidelines, bleeding risk assessment is essential before initiating anti-coagulation therapy. In Case 2, the patient had a high risk of bleeding, and anti-coagulation was discontinued after hemoptysis occurred. In contrast, anti-coagulation was beneficial in Case 1, where the patient improved with combined anti-coagulation and anti-fungal therapy. However, in Case 3, anti-coagulation exacerbated hemoptysis, leading to a fatal outcome. These cases underscore the importance of early diagnosis and timely anti-fungal therapy in managing PA with PAT. Voriconazole is the first-line therapy for invasive aspergillosis, and combination anti-fungal therapy may be necessary in immunocompromised or critically ill patients.
In summary, the differential diagnosis of PTE and PAT is crucial in patients with pulmonary parenchymal and arterial lesions. Anti-fungal therapy is essential to slow vascular invasion and prevent fatal hemoptysis. The decision to anti-coagulate should be based on a careful evaluation of the risk-benefit ratio, considering the patient’s bleeding risk and the underlying pulmonary disease. Further research and clinical studies are needed to establish clear guidelines for the management of PA with in-situ PAT.
doi.org/10.1097/CM9.0000000000000336
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