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Diffuse Alveolar Hemorrhage

By

Joyce Lee

, MD, MAS, University of Colorado School of Medicine

Reviewed/Revised Oct 2023
View PATIENT EDUCATION
Topic Resources

Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage that originates from the lung parenchyma (ie, the alveoli) as opposed to the airways. There are numerous causes, but autoimmune disorders are most common. Most patients present with dyspnea, cough, hemoptysis, and new alveolar infiltrates on chest imaging. Diagnostic testing is directed at the suspected cause. Treatment is with immunosuppressants for patients with autoimmune causes and respiratory support if needed.

Pathophysiology of Diffuse Alveolar Hemorrhage

Diffuse alveolar hemorrhage results from widespread damage to the small pulmonary vessels, leading to blood collecting within the alveoli. If enough alveoli are affected, gas exchange is disrupted. The specific pathophysiology and manifestations vary depending on cause. For example, isolated pauci-immune pulmonary capillaritis is a small-vessel vasculitis Overview of Vasculitis Vasculitis is inflammation of blood vessels, often with ischemia, necrosis, and organ inflammation. Vasculitis can affect any blood vessel—arteries, arterioles, veins, venules, or capillaries... read more Overview of Vasculitis limited to the lungs; its only manifestation is alveolar hemorrhage typically affecting people aged 18 to 35 years.

Etiology of Diffuse Alveolar Hemorrhage

Many disorders can cause alveolar hemorrhage; they include

Symptoms and Signs of Diffuse Alveolar Hemorrhage

Symptoms and signs of milder diffuse alveolar hemorrhage are dyspnea, cough, and fever. Hemoptysis is common but may be absent in up to one third of patients. Most patients have anemia and ongoing bleeding, leading to a reduced hematocrit. Many patients present with acute respiratory failure Acute Hypoxemic Respiratory Failure (AHRF, ARDS) Acute hypoxemic respiratory failure is defined as severe hypoxemia (PaO2 (See also Overview of Mechanical Ventilation.) Airspace filling in acute hypoxemic respiratory failure (AHRF) may result... read more Acute Hypoxemic Respiratory Failure (AHRF, ARDS) , sometimes leading to death.

Pearls & Pitfalls

  • Hemoptysis may be absent in up to one third of patients with diffuse alveolar hemorrhage.

There are no specific physical examination findings.

Diagnosis of Diffuse Alveolar Hemorrhage

  • Chest x-ray

  • Bronchoalveolar lavage

  • Serologic and other tests to diagnose the cause

Diagnosis is suggested by dyspnea, cough, and hemoptysis accompanied by chest x-ray findings of diffuse bilateral alveolar infiltrates and a suspicion of diffuse alveolar hemorrhage.

Bronchoscopy Bronchoscopy Bronchoscopy is the introduction of an endoscope into the airways. Flexible fiberoptic bronchoscopy (rather than rigid bronchoscopy) is used for virtually all diagnostic, and most therapeutic... read more Bronchoscopy with bronchoalveolar lavage (BAL) is strongly recommended to confirm the diagnosis, particularly when manifestations are atypical or an airway source of hemorrhage has not been excluded. Specimens show blood with numerous erythrocytes and siderophages; lavage fluid typically remains hemorrhagic or becomes increasingly hemorrhagic after sequential sampling.

Evaluation of the cause

Other routine tests include

  • Complete blood count (CBC)

  • Coagulation studies

  • Platelet count

  • Serologic tests (antinuclear antibody, anti–double-stranded DNA [anti-dsDNA], antiglomerular basement membrane [anti-GBM] antibodies, antineutrophil cytoplasmic antibodies [ANCA], antiphospholipid antibody, complement levels)

Serologic tests are done to look for underlying disorders. Perinuclear-ANCA (p-ANCA) titers are elevated in some cases of isolated pauci-immune pulmonary capillaritis.

