2012 - Etiology and Evaluation of Hemoptysis in Adults

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©2012 UpToDate®

AuthorSteven E Weinberger, MD

Section EditorPraveen N Mathur, MB, BS

Deputy EditorHelen Hollingsworth, MD

Etiology and evaluation of hemoptysis in adults

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jun 2012. | This topic last updated: Abr 3, 2012.

INTRODUCTION — Hemoptysis, or the expectoration of blood, can range from blood-streaking of sputum to thepresence of gross blood in the absence of any accompanying sputum. The term massive hemoptysis isreserved for bleeding that is potentially acutely life-threatening; it has been defined by a number of differentcriteria, often ranging from more than 100 to more than 600 mL of blood over a 24 hour period [1].

The evaluation of hemoptysis that is not immediately life-threatening will be reviewed here. The acute evaluationand management of massive hemoptysis is discussed separately. (See "Massive hemoptysis: Initialmanagement" and "Overview of massive hemoptysis".)

VASCULAR ORIGIN OF HEMOPTYSIS — Blood traversing the lungs can arrive from one of two sites –pulmonary arteries or bronchial arteries. Virtually the entire cardiac output courses through the low-pressurepulmonary arteries and arterioles en route to being oxygenated in the pulmonary capillary bed. In contrast, thebronchial arteries are under much higher systemic pressure but carry only a small portion of the cardiac output.There are generally one or two bronchial arteries for each lung, typically arising from the aorta and lesscommonly from the intercostal arteries. These vessels provide the nutritive blood supply to the airways, hilarlymph nodes, visceral pleura, and some portions of the mediastinum [2].

Despite the quantitatively smaller contribution of the bronchial circulation to pulmonary blood flow, the bronchialarteries are generally a more important source of hemoptysis than the pulmonary circulation. In addition to beingperfused at a higher pressure, they also supply blood to the airways and to lesions within the airways. In somecircumstances, such as bronchiectasis, the bronchial circulation becomes hyperplastic and tortuous, and can bea source of massive hemoptysis.

DIFFERENTIAL DIAGNOSIS OF HEMOPTYSIS — Although the term hemoptysis typically refers toexpectoration of blood originating from the lower respiratory tract, it must be recognized that blood from theupper respiratory tract and the upper gastrointestinal tract can be expectorated and can mimic blood comingfrom the lower respiratory tract.

Blood originating from below the vocal cords can best be categorized according to the site of bleeding.Bronchitis, bronchogenic carcinoma, and bronchiectasis are the most common causes of hemoptysis dependingupon the patient population studied (table 1) [3-5].

Airways diseases — The most common source of hemoptysis is airways disease. Pathologic processesaffecting the airways that can lead to hemoptysis include the following disorders:

Inflammatory diseases, such as bronchitis (either acute or chronic) or bronchiectasis. Even thoughbronchiectasis is typically associated with frequent cough and copious sputum production, the clinicalmanifestations may be more subtle, particularly in those patients with "dry" bronchiectasis.

Neoplasms, including primary bronchogenic carcinoma, endobronchial metastatic carcinoma (mostcommonly from melanoma or from breast, colon, or renal cell carcinoma), or bronchial carcinoid.Bronchial carcinoid, a highly vascular tumor that is unrelated to smoking, should be considered in a youngor middle-aged nonsmoker with recurrent hemoptysis. In patients with AIDS, Kaposi's sarcoma involving

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the airways (and/or the pulmonary parenchyma) is a potential cause of hemoptysis [6]. (See "Bronchialcarcinoid tumors" and "Pulmonary involvement in HIV-associated Kaposi's sarcoma".)

Foreign body. (See "Airway foreign bodies in adults".)

Airway trauma.

Fistula formation between a vessel and the tracheobronchial tree. Although an uncommon cause ofhemoptysis, fistulas between the aorta and the airway (especially the left bronchopulmonary tree) arefrequently associated with aneurysms of the thoracic aorta and are fatal if not diagnosed and surgicallytreated [7]. Tracheo-innominate fistulas are a rare but potentially life-threatening complication oftracheostomy, occurring most often if the tracheostomy tube is placed too low [8]. The tube can erodedirectly into the innominate artery, which crosses the anterolateral surface of the trachea at the level of theupper sternum.

