Does Antiplatelet Therapy Increase the Risk of Hemoptysis During Percutaneous Transthoracic Needle Biopsy of a Pulmonary Lesion?

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1 Cardiopulmonary Imaging Original Research Song et al. Antiplatelet Therapy and Risk of Bleeding During Pulmonary Biopsy Cardiopulmonary Imaging Original Research Yong Sub Song 1 Chang Min Park 1 Kyung Woo Park 2 Kwang Gi Kim 3 Hyun-Ju Lee 1 Mi-Suk Shim 1 Jin Mo Goo 1 Song YS, Park CM, Park KW, et al. Keywords: aspirin, antiplatelet, bleeding, biopsy, hemoptysis, PTNB DOI: /AJR Received March 19, 2012; accepted after revision June 10, This study was supported by a research grant from the Korean Foundation for Cancer Research (grant number CB ) and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (grant number ). 1 Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, 101 Daehangno, Jongno-gu, Seoul , Korea. Address correspondence to C. M. Park (cmpark@radiol.snu.ac.kr). 2 Department of Internal Medicine, Cardiovascular Center, Seoul National University College of Medicine, Seoul, Korea. 3 Department of Biomedical Engineering, Division of Basic and Applied Sciences, National Cancer Center, Gyeonggi-Do, Korea. AJR 2013; 200: X/13/ American Roentgen Ray Society Does Antiplatelet Therapy Increase the Risk of Hemoptysis During Percutaneous Transthoracic Needle Biopsy of a Pulmonary Lesion? OBJECTIVE. The purpose of this article is to evaluate whether antiplatelet therapy increases the occurrence and severity of percutaneous transthoracic needle biopsy (PTNB) related hemoptysis. MATERIALS AND METHODS. Our institutional review board approved this retrospective study, with waiver of informed consent. From May 2007 to December 2009, 1251 patients undergoing 1346 PTNBs constituted our study population. Of these PTNBs, 163 were performed in patients who had suspended antiplatelet therapy for less than 10 days (mean discontinuation time, 2.56 ± 2.35 days), and these patients were classified as antiplatelet agent users: 143 patients with single aspirin (mean discontinuation time, 2.55 ± 2.35 days), 12 patients with single clopidogrel (mean discontinuation time, 2.33 ± 2.10 days), and eight patients with dual-antiplatelet therapy (i.e., aspirin plus clopidogrel; mean discontinuation time, 3.12 ± 2.90 days). The influence of antiplatelet therapy on the occurrence and severity of PTNBrelated hemoptysis was retrospectively evaluated. RESULTS. Among 1346 PTNBs, there were 128 cases (9.5%) of hemoptysis, including 21 cases of severe hemoptysis (1.6%). Multivariate analysis revealed that dual-antiplatelet therapy (odds ratio [OR], 10.09), female sex (OR, 1.88), smaller lesions (OR, 0.88), deeply located lesions (OR, 1.17), and the use of cutting needles (OR, 3.22) were independent risk factors for overall hemoptysis. For severe hemoptysis, dual-antiplatelet therapy (OR, 13.02), ground-glass nodules (OR, 8.86), and deeply located lesions (OR, 1.24) were proven to be independent risk factors. Single-antiplatelet therapy suspended for less than 10 days was not a significant risk factor for either overall or severe hemoptysis. CONCLUSION. Single-antiplatelet therapy suspended for less than 10 days is not an independent risk factor for the occurrence of PTNB-related hemoptysis, whereas dual-antiplatelet therapy increases its risk. P ercutaneous transthoracic needle biopsy (PTNB) is a highly accurate and minimally invasive diagnostic procedure for indeterminate pulmonary lesions [1 5]. PTNB has generally been known to be a safe procedure; however, several PTNB-related complications are known to occur, with severity ranging from self-limiting to fatal in some cases [1 8]. Among them, hemoptysis is the second most common complication of PTNB after pneumothorax [1 11]. Although PTNBrelated hemoptysis is usually self-limiting, at times it can be severe enough to require immediate therapeutic intervention or medical treatment [3 6]. At present, hemoptysis remains one of the major causes of PTNBrelated mortality, along with air embolism [2, 5, 7, 9]. Antiplatelet