Authors: Bilal Rabahoğlu, Nuri Tutar, Nur Aleyna Yetkin, Burcu Baran, İnci Gülmez
Categories: Case Report, Aspirin, Bleeding, Bronchoscopy, Clopidogrel, Endobronchial biopsy
Source: BMC Pulmonary Medicine
Authors: Bilal Rabahoğlu, Nuri Tutar, Nur Aleyna Yetkin, Burcu Baran, İnci Gülmez
Some patients undergoing pulmonary procedures are on at least one antiplatelet or anticoagulant agent. Discontinuing these treatments can be challenging due to the risk of severe complications, particularly following acute coronary event. While studies indicate that clopidogrel cessation is necessary before transbronchial biopsy, others suggest it may be safely continued for procedures such as endobronchial ultrasound-guided transbronchial needle aspiration. There is limited literature on performing endobronchial biopsies while patients are on clopidogrel (a P2Y12 inhibitor), with only one case report available.
In our three cases, the patients had endobronchial lesions causing partial or complete airway obstruction, leading to severe dyspnea and wheezing. Two of the patients were on dual antiplatelet therapy (DAPT) due to recent coronary artery syndrome treated with coronary stents, while the third was receiving the same treatment for peripheral artery disease managed with a stent. Endobronchial biopsies (EBB) were performed on all three patients without any major complications.
Although it is typically recommended to discontinue clopidogrel 5–7 days prior to the procedure, early diagnosis and treatment are crucial in certain cases. In these situations, where the benefits may outweigh the risks, EBB can be performed with appropriate precautions. Through our case reports, we aim to encourage further prospective studies and the establishment of updated guidelines, particularly concerning EBB in patients receiving DAPT.
In a single-center study, approximately 25% of patients undergoing pulmonary procedures are on at least one antiplatelet or anticoagulant agent [1]. In another study by Takashima et al., among patients undergoing transbronchial lung biopsy (TBLB) via flexible bronchoscopy (FB), 18.5% were receiving antiplatelet therapy and 6.1% were on anticoagulant therapy [2]. For some patients using these agents for the primary prevention of cardiovascular disease, temporary cessation may be possible. However, for patients on dual antiplatelet therapy (DAPT), which typically includes clopidogrel (a P2Y12 inhibitor) and aspirin (a cyclooxygenase [COX] enzyme inhibitor), following acute coronary artery disease (CAD), temporary cessation may not be an option due to the risk of severe complications [3].
The bleeding risk varies depending on the bronchoscopic procedure, with TBLB carrying the highest risk, followed by therapeutic bronchoscopy, endobronchial biopsy (EBB), transbronchial needle aspiration (TBNA), bronchoalveolar lavage (BAL), and exploratory bronchoscopy, in a decreasing order of bleeding risk. To prevent bleeding, it is generally recommended to discontinue clopidogrel 5–7 days before invasive bronchoscopic procedures. In contrast, the continuation of aspirin has not been associated with increased bleeding risk [4]. Compared to aspirin, clopidogrel is less extensively studied but remains a critical drug for preventing in-stent thrombosis, which can lead to myocardial infarction. However, its use during TBLB is discouraged due to the high bleeding risk. Interestingly, a 12-case report noted no increased bleeding following endobronchial ultrasound-guided TBNA (EBUS-TBNA) in patients on clopidogrel [3].
In our three consecutive cases, the patients presented with endobronchial lesions causing partial or complete airway obstruction, resulting in severe dyspnea and wheezing. All three patients presented with severe respiratory symptoms, necessitating urgent diagnostic evaluation and prompt initiation of treatment. Two of these patients were on DAPT due to recent coronary artery syndrome treated with coronary stents, while the third was on the same therapy for peripheral artery disease managed with a stent. The case series was approved by the Institutional Review Board at our faculty (approval 2025/226).
The aim of this case series is to highlight the possibility of performing EBB in patients on clopidogrel to encourage further prospective studies. Since comprehensive data on this subject are lacking, this report aims to guide clinical decisions when the benefits of the procedure outweigh the risks.
A 77-year-old male patient presented to our clinic following a one-week hospitalization at another facility. The patient reported persistent symptoms of cough, dyspnea, and wheezing. He had a 40-year history of smoking and a diagnosis of CAD. One month prior, he had undergone coronary angiography with stent placement and was subsequently started on pantoprazole, aspirin and clopidogrel by his cardiologist.
