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Etiology of hemoptysis in adults

Etiology of hemoptysis in adults
Literature review current through: Jan 2024.
This topic last updated: Jun 05, 2023.

INTRODUCTION — The term hemoptysis refers to expectoration of blood originating from the lower respiratory tract (ie, from below the vocal cords). Pseudohemoptysis, expectoration of blood that comes from the upper respiratory tract and/or the upper gastrointestinal tract, can mimic hemoptysis.

There are several sources of bleeding within the lung and endobronchial tree that can be responsible for hemoptysis. Causes of life-threatening and non-life-threatening hemoptysis are described here. The diagnostic evaluation and management of hemoptysis are reviewed separately. (See "Evaluation and management of life-threatening hemoptysis" and "Evaluation of nonlife-threatening hemoptysis in adults" and "The diffuse alveolar hemorrhage syndromes".)

BRONCHIAL VERSUS PULMONARY ARTERIAL ORIGINS OF HEMOPTYSIS — Blood supply to the lungs is derived from the pulmonary arteries or the bronchial arteries. Supply from the non-bronchial systemic circulation (eg, aorta, intercostal, coronary, thoracic, axillary, subclavian, and upper and lower inferior phrenic arteries) is an anatomical variant in a small percentage of patients (<5 percent). The pulmonary artery circulation supply is a low-pressure system mostly supplying the lung parenchyma; most episodes of hemoptysis are non-life-threatening and originate from the pulmonary artery circulation. In contrast, the bronchial artery circulation is relatively high-pressure from the systemic circulation mostly supplying the endobronchial tree. Although the bronchial artery circulation is responsible for only 2 percent of the total vascular supply to the lung, bleeding from a bronchial artery is the cause of life-threatening hemoptysis in 90 percent of cases. For this reason, patients with non-resolving life-threatening hemoptysis undergo arterial embolization primarily in the bronchial circulation, and less often in the pulmonary circulation. (See "Evaluation and management of life-threatening hemoptysis", section on 'Arteriography'.)

CAUSES OF NON-LIFE-THREATENING HEMOPTYSIS — Most episodes of hemoptysis are non-life-threatening. There are numerous causes of non-life-threatening bleeding from the lower respiratory tract, which are listed in the table (table 1). The most common causes of non-life-threatening hemoptysis in developed countries are acute bronchitis, bronchiectasis, and bronchial neoplasms (primary or secondary) [1-6]. In a brief report of 606 hemoptysis patients from five Italian hospitals, malignancy (19 percent), pneumonia/lung abscess (19 percent), and bronchiectasis (15 percent) were the most common causes [5]. In contrast, in developing countries, infections due to Mycobacterium tuberculosis and Paragonimus westermani and non-cystic fibrosis (CF)-related bronchiectasis are more common causes [1,7-9].

Airways diseases — Hemoptysis is not an uncommon symptom of pathologic airway processes due to the proximal location of bronchi and their bronchial arterial supply.

Bronchitis and bronchiectasis — Inflammatory diseases, such as bronchitis and bronchiectasis (eg, due to cystic fibrosis, immunodeficiency, and prior pneumonia) are common causes of hemoptysis.

In bronchitis, minor amounts of hemoptysis may be seen during an acute flare but hemoptysis is unusual during the chronic phase. Life-threatening hemoptysis from acute bronchitis is very unusual without additional contributing factors (such as anticoagulation). (See "Acute bronchitis in adults" and "Chronic obstructive pulmonary disease: Diagnosis and staging".)

In bronchiectasis, minor amounts of blood that are mixed with expectorated phlegm (“streaky” in appearance) are commonplace during the chronic phase. Less commonly, larger amounts that appear as bright red blood and clots may occur during an acute flare. In contrast to acute bronchitis, bronchiectasis is a common cause of life-threatening hemoptysis. Non-life-threatening hemoptysis is likely due to the chronic airway inflammation that is characteristic of bronchiectasis, while life-threatening hemoptysis is likely due to rapid bleeding from a ruptured tortuous bronchial artery or from hypertrophied submucosal and peribronchial blood vessels. Because more patients with CF now survive into adulthood, recurrent hemoptysis in CF patients with bronchiectasis is occurring more frequently. (See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

Bronchial neoplasm — Malignant neoplasms such as primary bronchogenic carcinoma, endobronchial metastatic carcinoma (most commonly from melanoma or from breast, colon, or renal cell carcinoma), and bronchial carcinoid can all cause hemoptysis. Non-life-threatening hemoptysis occurs in 7 to 10 percent of patients with lung cancer at the time of presentation and in approximately 20 percent of patients at some time during the course of their illness [10]. The most common clinical pattern of hemoptysis due to lung cancer is intermittent small amounts of hemoptysis lasting more than two weeks. Less commonly, bronchogenic carcinoma causes life-threatening hemoptysis. (See 'Bronchogenic carcinoma' below.)

