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Journal of Bronchology & Interventional Pulmonology:
doi: 10.1097/LBR.0b013e3182720428
Original Investigations

Effect of Routine Clopidogrel Use on Bleeding Complications After Ultrasound-guided Thoracentesis

Zalt, Mohammad B. MD*,†; Bechara, Rabih I. MD*,†; Parks, Christopher MD*,†; Berkowitz, David M. MD*,†

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Author Information

*Emory University School of Medicine, Atlanta

Cancer Treatment Centers of America, Southeastern Regional Medical Center, Newnan, GA

Disclosure: There is no conflict of interest or other disclosures.

Reprints: Mohammad B. Zalt, MD, Emory Clinic, Bldg A, 4th floor Pulmonary, 1365 Clifton Road, NE, Atlanta, GA 30322 (e-mails: mohammad.b.zalt@emory.edu; bacharzalt@gmail.com).

Received May 6, 2012

Accepted August 27, 2012

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Abstract

Background: Thoracentesis is one of the most commonly performed medical procedures with an excellent safety profile. Clopidogrel (a compound that inhibits adenosine diphosphate–induced platelet aggregation) is often prescribed for primary or secondary prevention of cardiovascular disease and has been associated with bleeding complications in patients undergoing surgical procedures. The purpose of this study was to assess the safety of ultrasound (US)-guided thoracentesis in patients receiving clopidogrel therapy.

Methods: Data were collected on 30 consecutive patients taking clopidogrel without other known underlying coagulation problems. These patients underwent 45 US-guided thoracenteses over 26 months. Clopidogrel was not discontinued before the thoracentesis in patients presenting with symptomatic pleural effusion. Thoracenteses were performed in these patients and the incidence of bleeding and other complications among patients was reported.

Results: Between June 2009 and August 2011, there were 30 consecutive patients on clopidogrel at the time of thoracenteses. These patients presented with respiratory distress because of pleural effusion and underwent a total of 45 thoracenteses. There was no significant bleeding or other complications in this patient population. No patient required transfusion after the procedure.

Conclusion: Patients who are receiving clopidogrel and present with symptomatic pleural effusion can safely undergo US-guided thoracentesis without interrupting clopidogrel before the procedure. Larger studies are required to confirm these results.

Thoracentesis is one of the most commonly performed medical procedures with an excellent safety profile and few contraindications. Patients often present with shortness of breath, but may even have respiratory distress secondary to the pleural effusion. In these patients, drainage of pleural fluid can prevent respiratory failure. Some of these patients may be taking clopidogrel at the time of thoracentesis.

Clopidogrel (Bristol-Myers Sqibb, New York, NY) is a thienopyridine compound that inhibits adenosine diphosphate–induced platelet aggregation.1 It has been shown to prevent thrombosis in patients with acute coronary syndrome, coronary artery stenting, and cardiovascular disease.2,3 Several studies have shown that withdrawing clopidogrel therapy in patients who have undergone placement of drug-eluting stent implantation can be associated with a marked increase in the risk of coronary thrombosis (29%).4 As such, the recent recommendation from the American Heart Association’s Science Advisory Committee is that patients who have undergone placement of a drug-eluting coronary artery stent should continue to receive dual antiplatelet therapy for at least 12 months.5,6 As a result, physicians are often faced with the challenge of performing thoracentesis with an increased risk of bleeding in an effort to prevent respiratory failure versus delaying pleural fluid drainage while clopidogrel is being held for 5 to 7 days.

Currently, there are no data on the effect of clopidogrel on the risk of bleeding during ultrasound (US)-guided thoracentesis. In our study, we sought to determine whether clopidogrel increased the risk of bleeding during and after US-guided thoracentesis in patients requiring an emergent intervention.

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PATIENTS AND METHODS

The study was approved by the Institutional Review Board (# 00046825) and all patients provided written informed consent to the US-guided thoracenteses. The study was carried out prospectively.

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Study Population

Patients undergoing US-guided thoracenteses between June 2009 and August 2011 were evaluated. Patients eligible for inclusion in our study were older than 18 years, presenting with respiratory distress secondary to pleural effusion, taking clopidogrel until the day of the procedure, and had no known underlying coagulation problems (Table 1).

Table 1
Table 1
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Patients taking clopidogrel who presented with pleural effusion with no associated respiratory distress were excluded. In these patients, clopidogrel was held for 5 to 7 days before the procedure. The mean age of the patients who underwent thoracentesis while on clopidogrel was 75.5 years (range, 41 to 96 y); 30% were men. All patients in our study had platelets count greater than 100,000 and an international normalized ratio <1.5 before the procedure. The mean respiratory rate of our patients before the procedure was 25 breaths per minute and the oxygen saturations were above 90%. Most patients were already on an O2 supplement at the time of the procedure. The baseline demographic data are presented in Table 2.

