Introduction
Diffuse alveolar hemorrhage (DAH) is a condition characterized by persistent or recurrent pulmonary bleeding (bleeding in the lower respiratory tract). It is a life-threatening disorder caused by several conditions associated with anemia, hemoptysis (coughing up blood), diffuse lung infiltration, and acute respiratory failure. DAH is not a specific condition but a syndrome that is associated with a specific differential diagnosis and a sequence of testing.
What Is Diffuse Alveolar Hemorrhage?
Diffuse alveolar hemorrhage is a life-threatening disorder characterized by recurrent or persistent pulmonary hemorrhage (bleeding). However, it is different from pulmonary hemorrhage. Pulmonary hemorrhage denotes the extravasation of blood into the alveolar spaces, which denotes bleeding into the lower respiratory tract. Diffuse alveolar hemorrhage is characterized by a sudden and widespread infiltration of blood into the alveolar spaces, which is not limited to a section of the lungs.
How Does Diffuse Alveolar Hemorrhage Occur?
Diffuse alveolar hemorrhage is caused by widespread damage to the small vessels of the pulmonary vasculature, such as alveolar capillaries, arterioles, and venules, resulting in the collection of blood within the alveoli (tiny sac-like structures that allow gaseous exchange) of the lungs. This infiltration of blood into the alveolar spaces affects the gaseous exchange. Diffuse alveolar hemorrhage usually causes diffuse bleeding but may be focal in some cases.
What Causes Diffuse Alveolar Hemorrhage?
Diffuse alveolar hemorrhage can be caused by a variety of conditions. Any injury to the alveolar microvasculature can result in alveolar hemorrhage. Diffuse alveolar hemorrhage usually occurs in three patterns that reflect the nature of the underlying injury. DAH includes the following causes:
DAH Associated With Pathologic Capillaritis:
Primary Idiopathic Small Vessel Vasculitis:
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Wegener’s granulomatosis (inflammation of the blood vessels).
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Churg-Strauss syndrome (inflammation of blood vessels).
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Microscopic polyangiitis (inflammation of small blood vessels).
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Isolated pauci-immune glomerulonephritis (inflammation of blood vessels with rapidly progressing renal failure).
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Idiopathic pauci-immune glomerulonephritis (same as isolated type, but it arises spontaneously).
Primary Immune-Complex-Mediated Vasculitis:
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Goodpasteur’s syndrome (an autoimmune disorder in which the lungs and kidneys are affected).
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Henoch-Schnolein purpura (inflammation and bleeding in the small vessels of the joints, skin, intestines, and kidneys).
Secondary Vasculitis:
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Classic autoimmune disease (a condition in which the body’s immune system attacks its own cells).
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Systemic lupus erythematosus (an autoimmune disease affecting the skin, joints, kidneys, blood cells, brain, heart, and lungs).
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Rheumatoid arthritis (an autoimmune disorder in which the joints are affected).
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Antiphospholipid antibody syndrome (an autoimmune disorder that affects the normal proteins in the blood).
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Mixed connective tissue disease (a rare autoimmune disorder in which a specific antibody is present).
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Polymyositis (inflammation and weakness of the muscles) or dermatomyositis (an inflammatory disease with muscle weakness and skin rashes).
DAH Without Pathologic Capillaritis (Bland Pulmonary Hemorrhage):
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Idiopathic pulmonary hemosiderosis (a disorder with repeated episodes of DAH, leading to permanent lung damage).
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Coagulopathy is associated with anticoagulants, anti-platelets, Disseminated intravascular coagulation, and thrombolytics.
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Mitral stenosis (valvular heart disease).
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Pulmonary venous-occlusive disease (obstruction of small pulmonary veins resulting in right heart failure).
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Toxin or inhalation injury due to crack cocaine, isocyanates, and retinoic acid.
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Goodpasteur’s syndrome.
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Systemic lupus erythematosus.