Bronchial carcinoid, a highly vascular tumor that is unrelated to smoking, should be considered in a young or middle-aged nonsmoker with recurrent hemoptysis. The amount of bleeding is variable. Their highly vascular nature raises concern regarding bleeding with biopsy such that some experts defer to surgical excision rather than bronchoscopic biopsy; however the risk of bleeding may be overestimated [11]. (See "Lung neuroendocrine (carcinoid) tumors: Epidemiology, risk factors, classification, histology, diagnosis, and staging".)

In patients with acquired immunodeficiency syndrome (AIDS), Kaposi sarcoma involving the airways (and/or the pulmonary parenchyma) is also a potential cause of hemoptysis. (See "Lung neuroendocrine (carcinoid) tumors: Epidemiology, risk factors, classification, histology, diagnosis, and staging" and "Pulmonary involvement in AIDS-related Kaposi sarcoma" and 'Bronchogenic carcinoma' below.)

Benign neoplasms such as hemangiomas and adenomas are rare causes of hemoptysis; when hemangioma is suspected, it should not be biopsied since bleeding may be life-threatening. The rare vascular endothelial malignancy, angiosarcoma, can cause diffuse alveolar hemorrhage [12]. (See 'Uncommon etiologies' below and 'Bronchogenic carcinoma' below.)

Other airway diseases

Foreign bodies – Hemoptysis can be caused by direct trauma or local inflammation from an inhaled foreign body (FB). Less commonly hemoptysis can be due to FB-related obstruction that results in a necrotizing pneumonia or focal bronchiectasis. (See "Airway foreign bodies in adults".)

Broncholiths – Erosion of a calcified lymph node into the airway can cause hemoptysis [13]. With the decline in prevalence of tuberculosis this is less common, but in the United States it most commonly occurs due to old histoplasma infection.

Airway infections – Airway mucosal infection with herpes virus [14-16] or fungal species [17-19] can cause hemoptysis, particularly in immunocompromised patients.

Fistulas – Fistula formation between a blood vessel and the tracheobronchial tree can occur when there is chronic vascular inflammation (eg, aortic aneurysm, aortic surgery such as stent placement, aortic infection, or an indwelling vascular device) or airway inflammation (eg, tracheobronchial medical device such as an airway stent). Vascular fistulas are at high risk of causing life-threatening hemoptysis, which is often heralded by smaller non-life threatening episodes of bleeding.(See 'Uncommon etiologies' below.)

Dieulafoy lesion – A Dieulafoy lesion is a dilated aberrant submucosal vessel (superficial, subepithelial bronchial artery lesions contiguous with the bronchial mucosa). Bleeding is more likely to result from such lesions in the gastrointestinal tract, but several case reports describe hemoptysis from airway lesions [20-25]. Bronchoscopically, the lesions appear nodular and are red in color; however, some are subtle but can be seen as abnormal vascular lesions on endobronchial ultrasound or bronchial angiography [25]. Endobronchial biopsy should be avoided due to the risk of causing massive hemoptysis [25]. (See "Causes of upper gastrointestinal bleeding in adults", section on 'Dieulafoy's lesion'.)

Pulmonary parenchymal diseases — Causes of bleeding originating from the pulmonary parenchyma fall into several major categories listed below.

Infection — A number of lung parenchymal infections, especially tuberculosis, mycetoma, lung abscess, and necrotizing pneumonia can cause hemoptysis, most often due to erosion into blood vessels. Hemoptysis from infection can be life-threatening, particularly among patients with an aspergilloma and tuberculosis [26,27]. Among those with aspergilloma, hemoptysis is relatively common, occurring in up to 40 percent of patients in some series. In the developing world, P. westermani is a common cause of hemoptysis, and hemorrhagic dengue fever is associated with hemoptysis in about one-fourth of patients [28]. Hemoptysis is a late manifestation of Ebola virus. It may also occur in some patients with Coronavirus disease-2019 (COVID-19) respiratory infections [29,30]. Other infections are listed in the table (table 1). (See "Pulmonary tuberculosis: Clinical manifestations and complications", section on 'Hemoptysis' and "Chronic pulmonary aspergillosis: Epidemiology, clinical manifestations and diagnosis" and "Lung abscess in adults" and 'Fungal infections' below.)