Table 2
Table 2
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Use of Clopidogrel

The indication for dose and frequency for clopidogrel use were determined just before the procedure. US-guided thoracentesis was then performed.

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US-guided Thoracentesis

All procedures were performed by the interventional pulmonary (IP) attendings and IP fellows. US guidance (Sonosite, Bothel, WA) was used in all procedures to confirm the pleural effusion, assess its size, and determine the optimal puncture site. A curvilinear transducer (5 MHz) was used. Thoracenteses were performed using the “Arrow Thoracentesis Tray” (Arrow International Inc., Reading, PA) after the standard technique.7 The area surrounding the puncture site was sterilized with chlorhexidine before the placement of sterile drape. Once the puncture site and surrounding skin were sterilized, a local anesthetic with 1% lidocaine was administered. A small incision was then made at the insertion site using a No.11 scalpel blade. While applying gentle aspiration, the thoracentesis catheter over needle assembly was advanced toward the rib, and then walked over the superior edge of the rib into the pleural cavity. The catheter was then advanced over the needle into the pleural space and the needle was removed. The pleural fluid was drained using the manual syringe pump method. The pleural pressures were measured routinely in all patients using the simple water manometer technique. The operators performing the procedure documented the incidence and intensity of any bleeding during or after the procedure. All patients were observed in the postoperative unit for 60 minutes before discharge.

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Statistical Analysis

All values are presented as means, numbers, or percentages.

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RESULTS

Thirty patients receiving clopidogrel and presenting with respiratory distress secondary to pleural effusion were included in this study. All patients used clopidogrel within 24 hours of the procedure and continued using it daily after the procedure. The most common indication for using clopidogrel was primary and secondary prevention of coronary thrombosis and prevention of graft occlusion after CABG (93%) (Table 2). The indication for US-guided thoracentesis was new-onset pleural effusion in 30 procedures and recurrent pleural effusion in 15 procedures. The mean amount of fluids drained was 1367 mL. The causes of pleural effusions are shown in (Table 3). No pneumothoraces occurred as a result of US-guided thoracentesis.

Table 3
Table 3
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Only 1 patient (2.22%) developed procedure-related bleeding in the form of a small subcutaneous hematoma at the puncture site. Hemostasis was achieved by applying pressure to the area and the patient was discharged from the postoperative unit in a stable condition. A postprocedure complete blood count in this patient showed no significant decrease in hemoglobin (Hb). In this cohort, there were no deaths, need for blood transfusions, or admissions to the critical care unit secondary to procedure-related complications.

All patients in this study completed postprocedure chest x-rays within 72 hours obtained by the referring physicians for various reasons including reassessment of pleural effusion. All studies indicated a decrease in the size of effusion. None of the follow-up chest radiographs showed worsening effusion suggestive of intrapleural hemorrhage.

Complete blood counts were obtained by the referring physicians in all patients within 48 hours after the procedure for various reasons. In 1 patient, the Hb decreased by 3 g 24 hours after the procedure and then stabilized without blood transfusion. Although the cause of the decrease in Hb in this patient could not be determined by the primary team, it was not attributed to the thoracentesis as the postprocedure follow-up chest radiographs failed to show evidence of pleural fluid reaccumulation and there was no clinical evidence of hematoma. Otherwise, there was no significant decrease in the Hb (0 to 1.5 g/dL) in our study population.

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DISCUSSION

Thoracentesis is one of the most commonly performed medical procedures with an excellent safety profile and few contraindications. Pulmonologists frequently encounter patients receiving clopidogrel who require diagnostic or therapeutic thoracentesis. In this study, we found that thoracentesis performed in patients receiving clopidogrel and presenting with respiratory distress secondary to pleural effusion carries a low risk of complications.

