Pulmonary Embolism and Pulmonary Infarction After Lung Transplantation
Clinical and Applied Thrombosis/Hemostasis 17(4) 421-424 ª The Author(s) 2011 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1076029610371474 http://cath.sagepub.com
Igor Krivokuca, MD1, Ed A. van de Graaf, MD, PhD1, Diana A. van Kessel, MD2, Jules M. M. van den Bosch, MD, PhD2, Jan C. Grutters, MD, PhD2, and Johanna M. Kwakkel-van Erp, MD1
Abstract Venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is a common occurrence in patients undergoing surgery and is a potentially fatal complication. Especially after lung transplantation, vascular complications can compromise the function of the allograft and limit survival. Typically, the risk of pulmonary infarction after PE in lung transplant recipients is high because the absence or poor development of the collateral bronchial circulation may predispose lung transplant recipients to pulmonary infarction. This article reports 2 cases of PE with associated pulmonary infarction after lung transplantation with significant morbidity. Keywords pulmonary embolism, pulmonary infarction, lung transplantation
Introduction Pulmonary embolism (PE) of thrombotic origin ranges from asymptomatic and incidentally discovered emboli to potentially fatal massive embolisms. Hospitalized and especially postoperative patients (orthopedic surgery patients after total hip and knee replacement) are particularly at risk.1 In lung transplant recipients, venous thromboembolism [VTE] (PE and deep vein thrombosis [DVT]) occurs in 8% to 27%.2 Pulmonary embolism may occur more frequently in lung transplant recipients compared to other postoperative patients and affects the allograft.3 Pulmonary infarction is generally an uncommon consequence of PE, because of the dual pulmonary circulation arising from the pulmonary and bronchial arteries.1 In lung transplant recipients, PE is often associated with infarction (37.5%) which may be due to the absent or poorly developed collateral bronchial circulation.4
Case Presentation Case 1 A 50-year-old woman, with a history of deep venous thrombosis and chronic obstructive pulmonary disease (COPD) due to severe alpha-1-antitrypsin deficiency, underwent double lung transplantation. Her posttransplantantion course was complicated by esophageal perforation, which was stented for a short period of time. She developed right empyema thoracis (pleural fluid and sputum cultures were positive for
Pseudomonas aeruginosa) and was successfully treated with chest tube drainage combined with intravenous antibiotics. The patient showed gradual clinical improvement and was discharged from the hospital 3 months after transplantation; but after just 2 days, she was readmitted because of fever. She had been receiving immunosuppressive therapy and antimicrobial prophylaxis (valganciclovir-Cytomegalovirus prophylaxis and trimethoprim/sulfamethoxazole—Pneumocystis jirovecii pneumonia [PJP] prophylaxis). On physical examination, she was hemodynamicly stable, her temperature was 37.7 C, oxygen saturation at room air was 97% and her respiratory rate was normal. Chest examination revealed bilaterally present breath sounds, slightly decreased over the right chest, especially the lower part. There were no clinical signs of deep venous thrombosis. Laboratory workup showed a leukocyte count of 25 109/L and C-reactive protein was 192 mg/L. Her chest radiogram revealed preexisting pleural effusion of the right side (Figure 1) and her chest computed tomography (CT) scan revealed the aforementioned
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Department of Respiratory Medicine, University Medical Centre Utrecht, Netherlands 2 Department of Respiratory Medicine, St. Antonius Hospital, Nieuwegein, Netherlands Corresponding Author: I. Krivokuca, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands Email:
[email protected]
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Clinical and Applied Thrombosis/Hemostasis 17(4) patient recovered very quickly. Results of bacteriological and mycological studies were negative.
Discussion
Figure 1. Chest radiograph shows a right pleural effusion and a high left diaphragm.
right-sided pleural effusion and surprisingly, in spite of prophylaxis with a low-molecular-weight heparin (dalteparine 5000 IU subcutaneously (sc) until the patient was discharged from the hospital), bilateral PE (Figure 2A) and pulmonary infarction (seen as a subpleural parenchymal opacity in Figure 2A, B). We started immediately with lifelong anticoagulation therapy with vitamin K antagonist after an initial treatment with low-molecular-weight heparin. Open embolectomy or thrombolysis were not indicated in this patient because of her hemodynamic stability. Two weeks later she developed symptoms suggestive of a bronchopleural fistula, and CT scan of the chest showed a cavity in the right lower lobe (Figure 3) probably due to necrosis and liquefaction of infarction. Right lower lobectomy was discussed but not performed because of the patient’s condition. She required frequent intravenous antibiotics but is nowadays, a year after transplantation, in good clinical condition without antibiotic treatment besides the usual PJP prophylaxis (trimethoprim/sulfamethoxazole).