Other parenchymal diseases

Rheumatic and immune disorders – Rheumatic and immune disorders can all cause non-life-threatening as well as life-threatening hemoptysis. Disorders include anti-glomerular basement membrane (ie, Goodpasture) syndrome, lupus pneumonitis/vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, primary antiphospholipid antibody syndrome, Behçet syndrome, pulmonary capillaritis, and idiopathic pulmonary hemosiderosis. Many of these conditions cause diffuse alveolar hemorrhage, rather than focal bleeding. The degree of alveolar bleeding may not be reflected in the volume of expectorated blood since less coughing may occur. (See "Pulmonary manifestations of systemic lupus erythematosus in adults" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Respiratory tract involvement" and "Idiopathic pulmonary hemosiderosis" and "Clinical manifestations and diagnosis of Behçet syndrome", section on 'Pulmonary disease' and "Glomerular disease: Evaluation and differential diagnosis in adults" and 'Uncommon etiologies' below and "The diffuse alveolar hemorrhage syndromes".)

Genetic disorders of connective tissue – Hemoptysis has been reported as a complication of the vascular type of Ehlers-Danlos syndrome, associated with genetic variants of the collagen type III gene (OMIM 25940258) [31,32]. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes".)

Catamenial hemoptysis – Catamenial hemoptysis is characterized by recurrent hemoptysis that is coincident with menses. The cause is intrathoracic endometriosis, usually involving the pulmonary parenchyma but occasionally affecting the airways [33]. (See "Clinical features, diagnostic approach, and treatment of adults with thoracic endometriosis".)

Pulmonary vascular disorders — Although this category overlaps with pulmonary parenchymal disease, the disorders mentioned below are those in which the primary pathology is intrinsic to the pulmonary vasculature or affects the pressure within these vessels. In many cases hemoptysis can be life-threatening. (See 'Common etiologies' below.)

Elevated pulmonary capillary pressure – Elevated pulmonary venous pressure, as seen with mitral stenosis, congenital heart disease, significant left ventricular failure, pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis, and fibrosing mediastinitis can be associated with hemoptysis. Pulmonary arterial hypertension is a rare cause of hemoptysis. (See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults" and "Rheumatic mitral stenosis: Clinical manifestations and diagnosis", section on 'Hemoptysis' and "Epidemiology, pathogenesis, clinical evaluation, and diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis in adults" and "Mediastinal granuloma and fibrosing mediastinitis", section on 'Clinical presentation' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Symptoms'.)

Pulmonary arteriovenous malformation (PAVM) – Hemoptysis may occur with PAVM (idiopathic or heritable hemorrhagic telangiectasia) and may be life-threatening (eg, during pregnancy). (See "Pulmonary arteriovenous malformations: Epidemiology, etiology, and pathology in adults" and 'Uncommon etiologies' below.)

Pulmonary or bronchial artery aneurysms – Hughes-Stovin syndrome, which may be a variant of Behçet syndrome, is characterized by the presence of multiple pulmonary and/or bronchial aneurysms that can cause life-threatening hemoptysis [34]. (See "Clinical manifestations and diagnosis of Behçet syndrome".)

Pulmonary artery pseudoaneurysms – Pulmonary artery pseudoaneurysms (Rasmussen aneurysm), which are usually caused by infection, neoplasms, or trauma, have a predilection for peripheral pulmonary arteries and may be single or multiple [35]. Active tuberculosis and paragonimiasis may cause sudden rupture of a Rasmussen aneurysm [36,37]. Bleeding is more likely to be life-threatening.

Pulmonary embolism (thrombotic, fat, septic) – Hemoptysis is a rare presenting manifestation of pulmonary embolism and is usually non-life-threatening unless the patient is receiving anticoagulant therapy. The presumed mechanism is pulmonary infarction, which usually occurs with smaller, more distal thromboembolism. (See "Epidemiology and pathogenesis of acute pulmonary embolism in adults", section on 'Clinical presentation, evaluation, and diagnosis' and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

Pulmonary capillaritis – Pulmonary capillaritis due to collagen vascular diseases, for example, may present with hemoptysis due to vessel inflammation. (See "Overview of pleuropulmonary diseases associated with rheumatoid arthritis", section on 'Vasculitis' and "The diffuse alveolar hemorrhage syndromes", section on 'Pulmonary capillaritis'.)