agents, which inhibit platelet function [12 14], have been used to decrease the risks of myocardial infarction, thrombosis within coronary artery stents, ischemic stroke, and cardiovascular death in patients at increased cardiovascular risk [15]. In clinical practice, patients receive either single- or dual-antiplatelet therapy, typically consisting of aspirin, clopidogrel, or both, for either a prolonged period or lifelong in certain situations [16]. It is also well known, however, that antiplatelet agents can increase the risk of various bleeding complications, such as spontaneous gastrointestinal bleeding and spontaneous intracranial hemorrhage, and can increase the risk of excessive bleeding during surgery [12]. Therefore, in patients who undergo PTNB, discontinuation of antiplatelet therapy may be an option to limit any additional possibility of hemoptysis AJR:200, May 2013

2 Antiplatelet Therapy and Risk of Bleeding During Pulmonary Biopsy Yet, because discontinuation of antiplatelet therapy potentially increases the risk of a cardiac event or stroke [17, 18], the harm and benefit of discontinuing or continuing antiplatelet therapy in patients undergoing PTNB must be examined more closely. Currently, however, whether antiplatelet therapy increases the occurrence of hemoptysis or causes severe hemoptysis during PTNB in clinical practice remains unclear. The British Thoracic Society s guidelines for PTNB [4] state that there is, as of yet, no evidence on this issue; thus, no guidelines on whether antiplatelet agents should be discontinued before PTNB have been given. In a previous study dealing with this topic, it was reported that single-aspirin therapy before PTNB did not increase the risk of bleeding complications associated with PTNB [19]. That study, however, possessed a critical limitation in the lack of consideration given to other well-known risk factors for bleeding, including lesion size and lesion depth, which could have acted as significant confounding variables [10]. We think that the question of whether antiplatelet therapy practically increases the occurrence of overall or severe hemoptysis in patients undergoing PTNB still remains to be answered. Furthermore, to our knowledge, there have been no studies that have evaluated the risk of dualantiplatelet therapy on PTNB-related hemoptysis. The purpose of our study, therefore, was to evaluate whether antiplatelet therapy, more specifically single- and dual-antiplatelet therapy, increases the occurrence and severity of PTNB-related hemoptysis. Materials and Methods Our institutional review board approved this retrospective study. The requirement for informed consent was waived. Study Population Between May 2007 and December 2009, 1501 consecutive PTNB procedures were performed in 1338 patients in a tertiary-referral hospital. The procedures were performed by consultant radiologists or by trainee radiologists under a consultant s supervision. Among these procedures, cases that met the following criteria comprised the study population: performance of procedures for an intrapulmonary lesion, availability of chest CT images within 7 days before the procedure, availability of electronic medical records of the patients medication history before the procedure, availability of coagulation test results within 28 days before PTNB, and no history of using anticoagulants before PTNB. We excluded patients with abnormal coagulation profiles, such as a prothrombin time greater than 1.5 international normalized ratio, activated partial thromboplastin time longer than 50 seconds, or a serum platelet count of less than /μl. Finally, 1346 PTNB procedures in 1251 patients (757 men and 494 women; mean age, ± years) constituted our study population. Among them, 93 patients underwent PTNB twice, one patient did three times, and the remaining 1157 patients underwent PTNB once. Each PTNB procedure was counted as a new procedure. PTNB procedures were performed under the guidance of fluoroscopy in 898 procedures, CT in 406 procedures, and sonography in 42 procedures. An TABLE 