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Drug-associated diseases due to Amiodarone, Penicillamine, and Nitrofurantoin.
DAH and Other Conditions:
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Bone marrow transplantation.
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Cytotoxic drug therapy.
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Radiation therapy.
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Acute respiratory distress syndrome (shortness of breath due to collection of fluid in the alveoli of the lungs).
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Other conditions like infection, embolism, or malignancy.
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Essential cryoglobulinemia (a condition in which blood proteins clump together to cause organ damage).
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Behcet’s disease (inflammation of blood vessels).
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Acute lung transplantation rejection.
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Drug-induced DAH.
DAH Associated With Vasculitis or Capillaritis:
Most of the cases of diffuse alveolar hemorrhage are caused by pulmonary capillaritis. Also, DAH is associated with systemic vasculitis, systemic lupus erythematosus, and collagen vascular diseases. It is also related to several other conditions, including transplantation and the use of certain drugs.
Bland Pulmonary Hemorrhage (DAH Without Capillaritis or Vasculitis):
In this condition, infiltration of the red blood cells (RBCs) into the alveolar spaces is seen without the presence of inflammation or destruction of the alveolar microvasculature. It has been found that anti-GBM (glomerular basement membrane) disease and systemic lupus erythematosus can induce both bland pulmonary hemorrhage and pulmonary capillaritis.
DAH Associated With Other Conditions:
In this type, diffuse alveolar hemorrhage is caused by conditions other than pulmonary vasculitis or the direct extravasation of red blood cells, such as inhalation or cytotoxic drug therapy.
What Are the Signs and Symptoms of Diffuse Alveolar Hemorrhage?
Mild forms of diffuse alveolar hemorrhage present with symptoms such as cough, dyspnea (shortness of breath), and fever. In addition, most patients present with acute respiratory failure, which may sometimes become fatal. Hemoptysis (coughing up blood) is a common symptom of DAH but may not be present in one-third of the patients. Most patients experience anemia and bleeding, resulting in reduced hematocrit (the percentage by volume of red blood cells in the blood). There are no specific clinical findings of DAH. Other signs and symptoms depend on the underlying condition (for example, a diastolic murmur in patients with mitral stenosis).
What Are the Complications of DAH?
Recurrent diffuse alveolar hemorrhage can result in organizing pneumonia, collagen deposition, and eventually pulmonary fibrosis.
How Is DAH Diagnosed?
The diagnosis depends on the history, clinical examination, radiographic imaging, bronchoscopy, and laboratory studies. The presence of dyspnea, cough, and hemoptysis with radiographic findings suggest the presence of DAH. A chest X-ray shows diffuse bilateral alveolar infiltration. A bronchoscopy with bronchoalveolar lavage is performed to confirm the diagnosis. The specimens obtained show the presence of numerous RBCs. In addition, the lavage fluid used remains hemorrhagic. Other laboratory tests, such as complete blood count, coagulation studies, platelet count, and serological tests, are also performed. Pulmonary function tests may be done to monitor the lung function.
How Is DAH Treated?
Treatment for DAH depends on the underlying cause. Corticosteroids are used for treating vasculitis, connective disorders, and Goodpasteur’s syndrome. Plasma exchange (a machine is used to separate the plasma from the blood cells, and the blood cells are mixed with a liquid and returned to the body to replace the plasma) is also used in the treatment of Goodpasteur’s syndrome. Recombinant-activated human factor VII is also used to treat severe DAH. Other measures include the use of supplemental oxygen, reversal of coagulopathy, the use of bronchodilators, and protective intubation for acute respiratory distress syndrome and mechanical ventilation.
Conclusion:
Diffuse alveolar hemorrhage is a condition caused by various disorders. Careful examination, medical history, and laboratory studies help in diagnosing this condition. Early diagnosis, a systematic approach, and aggressive treatment help decrease the mortality and morbidity associated with diffuse alveolar hemorrhage.
