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Erie, PA
Dr. Chinsky practices with Chest Diseases of Northwestern Pennsylvania, Erie, PA.
Correspondence to: Kenneth Chinsky, MD, FCCP, 3580 Peach St, Suite 103A, Erie, PA 16508; e-mail: lchinsky{at}aol.com
Few situations elevate the BP or tighten the sphincter tone of a pulmonologist more than bleeding after transbronchial biopsy (TBB). One or two drops of blood mixed with a small volume of sputum appear through the bronchoscope to be a raging river. We all know the drill: occlude the bleeding orifice and wait. And wait. Suction a bit, but don’t disturb the forming clot. And wait.
Some of you may have learned a few tricks along the way. One mentor advocated instilling a little topical epinephrine to stem the tide (where is the evidence-based medicine proving the efficacy of that technique?). Others tamponade the offending orifice by inflating the balloon of a pulmonary artery catheter or Fogarty catheter. Rarely, surgical control of bleeding via thoracotomy is necessary. Fortunately, the old adage "all bleeding eventually stops" usually holds true.
The key is prevention by choosing appropriate candidates for TBB. Does the patient have a history of bleeding after other procedures? Are they thrombocytopenic? Is there uremic platelet dysfunction? Despite our best efforts, serious bleeding occasionally occurs after TBB, invariably after that one final biopsy!
As a physician in private practice, I enjoy the academic exercise involved in critically reviewing original manuscripts for CHEST. I particularly look forward to the studies that address clinical questions I have encountered in my everyday work. Recently, my partner had a patient receiving clopidogrel who had a massive hemorrhage after TBB. Although the patient recovered, my partner was distraught, wondering if he had missed something and if clopidogrel had contributed to the bleeding. Despite an extensive literature search, he found very little data that addressed his concerns, and no human data specifically looking at the risk of TBB in patients receiving this medication. There are some data, however, about bleeding complications during other procedures in patients receiving clopidogrel. For example, preoperative use of clopidogrel with aspirin was associated with increased need for blood products after coronary artery bypass grafting.1 Data such as these concerning bleeding complications after other procedures may not necessarily be applicable to TBB. The most obvious issue is that the bleeding site is neither directly visible nor compressible.
Imagine my delight when coincidentally the study by Wahidi et al2 arrived for me to review just days later. They also reviewed studies about bleeding complications during other procedures in patients receiving clopidogrel and observed, as had my partner, that there are no data directly addressing the safety of TBB in patients receiving this medication. Their study employed a porcine model and demonstrated the absence of significant bleeding after TBB in animals administered clopidogrel with or without aspirin. While animal models are not always directly applicable to humans, there are significant similarities between the coagulation system and lung anatomy of pigs and humans. This represents an excellent first step to answering the clinical question, but there are limitations to their conclusions. First, they admit that studies done on healthy pigs may not apply to ill humans. Second, there were a relatively small number of animals, and no serious bleeding was observed in any instance.
I agree with the authors that ideally the next step would be human studies. Practically speaking, it would be difficult simply to randomize patients receiving clopidogrel undergoing TBB to continue or hold this medication before the procedure. As with other anticoagulants, there are ethical concerns given the risk for thrombosis when medication is held for a time before the procedure.3 There are many potential confounding variables that would need to be reconciled. Also, although clopidogrel is commonly used, it would still likely require a multicenter study to accumulate enough patients to answer the question. Another option might be a registry of patients receiving this medication, documenting bleeding complications of any invasive procedure. Though statistical and methodologic issues exist with this approach, the incidence of bleeding could be compared to historical data. Given the implications, the pharmaceutical industry might be willing to sponsor such a registry.
Discussion of the treatment of bleeding after bronchoscopy was beyond the scope of the current study. Although a number of techniques exist, again there is a dearth of evidence about specific interventions proven beneficial in controlled studies. Studies are difficult to interpret because some do not differentiate between risks of endobronchial biopsy compared to TBB. Some advocate use of vasopressin before invasive procedures to improve uremic platelet dysfunction in those with renal failure.4 A review5 of the Cleveland Clinic experience discussed use of intrabronchial epinephrine with decubitus positioning of the bleeding hemithorax, balloon tamponade, bronchial artery embolization, and Nd-YAG laser photoresection to control hemorrhage. Others place a temporary bronchus blocker and apply a fibrin sealant6 or use cold saline solution bronchial wash.7
In the absence of human studies looking at the bleeding risk in patients receiving clopidogrel who undergo TBB, what is the next best option? Today there is a lot of attention given to the concept of evidence-based medicine. Nevertheless, the reality remains there are certain clinical questions for which no such evidence currently exists. A recent report8 in CHEST addressed advances and limitations of evidence-based medicine in the ICU and noted that when randomized clinical trials have not been done in a particular field of interest, other evidence, including expert opinion, can be used to treat individual patients. A well-known pulmonary textbook9 discusses uremia, cirrhosis with portal hypertension, severe anemia, underlying bleeding disorders, thrombocytopenia, and platelet dysfunction as risk factors for hemorrhage and potential contraindications to bronchoscopy, but makes no mention of avoidance of any specific medications. Shure10 believed mechanical ventilation and pulmonary hypertension also increased the risk for bleeding after TBB. Immunosuppressed hosts and those with a thoracic malignancy represent other potential at-risk groups.5
In the absence of a definitive answer, it is reasonable to extrapolate from analogous human studies as well as animal data. A study of 285 patients who had received aspirin within 24 h prior to TBB found that the risk of severe bleeding after TBB was < 1% and that compared to a control group, aspirin alone was not found to increase bleeding complications.6 Another porcine model suggested elevation of the international normalized ratio in animals receiving warfarin did not increase bleeding risk after TBB.11 In that study, even with international normalized ratio levels > 10, no hemorrhagic complications developed following TBB.
As physicians we adhere to the principle, "first, do no harm." Despite evidence to the contrary, we cannot seem to get past the emotional roadblock that suggests patients receiving anticoagulation will experience severe bleeding after TBB. This was addressed in a CHEST editorial 5 years ago,12 and I have not seen any change in this prejudice since. However at this time, barring any human studies, it seems reasonable to perform TBB in patients receiving clopidogrel when the clinical situation dictates the procedure is appropriate.
We are not simply technicians performing a minor intervention. It goes without saying that we should perform a thorough history and physical before bronchoscopy. Hopefully, if we choose patients wisely for this procedure, serious bleeding complications can be minimized. Regardless, there appears to be a small yet inescapable baseline hemorrhagic rate that is more related to technical rather than hemostatic issues, and the fact remains the majority of bleeding events after bronchoscopy occur in patients with normal coagulation parameters.11 What Flick13 stated almost 30 years ago still holds true today: when life-threatening bleeding occurs in a patient without an underlying coagulopathy, it often results from the unpredictable biopsy of a sizeable pulmonary or bronchial artery.
Acknowledgements
I would like to thank Dr. John T. Schaaf for his review of this article.
References
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