1: Results of Univariate Analysis to Determine Influencing Factors for Hemoptysis During Percutaneous Transthoracic Needle Biopsy (PTNB) Variables Hemoptysis Group (n = 128) Nonhemoptysis Group (n = 1218) No antiplatelet therapy 105 (82.0) 1078 (88.5) Single-aspirin therapy (2.55) b 16 (12.5) 127 (10.4) Single-clopidogrel therapy (2.33) b 3 (2.3) 9 (0.7) Dual-antiplatelet therapy (3.12) b 4 (3.1) 4 (0.3) p a Age (y) c ± ± d Sex < e Male 58 (45.3) 753 (61.8) Female 70 (54.7) 465 (38.2) Lesion size (mm) c ± ± < d Lesion depth (mm) c ± ± d Lesion internal characteristics f Solid 118 (92.2) 1177 (96.6) Ground-glass nodule 10 (7.8) 41 (3.4) Lesion location Upper and middle lobes 78 (60.9) 709 (58.2) Lower lobe 50 (39.1) 509 (41.8) Imaging guidance modality Fluoroscopy 86 (67.2) 812 (66.7) CT 40 (31.2) 366 (30.0) Sonography 2 (1.6) 40 (3.3) Cutting biopsy needle Yes 121 (94.5) 1026 (84.2) No 7 (5.5) 192 (15.8) Coaxial biopsy technique Yes 40 (31.3) 435 (35.7) No 88 (68.8) 783 (64.3) e f e e Prothrombin time (international normalized ratio) c 1.01 ± ± d Activated partial thromboplastin time (s) c ± ± d Platelet count ( 10 3 /μl) c 249 ± ± d Note Except where indicated, data are no. (%) of patients undergoing PTNB. a Calculated with the linear-by-linear association test. b Number in parentheses is average days of discontinuation before the PTNB. c Data are mean ± SD. d Calculated with the independent sample Student t test. e Calculated with the Pearson chi-square test. f Calculated with the Fisher exact test. AJR:200, May

3 Song et al. 18-gauge cutting needle (Stericut, TSK Laboratory) was used for core biopsy, and a 22-gauge needle (Westcott, Medical Device Technologies) was used for aspiration biopsy. Of the 1346 procedures, the coaxial biopsy technique was used in 475 procedures, and the single-needle technique was adopted in the remaining 871 procedures. Study Variables Clinical data for the occurrence and severity of hemoptysis during or immediately after PTNB were recorded by one author on the basis of the PTNB procedure database and electronic medical records of our hospital. Patients with PTNB-related hemoptysis were categorized into two groups: those with mild hemoptysis and those with severe hemoptysis. Severe hemoptysis was defined as hemoptysis estimated to be greater than 100 ml during or immediately after PTNB or causing hemodynamic instability, requiring blood transfusion, or invasive interventional procedures [10, 11, 20]. Mild hemoptysis was defined as hemoptysis that did not fulfill the definition of severe hemoptysis. Detailed information regarding patients antiplatelet therapy, such as the kind and dosage of antiplatelet agents used, as well as the duration of therapy discontinuation before PTNB, if any, were investigated. Antiplatelet users were categorized into three groups: those who had received singleaspirin therapy, those who had received singleclopidogrel therapy, and those who had received dual-antiplatelet therapy consisting of both aspirin and clopidogrel. In the current study, we categorized former antiplatelet users as non antiplatelet users if their discontinuation duration was 10 days or longer. Previous reports have shown the platelet turnover period to be 7 10 days, with no remaining antiplatelet effect after 10 days [12 14]. Among the total of 1346 PTNB procedures, 179 patients had a history of either single-aspirin, single-clopidogrel, or dual-antiplatelet therapy. Among these 179 patients, 16 had discontinued antiplatelet therapy for 10 days or longer before PTNB, thus classifying them as non antiplatelet users. The remaining 163 PTNBs were performed in patients who had suspended antiplatelet therapy for less than 10 days (mean discontinuation time, 2.56 ± 2.35 days) and were classified as antiplatelet users, because the antiplatelet effect of these agents is considered to remain in the blood. There were 143 patients (10.6%) receiving singleaspirin therapy (mean discontinuation time, 2.55 ± 2.35 days; range, 0 9 days), 12 patients (0.9%) receiving single-clopidogrel therapy (mean