A superficial, subepithelial bronchial artery contiguous with the bronchial mucosa (Dieulafoy's disease)[9,10].

Pulmonary parenchymal diseases — Causes of bleeding originating from the pulmonary parenchyma fall intoseveral major categories:

Infection, especially tuberculosis, pneumonia, aspergilloma, and lung abscess. Hemoptysis, which can belife-threatening, complicates the course of 50 to 85 percent of patients with an aspergilloma [11,12]. (See"Clinical manifestations and diagnosis of chronic pulmonary aspergillosis".)

Inflammatory or immune disorders, including Goodpasture's syndrome, idiopathic pulmonaryhemosiderosis, lupus pneumonitis, and granulomatosis with polyangiitis (Wegener’s). (See "Differentialdiagnosis and evaluation of glomerular disease", section on 'Acute glomerulonephritis and pulmonaryhemorrhage' and "Idiopathic pulmonary hemosiderosis" and "Pulmonary manifestations of systemic lupuserythematosus in adults".)

A genetic defect of connective tissue, specifically Ehlers-Danlos syndrome, vascular type [13].

A coagulopathy, such as thrombocytopenia or use of anticoagulants [14].

Iatrogenic, especially due to either percutaneous or transbronchial lung biopsy. Hemoptysis, which isusually minor and transient, occurs in 5 to 10 percent of percutaneous lung biopsies, but massivehemorrhage and death have also been reported [15]. In a nine year series of patients who underwentfiberoptic bronchoscopy, bleeding was reported to complicate the subgroup that had transbronchial,endobronchial, or brush biopsy with a frequency of approximately 2 percent [16].

Miscellaneous causes of pulmonary parenchymal hemorrhage that should be considered in the appropriateclinical setting include the following:

Cocaine-induced pulmonary hemorrhage. Hemoptysis has been described in 6 percent of habitualsmokers of free-base cocaine ("crack") and has been associated with diffuse alveolar hemorrhage [17-19].Although the mechanism for bleeding is not known, possibilities include pulmonary vasoconstriction withanoxic damage to epithelial and/or endothelial cells, and direct toxicity of the inhaled substances onalveolar epithelial cells [19]. (See "Pulmonary complications of cocaine abuse".)

Catamenial hemoptysis, characterized by hemoptysis that is recurrent and coincident with menses. Thecause is intrathoracic endometriosis, usually involving the pulmonary parenchyma but occasionallyaffecting the airways [20-22]. (See "Thoracic endometriosis".)

Bevacizumab treatment. Hemoptysis, ranging from minor to life-threatening, has been reported with theuse of the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab [23,24]. Although themechanism is uncertain, it may be related to destruction of tissue as a result of VEGF inhibition,particularly in the setting of a cavitating lung cancer.


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Nitrogen dioxide exposure in indoor ice arenas. Hemoptysis has been reported in ice hockey playersexposed to high levels of nitrogen dioxide created by malfunctioning propane-powered ice surfacingequipment and inadequate ventilation [25,26]. Among 16 hockey players who developed cough afterexposure to a faulty resurfacer, 92 percent reported dyspnea, 75 percent chest pain, and 33 percenthemoptysis [27]. Some but not all of the reported patients had radiographic pulmonary parenchymalopacities [25-27].

Pulmonary vascular disorders — Although this category overlaps with pulmonary parenchymal disease, thedisorders mentioned below are those in which the primary pathology is intrinsic to the pulmonary vasculature oraffects the pressure within these vessels.

Pulmonary embolism. (See "Diagnosis of acute pulmonary embolism".)

Pulmonary arteriovenous malformation, either with or without underlying Osler-Weber-Rendu syndrome.(See "Pulmonary arteriovenous malformations: Epidemiology, etiology, pathology, and clinical features".)

Elevated pulmonary capillary pressure, as seen with mitral stenosis or significant left ventricular failure.