Trauma and bleeding disorders

Bleeding disorders – Bleeding disorders (eg, thrombocytopenia, disseminated intravascular coagulation, platelet dysfunction syndromes, von Willebrand disease) and use of anticoagulant or antiplatelet medications may cause episodes of non-life-threatening or life-threatening hemoptysis [38-40]. Therapeutic anticoagulation is not usually sufficient as a sole explanation for hemoptysis.

Airway or parenchymal trauma – Both penetrating and blunt chest trauma can cause hemoptysis. (See "Initial evaluation and management of blunt thoracic trauma in adults" and "Initial evaluation and management of chest wall trauma in adults".)

Iatrogenic injury – Hemoptysis can result from a variety of medical interventions, especially percutaneous or transbronchial lung biopsy and ablative procedures involving the airway as well as stent placement and balloon dilation procedures. Most cases are non-life-threatening. However, hemoptysis may be life-threatening when patients have a bleeding diathesis. (See "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Bleeding' and "Bronchoscopic cryotechniques in adults", section on 'Complications' and "Endobronchial brachytherapy", section on 'Early' and "Endobronchial photodynamic therapy in the management of airway disease in adults", section on 'Photodynamic therapy specific'.)

Pulmonary artery perforation is a rare complication of pulmonary artery catheter placement, which can be associated with life-threatening bleeding and death. Localized pulmonary infarction with hemoptysis can also occur when a catheter is left in too distal a location or when a balloon is inflated for a prolonged period. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults", section on 'Use and maintenance' and 'Uncommon etiologies' below.)

Hemoptysis has been reported to occur after pulmonary vein isolation using cryoballoon ablation for atrial fibrillation [41-44]. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults", section on 'Use and maintenance' and "Overview of catheter ablation of cardiac arrhythmias", section on 'Cryothermal energy' and "Catheter ablation for the treatment of atrial fibrillation: Technical considerations for non-electrophysiologists", section on 'Pulmonary vein isolation'.)

Miscellaneous — Miscellaneous causes of pulmonary hemorrhage that should be considered in the appropriate clinical setting include the following:

Drugs and toxins:

Cocaine-induced pulmonary hemorrhage – Hemoptysis has been described in 6 percent of habitual smokers of free-base cocaine ("crack") and has also been associated with diffuse alveolar hemorrhage. Levamisole-contaminated cocaine has been associated with pulmonary hemorrhage in several case reports. (See "Pulmonary complications of cocaine use", section on 'Clinical features'.)

Bevacizumab treatment – Hemoptysis, ranging from minor to life-threatening, has been reported with the use of the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab [45,46]. Although the mechanism 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.

Nitrogen dioxide exposure in indoor ice arenas – Hemoptysis has been reported in ice hockey players exposed to high levels of nitrogen dioxide created by malfunctioning propane-powered ice surfacing equipment and inadequate ventilation [47-49].

E-cigarette or vaping product use associated lung injury (EVALI) – In a case series of 53 patients with vaping-associated lung injury, hemoptysis was reported in six patients (11 percent) at the time of presentation [50]. (See "E-cigarette or vaping product use-associated lung injury (EVALI)".)

Other drugs – Other drugs associated with non-life-threatening hemoptysis include riociguat [51], hydralazine (ie, hydralazine-induced vasculitis [52]), and argemone alkaloid-contaminated cooking oil [53].

Miscellaneous and idiopathic:

Idiopathic pulmonary hemosiderosis (see "Idiopathic pulmonary hemosiderosis")

Fibrosing mediastinitis (see "Mediastinal granuloma and fibrosing mediastinitis")

Pulmonary amyloid (see "Overview of amyloidosis", section on 'Pulmonary disease')

CAUSES OF LIFE-THREATENING HEMOPTYSIS

Definition — The term life-threatening hemoptysis (formerly massive hemoptysis) is generally used to describe the expectoration of a large amount of blood and/or a rapid rate of bleeding [8,54-57]; however, the precise thresholds that constitute life-threatening hemoptysis are controversial. We generally prefer to use the term “life-threatening hemoptysis” when hemoptysis results in a life-threatening event, including significant airway obstruction, significant gas exchange alterations, or hemodynamic instability [54]. Criteria based solely on the volume of blood cannot be used precisely since quantifying the amount of blood that a patient has expectorated is challenging. Nonetheless, in our clinical practice, we also consider hemoptysis to be life-threatening when there has been approximately 150 mL of blood expectorated in a 24-hour period or bleeding at a rate ≥100 mL/hour [54]. For practical purposes, more than 150 mL is easily quantifiable by patients as roughly a half cup of blood in 24 hours.