discontinuation time, 2.33 ± 2.10 days; range, 0 6 days), and eight patients (0.6%) receiving dual-antiplatelet therapy (mean discontinuation time, 3.12 ± 2.90 days; range, 0 8 days), which consisted of both aspirin and clopidogrel. The discontinuation times for each group were not statistically different according to the Kruskal-Wallis test (p = 0.891). The dosage of antiplatelet agents was mg/day for aspirin and 75 mg/day for clopidogrel. Patients demographic features, as well as other potential risk factors for hemoptysis (e.g., coagulation profiles; size, depth, location, and internal characteristics of the target lesion; and biopsy technique used), were also recorded by one author. Target size was defined as its longest diameter, and lesion depth was defined as the distance between the point of pleural puncture to the nearest edge of the target along the needle path using preprocedural or intraprocedural CT images [5]. Lesion location was determined in terms of pulmonary lobe. With respect to the targets internal characteristics, we classified target lesions as either solid or ground-glass nodules. Ground-glass nodules included pure ground-glass nodules and partly solid nodules. Solid lesions included solid nodules or masses, consolidations, and cavitary lesions. As for the PTNB techniques used, the imaging modality used for guidance, the needle type (cutting biopsy needle vs aspiration needle), and pleural puncture technique used (coaxial needle technique vs single needle technique) were recorded. Statistical Analysis All statistical analyses were performed using SPSS (version 18.0 for Windows, SPSS) and STATA software (version 10, StataCorp). The relationship between the occurrence and severity of hemoptysis during or after PTNB, as well as usage of antiplatelet therapy and other potential risk factors, were analyzed using the Student t test, Pearson chi-square test, Fisher exact test, or linear-by-linear association test, as appropriate. A p value of less than 0.05 was considered to indicate a significant difference. Subsequently, logistic regression analysis with generalized estimation equations was performed to determine the independent risk factors for the occurrence of overall hemoptysis. Variables with a p value of less than 0.10 in univariate analysis were used as input variables for multiple logistic regression analysis. In determining the independent risk factors for severe hemoptysis, however, we were not able to perform classic multivariate logistic regression analysis because of the complete separation phenomenon. To solve this statistical problem, we performed penalized maximum likelihood estimation to determine the independent risk factors for severe hemoptysis [21]. Results Of 1346 procedures, PTNB-related hemoptysis occurred in 128 cases (9.5%), including 107 cases of mild hemoptysis and 21 cases of severe hemoptysis. Of the 21 severe hemoptysis cases, one patient needed intubation because of severe desaturation caused by aspiration of hemoptysis blood, and one patient underwent bronchial artery embolization for massive hemoptysis. There were no fatalities or significant physical disabilities caused by PTNB-related hemoptysis in our study. Table 1 summarizes the demographic, clinical, and technical features of the hemoptysis and nonhemoptysis groups. There were significant differences between the two groups in terms of antiplatelet therapy used; patient sex; lesion size, depth, and internal characteristics; and biopsy needle type used. Multiple logistic regression analysis with generalized estimation equation revealed that dual-antiplatelet therapy (adjusted odds ratio [OR], 10.09), female sex (OR, 1.88), smaller lesions (OR, TABLE 2: Results of Multivariate Logistic Regression Analysis to Determine Risk Factors for Hemoptysis During Percutaneous Transthoracic Needle Biopsy (PTNB) Variables Odds Ratio (95% CI) p No antiplatelet therapy Reference Single-aspirin therapy (2.55) a 1.38 ( ) Single-clopidogrel therapy (2.33) a 2.26 ( ) Dual-antiplatelet therapy (3.12) a ( ) Female sex 1.88 ( ) Lesion size 0.88 ( ) Deeply located lesion 1.17 ( ) < Ground-glass nodule 1.94 ( ) Cutting biopsy needle 3.22 ( ) a Number in parentheses is average days of discontinuation before the PTNB AJR:200, May 2013

