The patient was treated according to the guidelines for the diagnosis and treatment of PE. Low-molecular-weight heparin calcium injection 4100 IU was administered twice daily by subcutaneous injection. Chest pain was fully alleviated after 6 days, and oral anticoagulant rivaroxaban was given after discharge. Three months later, a lung perfusion scan showed the PE in the right pulmonary artery had significantly improved, and ultrasound showed no evidence of pleural effusion (Fig. 1I–K).
PE is a general term for a group of diseases or clinical syndromes, including pulmonary thromboembolism, fat embolism syndrome, amniotic fluid embolism, and air embolism, in which emboli block one or more pulmonary arteries.[5,6] Clinical manifestations of PE are complex and diverse, and the rates of clinical misdiagnosis and missed diagnosis are high. Globally, PE is a cause of substantial acute and chronic morbidity. PE is also associated with mortality, with >30% of PE patients dying during the initial 30 days after diagnosis. As correct management of PE can reduce the mortality rate to <10%, timely and accurate diagnosis and treatment of PE are essential.
In the current study, the patient initially presented with left chest pain; she was diagnosed with double lung pneumonia and left pleural effusion. Pleural effusion may be caused by heart failure, pneumonia, cancer, and tuberculosis. In the current study, based on the patient's clinical manifestations, the chest pain was initially thought to result from parapneumonic effusion. However, administration of anti-inflammatory treatment only slightly reduced the left chest pain. New pain appeared in the right chest, which did not support a diagnosis of parapneumonic effusion; therefore, we considered occult PE.
Evidence suggests that pleural effusions occur in 19% to 61% of patients with PE. Pleural effusions secondary to PE are usually exudates. PE causes pleural effusion by increasing pulmonary capillary permeability, such that pulmonary interstitial fluid moves from the lung to the pleural space by crossing the visceral pleura. The permeability of pulmonary capillaries may be increased by the release of inflammatory mediators from clots that are rich in platelets. These inflammatory mediators include vascular endothelial growth factor (VEGF), which is among the most effective vascular permeabilizing factors known. Large amounts of VEGF are contained within platelets. Permeability may also be increased by ischemia of the pulmonary capillaries distal to the embolus; however, this effect is likely to be minimal as the bronchial circulation provides blood to these capillaries.
In the current study, we describe a patient with PE and migratory pleural effusion in which the left pleural effusion migrated to the right following antibiotic treatment. Studies in patients with unilateral pleural effusion show no relationship between the side of the pleural effusion and the side of the PE. Porcel et al analyzed 230 patients with PE and found pleural effusions in 93 patients. Of these, 61 patients had a unilateral PE, 38 patients had an ipsilateral pleural effusion, and 7 patients had a contralateral pleural effusion; in 16 patients, pleural effusion was bilateral. The authors concluded that the side of the pleural effusion did not correlate with the side of the PE, but they cautioned that conventional CTA may have low sensitivity for the detection of emboli in subsegmental pulmonary arteries; therefore, a contralateral pleural effusion may be an artifact. Indeed, emboli are often found in many segments or lobes of the lung in autopsy studies.
Pleural effusions often develop in patients with right heart failure. Most PE is accompanied by pulmonary hypertension, and thus right ventricular dysfunction. Evidence suggests that patients with pleural effusions and right heart failure have significantly elevated mean right atrial pressure, which leads to an increase in central and systemic venous pressures and the formation of pleural fluid, as parietal pleural lymphatic drainage is mechanically impeded, or because a transudate forms in the pleural space due to increased venous and hydrostatic pressures in the veins of the bronchae and chest wall. In the current study, we propose that a previously undetected PE that underwent subsequent dissolution caused the pleural effusion. In support of this, Agarwal et al indicated that pleural effusions associated with PE reach a maximum size by day 3, and further growth of the effusion or the appearance of a contralateral effusion is indicative of a recurrent embolism.
Kiris et al reported acute PE patients with pleural effusion had a significantly higher incidence of all-cause and long-term total mortality than those without pleural effusion. Unfortunately, if the amount of pleural fluid is small, pleural aspiration cannot be performed in these patients.
In the current study, the patient's D-dimer level was not remarkable. Generally, there is a dose-response relation between D-dimer level and risk for a PE. However, a PE diagnosis should not be made based on D-dimer levels alone as the test lacks specificity. The simultaneous occurrence of acute thrombosis, coagulation, and activation of fibrinolysis can elevate plasma D-dimer levels. If D-dimer levels are within the normal range, a diagnosis of PE can almost be excluded if the patient's clinical probability score for a PE is low. In patients with high D-dimer levels and a high clinical probability of PE, further tests should be used to make a definitive diagnosis.[16,17] In clinical practice, PE can be easily missed or misdiagnosed based on a normal D-dimer level. We recommend the use of CTPA to investigate the possible presence of occult PE in patients with unexplained pleural effusion and normal plasma D-dimer levels.
In the current study, as the patient had no risk factors for PE, thrombophilia may not be excluded. Thrombophilia (hypercoagulability; prothrombotic state) results from a genetic or acquired deficiency in an anticoagulant protein, clotting factor, or fibrinolytic protein. Patients with thrombophilia have a higher incidence of deep venous thrombosis and PE, collectively known as venous thromboembolism. Inherited thrombophilia is usually due to mutations in the coagulation factor V (factor V Leiden) and prothrombin (prothrombin G20210A) genes. Acquired thrombophilia may be associated with old age, obesity, inflammatory bowel disease, malignancy, smoking, a history of thrombosis, prolonged alcohol use, oral contraceptives, hormone replacement therapy, trauma, pregnancy and birth, and antiphospholipid syndrome. Nephrotic syndrome, myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, stroke, heart failure, myocardial infarction, and diabetes mellitus also cause elevated levels of coagulation factors and decreased levels of anticoagulants. We recommend that genetic testing should be considered in patients with a diagnosis of PE but an unremarkable medical history and no risk factors.
Based on the findings from the current study, we recommend that PE should be considered in patients complaining of itinerant chest pain, especially pleuritic chest pain, with unexplained migratory pleural effusion.
WL and LW carried out the data collection, literature review and drafting of the manuscript. MC contributed to the drafting of the manuscript and aided in the literature review. TX participated in the data collection and the drafting of the manuscript. PG help to draft the manuscript and revised the final version of the manuscript. All authors read and approved the final manuscript.
Data curation: Tong Xin.
Investigation: Chen Chen.
Resources: Mo Chen.
Supervision: Peng Gao.
Writing – original draft: Wei Li.
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Keywords:Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
chest pain; computed tomographic pulmonary angiography; D-dimer; pulmonary embolism; pleural effusion