Common etiologies — Any etiology associated with non-life-threatening hemoptysis (table 1) can also cause life-threatening hemoptysis, but a few etiologies account for most episodes of the latter.

While comprehensive epidemiologic data are lacking, common causes of life-threatening hemoptysis in developed countries include bronchiectasis (most often cystic fibrosis [CF]-related), tuberculosis (TB), airway neoplasms (primary and metastatic), and fungal infections (particularly aspergilloma) [58-60]. In a series of 58 patients undergoing arterial embolization for hemoptysis, underlying causes included CF-related bronchiectasis (40 percent), lung metastasis (14 percent), lung cancer (12 percent), and fungal infection (7 percent) [58]. In developing countries, TB remains the predominant cause [7,8,55,61-63]. However, there is significant geographic variation in the etiologic frequencies of life-threatening hemoptysis as shown in the table (table 2).

Bronchiectasis — In bronchiectasis, rapid bleeding and life-threatening hemoptysis can occur due to rupture of tortuous bronchial arteries or the submucosal capillary plexus, both of which are subjected to high pressure from the systemic circulation. The improved survival of patients with CF into adulthood has made CF-associated bronchiectasis an increasingly common cause of life-threatening hemoptysis in developed countries [64], although bronchiectasis from any cause may be associated with significant hemoptysis. (See "Clinical manifestations and diagnosis of bronchiectasis in adults", section on 'Etiologies'.)

Tuberculosis — Life-threatening hemoptysis can be due to either active or prior TB [55].

Active TB – Life-threatening hemoptysis due to active TB can occur in the setting of cavitary or noncavitary disease. The cause of the bleeding is usually due to bronchial arterial vessel ulceration [10]. Less often, active TB may cause sudden rupture of a Rasmussen aneurysm (ie, pseudoaneurysm) of the pulmonary artery [36]. There is some uncertainty about whether similar pseudoaneurysms can also arise from TB-infected bronchial arteries. (See "Pulmonary tuberculosis: Clinical manifestations and complications", section on 'Hemoptysis'.)

Prior TB – There are multiple causes of hemoptysis due to inactive prior TB. These include the erosion of a healed calcified lymph node (ie, broncholith) through a bronchial artery and into an airway, bronchiectasis due to structural lung damage from prior TB, a mycetoma in an old TB lung cavity, and scar carcinoma in areas of healed TB. Late rupture of a Rasmussen aneurysm also may occur in patients with prior TB [65].

Fungal infections — Fungal infections in the lung have increased in frequency, especially among patients with pre-existing cavitary disease and in immunocompromised patients (eg, hematopoietic cell transplantation).

Aspergilloma – Aspergilloma is a common cause of life-threatening hemoptysis. An aspergilloma is a fungus ball, also known as a mycetoma, composed of Aspergillus hyphae, fibrin, mucus, and cellular debris that is found within a pre-existing pulmonary cavity. The cavity may derive from various causes, such as chronic pulmonary sarcoidosis, emphysematous bullae, septic emboli, or hydatid cyst [26,66,67]. A mycetoma, can also be due to other fungal species. In many patients, aspergillomas (and mycetomas) are asymptomatic and non-progressive for prolonged periods of time. However, hemoptysis occurs in 50 to 90 percent of patients, at some point in their life [10,26,27]. Hemoptysis is generally non-life-threatening but in rare cases, can be life-threatening. The exact cause of bleeding due to an aspergilloma is uncertain. (See "Chronic pulmonary aspergillosis: Epidemiology, clinical manifestations and diagnosis".)

Invasive parenchymal fungal infections – Invasive parenchymal fungal infections may also cause hemoptysis, particularly infections caused by the angioinvasive fungi including Aspergillus (acute or chronic necrotizing aspergillosis) and Mucor [10,68]. The fungi destroy parenchymal and vascular structures, thereby inducing hemorrhage. There is increasing recognition of subacute progressive aspergillus infection in patients with chronic underlying lung disease, including severe chronic obstructive pulmonary disease (COPD). When invasive parenchymal fungal infection occurs after hematopoietic stem cell transplantation, bleeding may be more likely when bone marrow production of neutrophils returns (about day 100), since local inflammation may increase [69]. (See "Chronic pulmonary aspergillosis: Epidemiology, clinical manifestations and diagnosis" and "Epidemiology and clinical manifestations of invasive aspergillosis" and "Mucormycosis (zygomycosis)".)