4 Antiplatelet Therapy and Risk of Bleeding During Pulmonary Biopsy 0.88), deeply located lesions (OR, 1.17), and use of a cutting biopsy needle (OR, 3.22) were significant independent risk factors of overall hemoptysis (Table 2). Interestingly, singleantiplatelet therapy suspended for less than 10 days (either single-aspirin or single-clopidogrel therapy) was not a significant risk factor for overall hemoptysis (Table 2). Table 3 summarizes the demographic, clinical, and technical features of the severe hemoptysis group. There were significant differences between the severe hemoptysis group and the nonsevere hemoptysis group (mild and nonhemoptysis groups) with regard to the antiplatelet therapy used, patient age, and lesion depth and internal characteristics. These variables and the use of a cutting biopsy needle (p = 0.060) were used as input variables for penalized maximum likelihood estimation (Table 4). At penalized maximum likelihood estimation, dual-antiplatelet therapy (OR, 13.02), ground-glass nodule as lesions internal characteristics (OR, 8.86), and deeply located lesions (OR, 1.24) were significant independent risk factors of severe hemoptysis. Single-antiplatelet therapy (either single-aspirin or single-clopidogrel therapy) suspended for less than 10 days was not a significant risk factor for severe hemoptysis. Among the 21 patients with severe hemoptysis, six patients (28.6%) had either ground-glass nodule or dual-antiplatelet therapy; however, no patients with severe hemoptysis had both ground-glass nodule and dual-antiplatelet therapy simultaneously (Table 3). Discussion In the current study, we found that single-aspirin or -clopidogrel antiplatelet therapy suspended for less than 10 days before PTNB is not a significant risk factor for both overall hemoptysis and severe hemoptysis in patients with normal coagulation profiles, whereas dual-antiplatelet therapy suspended for less than 10 days before PTNB was shown to be a significant risk factor. As for single-aspirin therapy, our observations are in line with previous studies such as that by Herth et al. [22], who prospectively investigated and reported that aspirin did not significantly increase the occurrence and severity of bleeding complications in patients undergoing bronchoscopic transbronchial lung biopsy. The authors concluded that patients did not have to be encouraged to discontinue aspirin medication before their scheduled bronchoscopic transbronchial biopsy [22]. With respect to PTNB, Atwell et TABLE 3: Results of Univariate Analysis to Determine Influencing Factors for Severe Hemoptysis During Percutaneous Transthoracic Needle Biopsy (PTNB) Variables Severe Hemoptysis (n = 21) Nonsevere Hemoptysis a (n = 1325) p b No antiplatelet therapy 15 (71.4) 1168 (88.2) Single-aspirin therapy (2.55) c 4 (19.0) 139 (10.5) Single-clopidogrel therapy (2.33) c 1 (4.8) 11 (0.8) Dual-antiplatelet therapy (3.12) c 1 (4.8) 7 (0.5) Age (y) d ± ± e Sex f Male 11 (52.4) 800 (60.4) Female 10 (47.6) 525 (39.6) Lesion size (mm) d ± ± e Lesion depth (mm) d ± ± e Lesion internal characteristics g Solid 16 (76.2) 1279 (96.5) Ground-glass nodule 5 (23.8) 46 (3.5) Lesion location Upper and middle lobes 13 (61.9) 774 (58.4) Lower lobe 8 (38.1) 551 (41.6) Imaging guidance modality Fluoroscopy 12 (57.1) 886 (66.9) CT 9 (42.9) 397 (29.9) Sonography 0 (0.0) 42 (3.2) Cutting biopsy needle Yes 21 (100.0) 1126 (85.0) No 0 (0.0) 199 (15.0) Coaxial biopsy technique Yes 10 (47.6) 465 (35.1) No 11 (52.4) 860 (64.9) g g f f Prothrombin time (international 1.01 ± ± e normalized ratio) d Activated partial thromboplastin time (s) d ± ± e Platelet count ( 10 3 /μl) d 238 ± ± e Note Except where indicated, data are no. (%) of patients undergoing PTNB. a Nonsevere hemoptysis group consists of mild and nonhemoptysis groups. b Calculated with the linear-by-linear association test. c Number