Iatrogenic, primarily resulting from pulmonary artery perforation from a Swan-Ganz catheter. Although thisis a rare complication, it can be associated with massive bleeding and death [28]. (See "Pulmonary arterycatheterization: Indications and complications".)

Cryptogenic — Depending upon the study, up to 30 percent of patients with hemoptysis have no causeidentified even after careful evaluation including bronchoscopy. These patients are classified as having eithercryptogenic or idiopathic hemoptysis [9,29-31].

In one series of 67 patients with cryptogenic hemoptysis, the prognosis was generally good, and most patientshad resolution of bleeding within six months of evaluation [29]. Another series found that 7 of 115 patients withcryptogenic hemoptysis were subsequently diagnosed with lung cancer over a mean follow-up period of 6.6years [30]. A third retrospective series stressed the finding of a superficial bronchial artery beneath the bronchialepithelium (Dieulafoy's disease) in a subset in patients with cryptogenic hemoptysis who required surgery formassive hemoptysis [9].

EVALUATION OF HEMOPTYSIS — Besides history and physical examination, the initial important study forevaluating the patient with hemoptysis is the chest radiograph. Abnormal findings may be suggestive of a varietyof specific causes of hemoptysis, ranging from neoplasm to focal infection (tuberculosis, aspergilloma) to mitralstenosis.

Useful laboratory studies include measurement of hematocrit (to assess the magnitude and chronicity ofbleeding), urinalysis and renal function (in those circumstances in which a pulmonary-renal syndrome such asGoodpasture's syndrome or granulomatosis with polyangiitis (Wegener’s) might be responsible for bleeding),and a coagulation profile (to exclude thrombocytopenia or another coagulopathy as a contributing factor).

Adequacy of oxygenation is assessed with pulse oximetry or arterial blood gas analysis. Evaluation forpulmonary embolism should be considered in patients with risk factors for pulmonary embolism and abnormalgas transfer. (See "Diagnosis of acute pulmonary embolism".)

Further evaluation is next directed toward confirming the suspected diagnosis if the history, physicalexamination, or any of the above studies suggests a particular cause for the hemoptysis. Fiberopticbronchoscopy is a particularly useful procedure, often allowing localization of the site of hemoptysis andvisualization of endobronchial pathology causing the bleeding.

Additional issues that arise in evaluating the patient with hemoptysis relate to the use of flexible bronchoscopy:its role in patients with normal chest radiographs, the optimal timing of the procedure, and the relative roles offiberoptic bronchoscopy and high-resolution CT scanning (HRCT) [32]. (See "High resolution computedtomography of the lungs".)

Flexible bronchoscopy in patients with a normal chest radiograph — Flexible bronchoscopy is oftenconsidered in patients with hemoptysis and a normal or nonlocalizing chest radiograph to rule out endobronchial


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malignancy that is radiographically silent. However, in such patients, the likelihood of finding a tumor by flexiblebronchoscopy is generally less than 5 percent [33-37]. Risk factors predicting those individuals most likely tohave tumor found on bronchoscopy include [34,35,37]:

Male sex

Older age, greater than 50 years in one study [35], greater than 40 years in another [37]

Smoking history greater than 40 pack years

Duration of hemoptysis greater than one week [34]

Optimal timing of flexible bronchoscopy — In a retrospective study, flexible bronchoscopy performed acutely(during hemoptysis or within 48 hours after hemoptysis stopped) was more likely to visualize active bleeding (41versus 8 percent) or its site (34 versus 11 percent) than delayed bronchoscopy [38]. However, the clinicaloutcome was not significantly different between the early and delayed groups.

Flexible bronchoscopy versus HRCT — Flexible bronchoscopy and HRCT are, in many ways, complementarystudies, each with specific advantages in certain clinical situations [5,32]. In one study of 91 patients withhemoptysis, for example, HRCT demonstrated all tumors seen by bronchoscopy as well as several which werebeyond bronchoscopic range [39]. On the other hand, HRCT could not detect bronchitis or subtle mucosalabnormalities which could be seen by bronchoscopy. In another report of 57 patients, HRCT was particularlyuseful in diagnosing bronchiectasis and aspergillomas, while bronchoscopy was diagnostic of bronchitis andmucosal lesions such as Kaposi's sarcoma [40].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and

“Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th gradereading level, and they answer the four or five key questions a patient might have about a given condition. Thesearticles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyondthe Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written

at the 10th to 12th grade reading level and are best for patients who want in-depth information and arecomfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail thesetopics to your patients. (You can also locate patient education articles on a variety of subjects by searching on“patient info” and the keyword(s) of interest.)