Other tests depend on clinical context. When patients are stable, pulmonary function tests Overview of Tests of Pulmonary Function Pulmonary function tests provide measures of airflow, lung volumes, gas exchange, response to bronchodilators, and respiratory muscle function. Basic pulmonary function tests available in the... read more may be done to document lung function. They may show increased diffusing capacity for carbon monoxide (DLCO) due to increased uptake of carbon monoxide by intra-alveolar hemoglobin; however, this finding, which is consistent with hemorrhage, does not assist with establishing a specific diagnosis.

Lung biopsy or, if the urinalysis is abnormal, kidney biopsy may be needed when a cause remains unclear or the progression of disease is too rapid to await the results of serologic testing.

Treatment of Diffuse Alveolar Hemorrhage

  • Corticosteroids

  • Sometimes cyclophosphamide, rituximab, or plasma exchange

  • Supportive measures

Corticosteroids and possibly cyclophosphamide are used to treat vasculitides Overview of Vasculitis Vasculitis is inflammation of blood vessels, often with ischemia, necrosis, and organ inflammation. Vasculitis can affect any blood vessel—arteries, arterioles, veins, venules, or capillaries... read more Overview of Vasculitis , systemic rheumatic disorders, and Goodpasture syndrome Treatment Goodpasture syndrome, a type of pulmonary-renal syndrome, is an autoimmune syndrome consisting of alveolar hemorrhage and glomerulonephritis caused by circulating anti-glomerular basement membrane... read more Treatment . Rituximab has been studied primarily in ANCA-associated vasculitis and has been shown to be noninferior to cyclophosphamide for induction treatment (2 Treatment references Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage that originates from the lung parenchyma (ie, the alveoli) as opposed to the airways. There are numerous causes, but... read more Treatment references ) and superior to azathioprine for remission treatment (3 Treatment references Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage that originates from the lung parenchyma (ie, the alveoli) as opposed to the airways. There are numerous causes, but... read more Treatment references ). Rituximab has also been used to treat alveolar hemorrhage related to systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more Systemic Lupus Erythematosus (SLE) , Goodpasture syndrome, and antiphospholipid syndrome Antiphospholipid Syndrome (APS) Antiphospholipid syndrome is an autoimmune disorder characterized by venous and arterial thrombosis or pregnancy complications (eg, recurrent miscarriage) and persistent autoantibodies to phospholipid-bound... read more .

Several studies have reported successful use of recombinant activated human factor VII in treating severe unresponsive alveolar hemorrhage, but such therapy is controversial because of possible thrombotic complications.

Treatment references

  • 1. Chung SA, Langford CA, Maz M, et al: 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol 73(8):1366–1383, 2021. doi:10.1002/art.41773

  • 2. Specks U, Merkel PA, Seo P, et al: Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med 369:417–427, 2013. doi: 10.1056/NEJMoa1213277

  • 3. Guillevin L, Pagnoux C, Karras A, et al: Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. New Engl J Med 371:1771–1780. 2014. doi: 10.1056/NEJMoa1404231

Prognosis for Diffuse Alveolar Hemorrhage

Key Points

  • Although diffuse alveolar hemorrhage can have various causes (eg, infection, toxins, drugs, hematologic or cardiac disorders), autoimmune disorders are the most common causes.

  • Symptoms, signs, and chest-x-ray findings are not specific.

  • Confirm diffuse alveolar hemorrhage by doing bronchoalveolar lavage to show persistent hemorrhage with sequential lavage samples.

  • Test for the cause by doing routine laboratory tests, autoantibody testing, and sometimes other tests.

  • Treat the cause (eg, with corticosteroids, cyclophosphamide, rituximab, plasma exchange).

Drugs Mentioned In This Article

Drug Name Select Trade
No brand name available
Cordarone, Nexterone, Pacerone
Jylamvo, Otrexup, Rasuvo, RediTrex, Rheumatrex, Trexall, Xatmep
Furadantin, Macrobid, Macrodantin, Urotoin
Singulair
AVSOLA, INFLECTRA, Remicade, RENFLEXIS, Zymfentra
Cyclophosphamide, Cytoxan, Neosar
RIABNI, Rituxan, RUXIENCE, truxima
Azasan, Imuran
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