in parentheses is average days of discontinuation before the PTNB. d Data are mean ± SD. e Calculated with the independent sample Student t test. f Calculated with the Pearson chi-square test. g Calculated with the Fisher exact test. al. [19] analyzed 1174 PTNB procedures and also reported that aspirin did not increase the risk of severe bleeding. However, they did not include potential known risk factors of PTNBrelated bleeding, such as lesion size and depth, in their analysis; thus, their findings may have been subject to possible bias due to confounding factors. On the basis of our observations AJR:200, May

5 Song et al. as well as those of a previous study [22], we think that single-aspirin therapy suspended for less than 10 days before PTNB indeed does not increase the occurrence or severity of hemoptysis in patients with normal coagulation profiles. As for clopidogrel, however, there are some discrepancies. Ernst et al. [23] reported that single-clopidogrel therapy greatly increased bleeding complications in patients undergoing bronchoscopic transbronchial biopsy. In fact, in their prospective study [23], they observed an 89% bleeding rate in 18 patients receiving clopidogrel only. This difference in the risk of bleeding complications between aspirin and clopidogrel may come from the different pharmacodynamics of each agent. Aspirin is an irreversible cyclooxygenase-1 inhibitor that blocks thromboxane A 2 production, thereby reducing platelet activation stimulated by thromboxane A 2 [24]. However, aspirin minimally inhibits other platelet activation pathways, thus allowing platelet activation by other agonists such as adenosine diphosphate [25]. In contrast, clopidogrel is a P2Y 12 adenosine diphosphate receptor antagonist that inhibits P2Y 12 -mediated platelet activation pathways induced by adenosine diphosphate [26]. P2Y 12 amplifies not only platelet aggregation but also the other functional consequences of activation, including granule release and platelet procoagulant activity [27]. Consequently, clopidogrel inhibits all of these important processes, which can contribute to arterial thrombosis [27]. In the present study, we also observed that both overall and severe hemoptysis were more frequent in single-clopidogrel users than in the non antiplatelet users and singleaspirin users, although their differences did not reach a statistical significance. The lack of statistical significance, however, may be because the cohort of patients using clopidogrel was limited to 12 patients in our study. Further studies with a larger study population are warranted to better assess the actual impact of single-clopidogrel usage on PTNBrelated hemoptysis. Dual-antiplatelet therapy with aspirin plus clopidogrel was found to be an independent risk factor for both overall hemoptysis and severe hemoptysis, and its ORs for both overall and severe hemoptysis were greater than 10 compared with those for non antiplatelet users. The risk increase from dual-antiplatelet therapy was significant not only compared with non antiplatelet users but even when compared against patients undergoing single-antiplatelet therapy. Ernst et al. [23] also reported a 100% bleeding rate in 12 patients receiving both clopidogrel and aspirin and suggested that combined aspirin use exacerbated the effect of clopidogrel on bleeding. Thus, our result is well consistent with these previous observations. A previous meta-analysis [28] reported that patients treated with dual-antiplatelet therapy had an approximately 40 50% greater risk of major and minor bleeding compared with those receiving single-antiplatelet therapy. In addition, other investigators [29, 30] have also reported that the risk of bleeding increased when clopidogrel was added to other antiplatelet drugs in patients undergoing coronary bypass graft surgery. These previous results also support our observations. In this context, the Canadian Cardiovascular Society Guidelines [16] recommend that patients who receive dual-antiplatelet therapy using aspirin plus clopidogrel should discontinue