Chest computed tomography (CT) revealed bilateral emphysema and an endobronchial lesion in the distal portion of the trachea (Fig. 1a). Due to the patient’s progressive dyspnea and wheezing, we planned a FB with EBB to confirm the diagnosis and initiate treatment promptly. Given the patient’s use of DAPT, we consulted the Cardiology department regarding the possibility of temporarily discontinuing the treatment for the biopsy. The cardiologists recommended continuing DAPT for at least three months post-stenting but allowed for the temporary cessation of aspirin if the procedure was urgent. FB was performed while the patients was on DAPT treatment.
Fig. 1a an endobronchial lesion seen in the distal part of the trachea (blue arrow), b endobronchial lesion seen obstructing distal part of trachea during bronchoscopy, c a part of the lesion removed using retrieval basket
During the FB, an endobronchial lesion was identified in the distal trachea near the carina (Fig. 1b). Seven biopsies were obtained using a 1.8 mm forceps. Given the minimal procedure-related bleeding and the patient’s severe respiratory symptoms, partial debulking of the lesion was subsequently done using an electrocautery catheter and a retrieval basket to alleviate symptoms (Fig. 1c). On a bleeding grading scale from 1 to 4, mild procedural bleeding requiring only suctioning (grade 1) was observed, with no major bleeding complications reported [5]. The patient was subsequently diagnosed with squamous cell carcinoma and commenced treatment immediately.
A 74-year-old male patient, an ex-smoker with a 50-year smoking history, presented to the emergency department with symptoms of cough, sputum production, wheezing, and severe dyspnea. His medical history included diabetes mellitus (DM), hypertension, CAD, and lung adenocarcinoma. One year earlier, he had been diagnosed with lung adenocarcinoma, which was treated with a left upper lobe resection followed by chemoradiotherapy. One month prior to admission, the patient experienced a myocardial infarction and was initiated on pantoprazole, aspirin and clopidogrel.
Chest CT revealed the absence of the left upper lobe (post-lobectomy), a central cavitation in the left lung, and an endobronchial lesion in the left main bronchus (Fig. 2a and b). The cavitation was suspected to be a second primary lung cancer, warranting a biopsy. Given the recent myocardial infarction, clopidogrel cessation was not advised, so FB was performed while the patient remained on DAPT. During FB, an endobronchial lesion was observed in the left main bronchus (Fig. 2c). Six biopsies were obtained with a 1.8 mm forceps, grade 1 bleeding was reported. The patient was diagnosed with recurrent lung adenocarcinoma and referred to medical oncology for further treatment.
Fig. 2a Cavitation on the left lung, b an endobronchial lesion in the left main bronchus (blue arrow), c lesion image seen during bronchoscopy
A 70-year-old male patient with a history of DM, CAD (with two stents placed in 2010), and prostate adenocarcinoma (surgically treated and followed by radiotherapy) presented with hemoptysis, chest pain, severe dyspnea, and wheezing. The patient also had a 30-year smoking history. Four months prior, he had undergone stent placement for peripheral artery disease in his left leg.
Chest CT revealed narrowing at the entrances to the right middle and lower lobes and the presence of an endobronchial lesion (Fig. 3a). FB was performed, revealing an endobronchial lesion obstructing the right middle and lower lobes, preventing distal advancement of the bronchoscope (Fig. 3b). A total of eight EBB were obtained with a 1.8 mm forceps, with grade 1 bleeding related to the procedure observed. The patient was diagnosed with squamous cell lung carcinoma and was referred for further treatment.
Fig. 3a An endobronchial lesion obstructing the entrance of both right middle and lower lung lobes (blue arrow), b endobronchial lesion observed during bronchoscopy
Generally, bronchoscopy is considered a relatively safe procedure. However, with the emergence of new diagnostic techniques and the widespread use of antiplatelet/anticoagulant therapies, pulmonologists must be familiar with the associated bleeding risks and understand how to minimize these risks without causing thrombotic events [6].
Recent studies suggest that clopidogrel should be withheld 5–7 days before bronchoscopic procedures, while aspirin may be continued to reduce the risk of bleeding. Nevertheless, discontinuing such treatments, particularly following stent placement, can be challenging [4]. Research on antiplatelet therapy and invasive procedures has highlighted the importance of stopping these drugs, especially during TBLB. In a study by Ernst et al., two groups of patients undergoing TBLB were one group receiving clopidogrel alone and the other receiving both aspirin and clopidogrel. The bleeding rate was 16/18 (89%) in the clopidogrel-only group and 12/12 (100%) in the dual therapy group, compared to 20/547 (3.4%) in the control group. Due to the excessive bleeding rates, the study was terminated early. The researchers concluded that aspirin amplifies the bleeding effects of clopidogrel [7].