Acute dimorphic fungal infections (eg, histoplasmosis, blastomycosis) rarely cause hemoptysis and, when they do, it is likely a consequence of mucosal erosion. Prior histoplasmosis has been reported as a potential cause of hemoptysis, either due to the erosion of a calcified lymph node through an airway and vessel, or the effects of fibrosing mediastinitis. (See "Pathogenesis and clinical features of pulmonary histoplasmosis" and "Clinical manifestations and diagnosis of blastomycosis", section on 'Pulmonary involvement'.)

Bronchogenic carcinoma — Bronchogenic cancer accounts for approximately 5 to 30 percent of cases of life-threatening hemoptysis, depending on the report [70-72]. In many cases, life-threatening bleeding may be heralded by smaller, sentinel bleeding events during the prior weeks [73]. Patients typically have large, centrally located tumors, especially squamous cell carcinoma. In a case series of 125 patients with life-threatening hemoptysis related to non-small cell lung cancer, bleeding was due to bronchial artery involvement in 82 percent, while bleeding due to involvement of the main pulmonary artery was rare (6 percent) [74]. Approximately half of these patients had squamous cell carcinoma.

Carcinoid tumors and endobronchial hemangiomas are highly vascular and are rare causes of life-threatening hemoptysis. (See "Lung neuroendocrine (carcinoid) tumors: Epidemiology, risk factors, classification, histology, diagnosis, and staging" and 'Bronchial neoplasm' above.)

Rare cancers such as papillary thyroid carcinoma causing tracheal invasion, malignant triton tumor (an aggressive peripheral nerve sheath tumor), and giant hamartoma have been reported to cause life-threatening hemoptysis [75-77].

Uncommon etiologies — There are several other causes of life-threatening hemoptysis that should be kept in mind in the absence of the more common causes listed above. These include:

Other lung infections – Other lung infections (particularly bacterial lung abscess and/or necrotizing pneumonia) can also cause life-threatening hemoptysis. Regardless of the type of lung infection, bleeding may occur acutely from necrosis of lung tissue or rupture of hypertrophied bronchial arteries due to inflammation.

Bacterial pneumonia (without necrosis) occasionally causes life-threatening hemoptysis, especially in individuals with a bleeding diathesis.

In developing countries, parasitic infections are common causes of life-threatening hemoptysis, particularly paragonimiasis in Southeast Asia.

Case reports of life-threatening hemoptysis have been described in patients with leptospirosis [78] and septic pulmonary emboli from right-sided infective endocarditis. (See "Overview of pulmonary disease in people who inject drugs", section on 'Septic emboli'.)

Immunologic lung diseases – Diffuse parenchymal lung diseases with an immunologic basis can cause life-threatening hemoptysis, probably due to pulmonary capillaritis. Examples include anti-glomerular basement membrane (anti-GBM; Goodpasture) disease, granulomatosis with polyangiitis, systemic lupus erythematosus (SLE), idiopathic pulmonary hemosiderosis, primary antiphospholipid antibody syndrome, Behçet syndrome, and microscopic polyangiitis [79]. Patients with these diseases may also present with diffuse alveolar hemorrhage (DAH) (table 3A-B). However, in DAH, the expectorated volume of hemoptysis may be relatively small compared with the amount of parenchymal bleeding. The reason for this observation is that the alveolar location of the bleeding may not stimulate the cough reflex to the same extent as bleeding in the airway. (See "The diffuse alveolar hemorrhage syndromes".)

Chemotherapy and bone marrow transplantation – Patients who are undergoing chemotherapy for leukemia or who have received a hematopoietic stem cell transplant (HSCT) rarely may have sudden, life-threatening pulmonary hemorrhage that is frequently fatal. In some cases this is due to DAH, an early complication of HSCT while in others, it is due to idiopathic pneumonia syndrome (IPS), which is a late complication of HSCT. Postmortem pathology suggests IPS is due to diffuse lung injury, presumably from a combination of drugs, radiation, and/or thrombocytopenia [80]. In cases of DAH or IPS, there may also be contributions from underlying fungal or viral infection. Idiopathic pneumonia syndrome is discussed separately. (See "Pulmonary complications after autologous hematopoietic cell transplantation" and "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes".)