taking clopidogrel 7 10 days even before a minor procedure with low risk for bleeding, such as minor dental, eye, or skin surgery. On the basis of our study results and other related studies [16, 23, 28 30], we suggest that patients who receive dual-antiplatelet therapy and are planning to undergo PTNB should be advised to discontinue clopidogrel before PTNB, because bleeding including hemoptysis is a main complication of PTNB. One of the interesting results of our study is that ground-glass nodule as a lesion s internal characteristics is an independent risk factor for severe hemoptysis. Several explanations can be possible. First, preserved bronchovascular structures within a groundglass nodule can increase the probability of iatrogenic communication between damaged bronchi and pulmonary vessels during biopsy and can influence the occurrence of severe hemoptysis. Second, the lack of compactness of ground-glass nodules can hinder compression of the biopsy site due to the lesion itself, thus aggravating the degree of bleeding and prolonging the bleeding time and negatively affecting severe hemoptysis. The fact that ground-glass nodules did not gain statistical significance in terms of overall hemoptysis may be related to the relatively small number of ground-glass nodules in our study. Other risk factors we found include deeply located lesions, smaller lesions, and the usage of a cutting biopsy needle. Of these risk factors, deeply located lesions and smaller lesions have been reported as risk factors for bleeding in several other studies [10, 11]. The smaller or more deeply located the lesions are, the more difficult they are to sample successfully, resulting in longer procedural time and increased number of needle repositionings required. Thus, lung parenchymal injury due to biopsy can be greater and there may be a greater risk for hemoptysis. Likewise, the use of a cutting biopsy needle is a significant risk factor because the biopsy needle used is greater in diameter, thus increasing the risk of lung parenchymal injury during biopsy [2]. Our study has several limitations. First, our study had a retrospective design, with only eight patients receiving dual-antiplatelet therapy and 12 single-clopidogrel users, which hindered a more confirmative statement on this issue. Second, our study included and classified patients who had suspended antiplatelet therapy for less than 10 days as antiplatelet users (single- or dual-antiplatelet therapy). Thus, we cannot confirmatively conclude whether the continuation of single-antiplatelet therapy TABLE 4: Results of Penalized Maximum Likelihood Estimation to Determine Risk Factors for Severe Hemoptysis During Percutaneous Transthoracic Needle Biopsy (PTNB) Variables Odds Ratio (95% CI) p No antiplatelet therapy Reference Single-aspirin therapy (2.55) a 1.84 ( ) Single-clopidogrel therapy (2.33) a 3.84 ( ) Dual-antiplatelet therapy (3.12) a ( ) Older age 1.04 ( ) Ground-glass nodule 8.86 ( ) < Deeply located lesion 1.24 ( ) Cutting biopsy needle 6.55 ( ) a Number in parentheses is average days of discontinuation before the PTNB AJR:200, May 2013

6 Antiplatelet Therapy and Risk of Bleeding During Pulmonary Biopsy before PTNB would be safe. As for dual-antiplatelet therapy, we can suggest that dual-antiplatelet therapy being continued or suspended for less than 10 days before PTNB is not safe. Third, we excluded patients who had abnormal coagulation profiles; thus, our results cannot be applied to patients who had abnormal coagulation profiles. However, regardless of the antiplatelet therapy used, abnormal coagulation profiles are already considered as a relative contraindication [4]. In our study, we focused on the hemoptysis risk of antiplatelet therapy in patients with normal coagulation profiles. Fourth, we considered only hemoptysis as a bleeding complication after PTNB for the purposes of our study. Lung parenchymal hemorrhage and hemothorax are also wellknown bleeding complications of PTNB that need to be examined [3, 8]. 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