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Diffuse Alveolar Hemorrhage

By

Joyce Lee

, MD, MAS, University of Colorado School of Medicine

Last full review/revision Sep 2021| Content last modified Sep 2021
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Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage. 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 tests are 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 pulmonary small 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 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; however, many patients present with acute respiratory failure Acute Hypoxemic Respiratory Failure (AHRF, ARDS) Acute hypoxemic respiratory failure is severe arterial hypoxemia that is refractory to supplemental oxygen. It is caused by intrapulmonary shunting of blood resulting from airspace filling or... read more Acute Hypoxemic Respiratory Failure (AHRF, ARDS) , sometimes leading to death. 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.

Pearls & Pitfalls

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

There are no specific physical examination findings.

Other manifestations depend on the underlying disorder (eg, diastolic murmur in patients with mitral stenosis).

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 is used for virtually all diagnostic, and most therapeutic, indications. Flexible bronchoscopes... 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)

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.

Serologic Tests for Disorders Causing Diffuse Alveolar Hemorrhage

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 diagnosis.

Echocardiography Echocardiography This photo shows a patient having echocardiography. This image shows all 4 cardiac chambers and the tricupsid and mitral valves. Echocardiography uses ultrasound waves to produce an image of... read more Echocardiography may be indicated to exclude mitral stenosis. Lung biopsy or, if the urinalysis is abnormal, kidney biopsy is frequently needed when a cause remains unclear or the progression of disease is too rapid to await the results of serologic testing.

Prognosis of Diffuse Alveolar Hemorrhage

Patients can require mechanical ventilation Overview of Mechanical Ventilation Mechanical ventilation can be Noninvasive, involving various types of face masks Invasive, involving endotracheal intubation Selection and use of appropriate techniques require an understanding... read more and even die as a result of hemorrhage-associated respiratory failure. Recurrent alveolar hemorrhage causes pulmonary hemosiderosis and fibrosis, both of which develop when ferritin aggregates within alveoli and exerts toxic effects. COPD Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more Chronic Obstructive Pulmonary Disease (COPD) (chronic obstructive pulmonary disease) occurs in some patients with recurrent diffuse alveolar hemorrhage secondary to microscopic polyarteritis.

Treatment of Diffuse Alveolar Hemorrhage

  • Corticosteroids

  • Sometimes cyclophosphamide, rituximab, or plasma exchange

  • Supportive measures

Treatment involves correcting the cause.

Corticosteroids and possibly cyclophosphamide are used to treat vasculitides, connective tissue disorders, and Goodpasture syndrome Treatment Goodpasture syndrome, a subtype of pulmonary-renal syndrome, is an autoimmune syndrome consisting of alveolar hemorrhage and glomerulonephritis caused by circulating anti-glomerular basement... read more Treatment . Rituximab has been studied primarily in ANCA-associated vasculitis and has been shown to be noninferior to cyclophosphamide for induction treatment (1 Treatment references Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage. There are numerous causes, but autoimmune disorders are most common. Most patients present with dyspnea, cough, hemoptysis... read more Treatment references ) and superior to azathioprine for remission treatment (2 Treatment references Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage. There are numerous causes, but autoimmune disorders are most common. Most patients present with dyspnea, cough, hemoptysis... read more Treatment references ). Rituximab has also been used to treat alveolar hemorrhage related to systemic lupus erythematosus, Goodpasture syndrome, and antiphospholipid antibody syndrome.

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

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, and/or immunosuppressants for autoimmune causes).

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