Pulmonary vascular diseases – Cardiac and vascular etiologies are potential, albeit infrequent, causes of life-threatening hemoptysis in adults.

Pulmonary arteriovenous malformations (PAVMs) can bleed regardless of whether or not they are due to hereditary hemorrhagic telangiectasia (HHT; also called Osler-Weber-Rendu syndrome) or idiopathic [81,82]. In one series, more than 8 percent of patients with HHT-PAVMs had an episode of life-threatening hemoptysis [81]. An increased risk of life-threatening hemoptysis has been reported during pregnancy in patients with PAVMs. (See "Pulmonary arteriovenous malformations: Clinical features and diagnostic evaluation in adults" and "Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)", section on 'Pulmonary AVMs' and "Therapeutic approach to adult patients with pulmonary arteriovenous malformations", section on 'Pregnancy'.)

Mitral stenosis increases resistance in the pulmonary veins, accompanied by reversal of blood flow from the pulmonary capillaries into the bronchial veins. While hemoptysis is often minor, bronchial varix rupture may result in sudden, life-threatening bleeding ("pulmonary apoplexy"). This is prone to manifest at times of either increased pulmonary blood flow (exercise, pregnancy) or increased blood volume (pregnancy, hypervolemia). (See "Rheumatic mitral stenosis: Clinical manifestations and diagnosis", section on 'Hemoptysis'.)

Pulmonary embolism usually causes scant hemoptysis in association with peripheral pulmonary infarction. However, the hemoptysis may become life-threatening after the initiation of anticoagulant therapy or the use of a thrombolytic agent. (See "Epidemiology and pathogenesis of acute pulmonary embolism in adults", section on 'Clinical presentation, evaluation, and diagnosis'.)

Congenital heart disease or severe pulmonary hypertension can cause significant hemoptysis, especially in patients who undergo lung biopsy. (See "Hemoptysis in children", section on 'Pulmonary vascular disorders'.)

Acquired and iatrogenic trauma

Penetrating, rather than blunt, trauma may result in life-threatening hemoptysis (eg, gunshot wound). (See "Initial evaluation and management of penetrating thoracic trauma in adults".)

Right heart catheterization (ie, pulmonary artery catheterization) can result in pulmonary artery perforation and the sudden onset of life-threatening hemoptysis. Predispositions include pulmonary hypertension and having the catheter tip too distal in the pulmonary circulation, particularly for relatively long periods of time. The latter can also induce hemoptysis due to pulmonary infarction. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults", section on 'Complications'.)

Life-threatening hemoptysis may result from a variety of medical interventions, including percutaneous or transbronchial lung biopsy (<2 percent), cryobiopsy (<20 percent) [83,84], central vein venipuncture during pacemaker insertion [85], and ablative procedures for endobronchial masses. (See "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Bleeding' and "Bronchoscopic cryotechniques in adults", section on 'Complications' and "Endobronchial brachytherapy", section on 'Early' and "Endobronchial photodynamic therapy in the management of airway disease in adults", section on 'Photodynamic therapy specific'.)

Fistulas – Although an uncommon cause of hemoptysis, fistulas between the aorta and the airway (especially the left bronchopulmonary tree) are frequently associated with aneurysms of the thoracic aorta and are fatal if not diagnosed and surgically treated [86]. (See "Clinical manifestations and diagnosis of thoracic aortic aneurysm", section on 'Clinical presentations'.)

Tracheo-innominate fistulas are a rare but potentially life-threatening complication of tracheostomy, occurring most often if the tracheostomy tube is placed too low [87,88]. The tube can erode directly into the innominate artery, which crosses the anterolateral surface of the trachea at the level of the upper sternum. Bronchial stents are another source of fistula formation [89]. (See "Tracheostomy: Postoperative care, maintenance, and complications in adults", section on 'Late (≥7 to 10 days)'.)

Acute bronchitis – It is controversial whether acute bronchitis alone is sufficient to cause life-threatening hemoptysis and in our experience it is rare. Many clinicians believe that coagulopathy or other contributing factors must be present for life-threatening hemoptysis to occur in the setting of acute bronchitis alone. Older case series reported bronchitis as the cause of life-threatening hemoptysis in 5 to 37 percent of cases [1,7,8,90]. However, since computed tomography of the chest was rarely performed in these older series, it is possible that many of the patients actually had underlying bronchiectasis. In addition, many of the reported cases did not have follow-up, so it is unclear if other underlying causes remained undiagnosed. Life-threatening hemoptysis should be attributed to bronchitis only presumptively after careful and complete workup.