Previous studies have shown that in patients presenting with acute coronary artery syndrome without ST-segment elevation, the rate of major bleeding complications [gastrointestinal (GI) bleeding and bleeding at the sites of arterial punctures] associated with clopidogrel therapy was higher than that with aspirin alone (relative risk, 1.38).2 In addition, there is a significant risk of bleeding from a transbronchial lung biopsy in patients on clopidogrel.8 Accordingly, patients are often advised to discontinue the use of clopidogrel several days before invasive procedures to reduce the risk of bleeding. Several reports have shown that withdrawing clopidogrel therapy in patients who underwent placement of drug-eluting stent can be associated with a marked increase in the risk of coronary thrombosis (29%).4 In fact, withdrawal of clopidogrel has been shown to have a rebound effect, with an increase in the hypercoagulation and prothrombotic state.4,9 Thus, the recent recommendation from the American Heart Association’s Science Advisory Committee is that patients who have undergone placement of a drug-eluting coronary artery stent should continue to receive dual antiplatelet therapy for at least 12 months.5,6 In a recent prospective multicenter, observational cohort study of 1134 patients with coronary stents, the rate of major adverse cardiac and cerebrovascular events and major or minor bleeding complications in coronary stented patients undergoing urgent or planned noncardiac surgery (GI endoscopy, GI surgery, orthopedic, urology) was evaluated.10 In this study, the major adverse cardiac and cerebrovascular events were observed in 10.9% of patients within an average time delay from the invasive procedure to event of 3.3 to 5.3 days. Interruption of oral antiplatelet therapy more than 5 days before an invasive procedure was the key independent perioperative risk for myocardial infarction and stent thrombosis.

Several studies have shown that the rate of major bleeding complications (GI bleeding and bleeding at the sites of arterial punctures) associated with clopidogrel therapy was higher than that with aspirin alone.2,8 Patients are often advised to discontinue the use of clopidogrel several days before invasive procedures to reduce the risk of bleeding. Clopidogrel use had considerably increased the risk of bleeding after a transbronchial lung biopsy.8 Ernst et al8 reported that patients on clopidogrel had an 89% rate of bleeding after a transbronchial lung biopsy compared with a rate of 3.4% in the control group. More recently, the safety of clopidogrel use in EBUS-TBNA was evaluated by Stather and colleagues in a retrospective review of 12 cases.11 The authors reported no significant bleeding. Recent data show that thoracotomy can be performed safely in patients taking clopidogrel.12

Our study has 3 major limitations: our population was small, the study is a single-center experience, and all thoracenteses were carried out/supervised by highly experienced operators. We hope to validate the results of this investigation with a larger scale, multicenter trial. In addition, the safety of performing thoracentesis in patients on clopidogrel may not be extrapolated to less experienced operators.

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CONCLUSIONS

In patients receiving clopidogrel and presenting with symptomatic pleural effusion, withholding clopidogrel for 5 to 7 days before US-guided thoracentesis is not necessary as the risk of bleeding is low. Further research and experience in larger studies is required to confirm the result of our study.

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ACKNOWLEDGMENT

The authors thank Cicely Ross, RRT/PFT, the Emory Clinic, NP-s Emory University, for her significant contribution to our study in the collection and organization of the data.

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REFERENCES

1. Verstraete M, Zoldheyi P. Novel antithrombotic drugs in development. Drugs. 1995;49:856–884

2. Yusuf S, Zhao F, Mehta Sr, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502

3. Moussa I, Oetgen M, Roubin G, et al. Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation. Circulation. 1999;99:2364–2366

4. Lakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug eluting stent. JAMA. 2005;293:2126–2130

5. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007;115:813–818

6. Kim DH, Daskalakis C, Ilvestry SC, et al. Aspirin and clopidogrel use in the early postoperative period following on-pump and off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2009;138:1377–1384

7. Dimov V, Altaqi B Thoracentesis: a step-by-step procedure guide with photos. Clinical notes. Available at http://note3.blogspot.com/2004/02/thoracentesisprocedure-guide.html. Accessed May 11, 2005

8. Ernst A, Eberhardt R, Wahidi M, et al. Effect of routine clopidogrel use on bleeding complications after transbronchial biopsy in humans. Chest. 2006;129:734–737

9. Newsome LT, Weller RS, Gerancher JC, et al. Coronary artery stents. II: perioperative considerations and management. Anesth Analg. 2008;107:570–590

10. Albaladejo P, Marret E, Samama C-M, et al. Non-cardiac surgery in patients with coronary stents: the RECO study. Heart. 2011;97:1566–1572

11. Stather DR, MacEachern P, Chee A, et al. Safety of endobronchial ultrasound-guided transbronchial needle aspiration for patients taking clopidogrel: a report of 12 consecutive cases. Respiration. 2012;83:330–334

12. Certfolio RJ, Minnich DJ, Brayant AS, et al. General thoracic surgery is safe in patients taking clopidogrel (plavix). J Thorac Cardiovasc Surg. 2012;140:970–976

Keywords:

antiplatelet; bleeding; clopidogrel; pleural effusion; ultrasound; thoracentesis.

© 2012 Lippincott Williams & Wilkins, Inc.

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