Case 2 A 51-year-old male, with a history of COPD due to severe alpha-1-antitrypsin deficiency, was admitted to our hospital 2 months after his double lung transplantation, with severe left-hand side pleuritic chest pain on deep inspiration and fever lasting for several days. He denied trauma, sputum production, chills, night sweats, or shortness of breath. The patient had no previous history of VTE and no anticoagulation during his readmission. Physical examination demonstrated, besides fever (38.8 C) and left-hand side chest pain, no abnormalities. A chest CT scan revealed PE in the left upper lobe branch of the left pulmonary artery with a subpleural cavitation due to infarction (Figure 4). We started anticoagulation and our 422
Major surgery is a well known and important risk factor for VTE,1 but in lung transplant recipients PE may occur more frequently compared to general surgical population.3 The incidence of PE in lung transplant recipients is 27% (review of autopsy reports).3 The pathophysiology of this discrepancy between PE incidences in lung transplant recipients and general population has not been elucidated yet. An association between thromboembolic events in lung transplant recipients and a hypercoagulable state (for example elevated fibrinogen, factors VIII, IX, and/or XI level, and factors II and V mutation)5 has been reported by Izbicki et al whereas Yegen et al demonstrated that older age, diabetes, and pneumonia increase the rate of VTE in lung transplant recipients.2 The increased risk for older patients may be due to an elevation of coagulation factors. Diabetes hinders fibrinolysis and increases the levels of plasminogen activator inhibitor-1 while pneumonia leads to reduced mobility, which is a well-known risk factor for VTE. 2 Moreover, cytomegalovirus infections have been associated with VTE in renal transplant recipients.6 Furthermore, the immunosuppressant agents have been linked with thrombotic events in solid organ transplant recipients.7 In renal transplant recipients increased levels of plasminogen activator inhibitor, fibrinogen, and von Willebrand factor were reported during cyclosporinebased therapy and therefore shift the balance of the hemostatic system toward a prothrombotic state.7 However, in patients treated with mycophenolate mofetil and tacrolimus, the aggregation response to collagen (the platelet aggregation) was significantly decreased.7 Pulmonary embolism was reported more frequently in lung transplant recipients compared with heart-lung recipients, which suggests that pulmonary arterial anastomotic site can possibly be a thrombogenic surface.3 Burns et al demonstrated that in 37.5% of PE diagnosed in lung transplant recipients, a pulmonary infarction coexisted,4 whereas in general population only approximately 10% of pulmonary emboli cause infarction.8 Pulmonary infarction is uncommon in the general population because of the 3 potential oxygen sources of the pulmonary parenchyma: the pulmonary arteries, the bronchial arteries, and the airways.8 Pulmonary infarction does not develop unless 2 of these 3 sources are compromised as in patients with significant cardiopulmonary disease.8 Therefore, pulmonary infarction is common in lung transplant recipients because bronchial arteries are not anastomosed during lung transplantation procedure. The risk of pulmonary infarction from a PE is greatest in the immediate postoperative period because the newly transplanted lung does not have an alternate blood supply.9 The prevalence of PE was highest, at 36.4%, in the early group (1-30 postoperative days) compared with 20.0% and 23.8% in the
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Figure 2. Chest computed tomography (CT) scan (sagittal view). A, The thick arrow shows filling defects (pulmonary embolism). The thin arrow indicates the presence of a pulmonary infarction and a small pleural effusion. B, Lung window settings of the same image demonstrate an area of wedge-shaped hyperattenuation (infarction), an ancillary finding of a small pleural effusion and ‘‘a vascular sign’’(arrow).
Figure 3. Chest computed tomography (CT) scan shows the right lower lobe cavity (arrow) and an air-fluid level, suggestive of an empyema with an associated bronchopleural fistula.
intermediate (31-365 days) and late (>365 days) groups, respectively.3 The risk of pulmonary infarction after PE is thought to decrease over time due to the development of collateral circulation.4 However, despite the development of collateral bronchial circulation with time, this collateral blood supply may
Figure 4. Chest computed tomography (CT) scan shows the left upper lobe cavity (arrow).
not be sufficient to prevent infarction after PE later in the postoperative course.9 In conclusion, the presentation of a PE in lung transplantation is not classical and symptoms mimicking an infection can be caused by a PE complicated by a pulmonary infarction. Typically, the absence or poorly development of the collateral bronchial circulation may predispose lung transplant recipients 423
424 to develop postembolic pulmonary infarction and eventually cavitation, which may cause significant morbidity. Declaration of Conflicting Interests The author(s) declared no conflicts of interest with respect to the authorship and/or publication of this article.
Funding The author(s) received no financial support for the research and/or authorship of this article.
References 1. Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008; 358(10):1037-1052. 2. Yegen HA, Lederer DJ, Barr RG, et al. Risk factors for venous Thromboembolism after lung transplantation. Chest. 2007; 132(2):547-553. 3. Burns KE, Iacono AT. Pulmonary embolism on postmortem examination: an under-recognised complication in lungtransplant recipiens? Transplantation. 2004;77(5):692-698.
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Clinical and Applied Thrombosis/Hemostasis 17(4) 4. Burns KE, Iacono AT. Incidence of clinically unsuspected pulmonary embolism in mechanically ventilated lung transplant recipients. Transplantation. 2003;76(6):964-968. 5. Izbicki G, Bairey O, Shitrit D, Lahav J, Kramer MR. Increased thromboembolic events after lung transplantation. Chest. 2006; 129(2):412-416. 6. Kazory A, Ducloux D, Coaquette A, Manzoni P, Chalopin JM. Cytomegalovirus-associated venous thromboembolism in renal transplant recipients: A report of 7 cases. Transplantation. 2004;77(4):597-599. 7. Graff J, Klinkhardt U, Harder S, et al. Immunosuppressive therapy regimen and platelet activation in renal transplant patients. Clin Pharmacol Ther. 2002;72(4):411-418. 8. Parambil JG, Savci CD, Tazelaar HD, Ryu JH. Causes and presenting features of pulmonary infarctions in 43 cases identified by surgical lung biopsy. Chest. 2005;127(4): 1178-1183. 9. Kroshus TJ, Kshettry VR, Hertz MI, Bolman RM 3rd. Deep venous thrombosis and pulmonary embolism after lung transplantation. J Thorac Cardiovasc Surg. 1995;110(2):540-544.