CRYPTOGENIC HEMOPTYSIS — Depending upon the study, up to 30 percent of patients with hemoptysis have no cause identified even after careful evaluation, including bronchoscopy and chest computed tomography. These patients are classified as having either cryptogenic or idiopathic hemoptysis [20,91,92].

Repeat investigation with recurrent events may eventually identify a cause. In a series that included 409 patients with cryptogenic hemoptysis, lung cancer developed in less than 2 percent over the ensuing five years [93]. A separate retrospective series stressed the finding of a superficial bronchial artery beneath the bronchial epithelium (Dieulafoy disease) in a subset of patients with cryptogenic hemoptysis who required surgery for massive hemoptysis [20]. In a series of 35 patients with cryptogenic hemoptysis, bronchial arteriography identified areas of hypervascularization or aneurysm in over 80 percent [94]. Similar findings were reported in a separate series of 22 patients [95].

PSEUDOHEMOPTYSIS — Blood from the upper respiratory tract and the upper gastrointestinal (GI) tract can be expectorated and, thus, mimic blood coming from the lower respiratory tract, a situation called pseudohemoptysis. In some occasions, upper airway and GI bleeding need to be simultaneously investigated with lower respiratory tract investigations before the true source can be confirmed. (See "Evaluation of nonlife-threatening hemoptysis in adults" and "Evaluation and management of life-threatening hemoptysis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hemoptysis".)

SUMMARY AND RECOMMENDATIONS

Definition -The term hemoptysis refers to expectoration of blood originating from the lower respiratory tract (ie, from below the vocal cords). There are several sources of bleeding within the lung and endobronchial tree that can be responsible for hemoptysis (table 1). (See 'Introduction' above.)

Circulation source - Most episodes of hemoptysis are non-life-threatening and originate from the pulmonary artery circulation. Although the bronchial artery circulation is responsible for only 2 percent of the total vascular supply to the lung, bleeding from a bronchial artery is the cause of life-threatening hemoptysis in 90 percent of cases. (See 'Bronchial versus pulmonary arterial origins of hemoptysis' above.)

Causes non-life-threatening - The most common causes of non-life-threatening hemoptysis in developed countries are acute bronchitis, bronchial neoplasms, and bronchiectasis, while infections due to Mycobacterium tuberculosis (TB) and Paragonimus westermani are more common causes in developing countries (table 1). (See 'Causes of non-life-threatening hemoptysis' above.)

Less common causes of non-life-threatening hemoptysis include other airway diseases (inhaled foreign body, vascular-airway fistulas, Dieulafoy lesions), parenchymal infections (eg, lung abscess, and aspergilloma), and immune disorders (eg, Goodpasture syndrome, systemic lupus erythematosus, granulomatosis with polyangiitis). (See 'Common etiologies' above.)

Rare etiologies include genetic disorders (eg, Ehlers-Danlos syndrome), endometriosis, pulmonary vascular disorders (eg, conditions that result in pulmonary venous and pulmonary arterial hypertension, pulmonary arterial venous malformations, aneurysms, embolism), trauma (including iatrogenic), bleeding disorders (eg, thrombocytopenia, coagulopathy), and several drugs or toxins (eg, cocaine, e-cigarette or vaping use). (See 'Miscellaneous' above.)

Causes life-threatening - We use the term “life-threatening hemoptysis” when hemoptysis results in life-threatening events, including significant airway obstruction, abnormal gas exchange, or hemodynamic instability. Hemoptysis is also considered life-threatening when there has been approximately 150 mL of blood expectorated in a 24-hour period or bleeding occurs at a rate ≥100 mL/hour. (See 'Definition' above.)

While any etiology associated with non-life-threatening hemoptysis can also be life-threatening, common causes of life-threatening hemoptysis include bronchiectasis, TB, bronchogenic carcinoma, and fungal infections (particularly aspergilloma) (table 1). (See 'Causes of life-threatening hemoptysis' above.)

Cryptogenic and pseudohemoptysis - Cryptogenic (or idiopathic) hemoptysis is a term given to cases where a cause of hemoptysis is not apparent after investigation, although evaluation during repeat episodes may reveal previously unidentified lesions (eg, Dieulafoy lesion, early carcinoma, arterial lesions). Pseudohemoptysis refers to expectorated blood that arises from the upper respiratory or upper gastrointestinal tract. (See 'Cryptogenic hemoptysis' above and 'Pseudohemoptysis' above.)

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References

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