The risk of bleeding is known to be lower during EBB and TBNA compared to TBLB and therapeutic bronchoscopy [4]. A study by Gil et al. concluded that it is safe to perform EBUS-TBNA in patients receiving antithrombotic agents without discontinuing the therapy [8]. Furthermore, a 12-case report observed no increase in bleeding in patients receiving clopidogrel during EBUS-TBNA [3].
In a consensus on the management of antithrombotic agents during endoscopy, procedures were categorized into three groups based on bleeding low, high, and ultra-high. Examples included diagnostic endoscopy with mucosal biopsy (low risk), polypectomy (high risk), and endoscopic submucosal dissection (ultra-high risk). For low-risk procedures, they recommended continuing DAPT. For high-risk procedures, they advised discontinuing P2Y12 receptor inhibitors 5–7 days prior while continuing aspirin. In ultra-high bleeding risk scenarios, discontinuation of P2Y12 receptor inhibitors 5–7 days before the procedure was recommended. The decision to withhold aspirin depended on the bleeding risk of the procedure and the patient’s thrombotic risk [9].
Generally, EBB is considered a low-risk procedure, with an estimated procedural bleeding risk of approximately 0.43% [10]. However, there is a lack of extensive studies on EBB in patients undergoing antiplatelet treatment. One case report documented a successful EBB in a patient receiving aspirin and prasugrel, with no complications. The patient had recently undergone drug-eluting stent placement and required evaluation for lung cancer recurrence, which led to the procedure being performed while the patient was on these medications [11].
Although EBB carries a lower bleeding risk compared to TBLB, pulmonologists may be hesitant to perform the procedure in patients on DAPT. In our three cases, we ensured that various hemostatic tools (e.g., cold saline, adrenaline, tranexamic acid, Ankaferd blood stopper, balloon catheters) were available before proceeding. FB was performed under local anesthesia (2% Lidocaine) and conscious sedation with fentanyl (25–50 mcg) and midazolam (1–5 mg). Additionally, in the event of bleeding or other complications, we ensured the availability of equipment necessary for intubation and endobronchial blockade, as well as access to intensive care unit admission and/or embolization in collaboration with interventional radiology.
To minimize bleeding risk, cold physiological saline (4 °C) was administered, followed by 1000 adrenaline (diluted 10 with normal saline). The bleeding risks and potential consequences were thoroughly discussed with the patients, and written informed consent was obtained. In all three cases, endobronchial cold saline and adrenaline were applied prophylactically, which may have helped prevent major bleeding during the procedure. Although endobronchial administration of adrenaline may lead to cardiac arrhythmias and is therefore not generally preferred as a first-line treatment, a low prophylactic dose was administered in our cases due to the increased risk of bleeding associated with clopidogrel therapy during biopsy. Despite the absence of controlled clinical trials evaluating the safety and efficacy of endobronchial adrenaline, Khoo et al. emphasized in a correspondence that when adrenaline is required, continuous electrocardiographic monitoring is essential [12]. Furthermore, Steinfort et al. reported that administering adrenaline to the distal airways or alveolar spaces may pose a greater risk of systemic adverse effects compared to administration in more proximal bronchial segments [13]. In our cases, adrenaline was applied locally to the lesion site and not to the peripheral lung regions. Continuous cardiac and blood pressure monitoring was ensured throughout the procedure to promptly detect and manage any potential side effects. It is crucial to be fully prepared for any complications in such cases. All three patients were diagnosed and referred for treatment without delay.
Two of our patients (cases 1 and 2) were receiving the proton pump inhibitor (PPI) pantoprazole in combination with aspirin and clopidogrel. It has been proposed that PPIs and clopidogrel may interact pharmacologically due to their shared metabolism via the cytochrome P450 (CYP450) enzyme system. Among PPIs, omeprazole is considered to have a high potential for interaction with clopidogrel, whereas pantoprazole is thought to have a relatively low interaction potential [14]. Nonetheless, despite its lower interaction risk, pantoprazole may still have contributed to an altered bleeding risk during EBB. No other CPY450-metabolism dependent medications were reported.
It is important to note that all procedures were performed using a Fujinon Fujifilm EB-530T flexible bronchoscope in conjunction with Micro-Tech (Nanjing) biopsy forceps (1.8 mm diameter, 2.0 mm working channel, 120 cm working length).
Although it is generally advised to stop clopidogrel 5–7 days before the procedure, early diagnosis and treatment are critical in some cases. In such situations, where the benefits may outweigh the risks, EBB may be performed after taking all necessary precautions. Based on our case reports, we hope to encourage further prospective studies and the development of new guidelines on the subject, particularly regarding EBB in patients on DAPT.
The limitations of our case series include its retrospective design, the very small sample size, and the potential presence of drug–drug interactions that may have influenced bleeding outcomes during EBB.