Basics topic (see "Patient information: Coughing up blood (The Basics)")

SUMMARY AND RECOMMENDATIONS — Hemoptysis may be caused by airways disease (most common),pulmonary parenchymal disease, or pulmonary vascular disease (table 1). (See 'Differential diagnosis ofhemoptysis' above.)

Although there is a trend toward recommending earlier use of HRCT in the investigation of hemoptysis, therelative utility of bronchoscopy and HRCT as the initial diagnostic procedure following chest radiography remainscontroversial. Based upon present data and common practices, we recommend the following approach:

The evaluation should begin with the initial history and physical examination supplemented by chestradiograph and assessment of oxygenation. Important features of the history include age, smoking history,duration and quantity of hemoptysis, and association with symptoms of acute bronchitis or an acuteexacerbation of chronic bronchitis (change in sputum, blood streaking superimposed upon purulentsputum). In addition, it is important to seek information on history or physical examination to suggesteither an upper airway or a gastrointestinal source for the bleeding. (See 'Evaluation ofhemoptysis' above.)

Additional studies which may be useful depending upon the particular clinical situation include hematocrit,urinalysis, blood urea nitrogen and plasma creatinine concentration, a coagulation profile, and collectionof sputum for cytologic and microbiologic studies. (See 'Evaluation of hemoptysis' above.)


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No immediate further work-up is indicated if the clinical picture is not suggestive of carcinoma (negativechest radiograph, age less than 40 years, no smoking history, and hemoptysis less than 1 week duration),but is suggestive of acute bronchitis (blood streaking superimposed upon purulent sputum). Such apatient should be treated for bronchitis and observed for recurrence of hemoptysis following improvementin purulent sputum production. (See 'Evaluation of hemoptysis' above.)

Further evaluation is indicated if the patient has any of the above risk factors for carcinoma or if thehemoptysis did not occur in the setting of acute bronchitis. Bronchoscopy is the preferred next procedurein those patients with risk factors for tumor or chronic bronchitis (particularly smoking). On the other hand,HRCT is the preferred next procedure in patients at lower risk for tumor or chronic bronchitis but with ahistory or radiograph suggestive of bronchiectasis or an arteriovenous malformation. (See 'Flexiblebronchoscopy versus HRCT' above.)

If hemoptysis persists and the initial procedure (either bronchoscopy or HRCT) is negative, then the otherof these two procedures should be performed. (See 'Flexible bronchoscopy versus HRCT' above.)

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GRAPHICS

Differential diagnosis of hemoptysis

Airway disease

Acute or chronic bronchitis

Airway trauma

Bronchiectasis

Bronchovascular fistulae

Dieulafoy's disease (superficial, subepithelial bronchial artery)

Foreign bodies

Neoplasms

Pulmonary parenchymal disease

Genetic defect in connective tissue (Ehlers-Danlos vascular type)

Infection (especially tuberculosis, pneumonia, mycetoma, or lung abscess)

Inflammatory or immune disorders (eg, granulomatosis with polyangiitis [Wegener’s],

Goodpasture's syndrome, idiopathic pulmonary hemosiderosis, lupus pneumonitis)

Pulmonary vascular disorders

Left atrial hypertension (eg, mitral valve disease, poor left ventricular performance)

Pulmonary arteriovenous malformations

Pulmonary thromboembolism

Miscellaneous

Bevacizumab treatment

Catamenial hemoptysis

Coagulopathy

Cocaine use

Cryptogenic

Iatrogenic

Nitrogen dioxide toxicity (eg, silo fillers, indoor ice arenas with faulty propane powered

equipment and poor ventilation)


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2012 - Etiology and Evaluation of Hemoptysis in Adults

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