Pulmonary Alveolar Haemorrhage

Pulmonary alveolar haemorrhage is a serious medical emergency where bleeding occurs within the tiny air sacs of the lungs, potentially causing severe breathing problems and requiring immediate medical attention.

Table of contents

• What is Pulmonary Alveolar Haemorrhage
• How It Happens in the Body
• What Causes This Condition
• Signs and Symptoms
• How Doctors Diagnose the Condition
• Treatment Options
• What to Expect

What is Pulmonary Alveolar Haemorrhage

Pulmonary alveolar haemorrhage, also called diffuse alveolar hemorrhage, is bleeding that occurs within the air sacs (alveoli) of the lungs^[1]. This is not a single disease, but rather a syndrome that can be caused by many different underlying conditions^[1].

The bleeding originates from the tiny blood vessels in the lungs, particularly the alveolar capillaries, which are the smallest blood vessels that surround the air sacs^[1]. When this happens, blood collects within the alveoli throughout the lung tissue, rather than being limited to just one area^[1].

This condition is considered a life-threatening medical emergency that requires immediate treatment^[3]. The condition can be persistent or recurrent, meaning it may happen once and continue, or it may come back multiple times^[1].

How It Happens in the Body

Pulmonary alveolar haemorrhage results from widespread damage to the small blood vessels in the lungs. This damage disrupts the alveolar-capillary basement membrane, which is the thin barrier between the air sacs and blood vessels, causing blood to leak into the alveoli^[1]. When enough alveoli fill with blood, the normal exchange of oxygen and carbon dioxide is disrupted, making it difficult to breathe^[1].

There are three main ways this damage can occur in the body^[1]:

• Pulmonary capillaritis: This involves inflammation where certain white blood cells (neutrophils) invade and destroy the walls of the tiny blood vessels in the lungs. This type most commonly occurs in diseases where the immune system attacks the body’s own tissues, such as ANCA-associated vasculitis and systemic lupus erythematosus^[1].
• Bland pulmonary hemorrhage: This refers to bleeding within the alveoli without significant inflammation. It typically occurs when people have blood clotting problems, take blood-thinning medications, or have heart problems that cause increased pressure on the left side of the heart, such as mitral stenosis^[1].
• Diffuse alveolar damage: This is the pattern seen in acute respiratory distress syndrome (ARDS), where bleeding occurs alongside widespread damage to the cells lining the alveoli and blood vessels, without inflammation of the blood vessel walls^[1].

These patterns can sometimes overlap, meaning a single underlying condition may show characteristics of more than one type^[1].

What Causes This Condition

Many different disorders can cause pulmonary alveolar haemorrhage. While autoimmune disorders are the most common cause, there are numerous other possibilities^[1].

The main causes include^[1][5]:

• Autoimmune disorders: Conditions where the immune system mistakenly attacks the body’s own tissues, including systemic vasculitides, anti-glomerular basement membrane disease, and antiphospholipid syndrome
• Heart disorders: Particularly mitral stenosis, where one of the heart valves becomes narrowed
• Blood clotting disorders: Problems with blood clotting caused by diseases or medications that prevent blood from clotting normally (anticoagulants)
• Medications and drugs: Certain drugs including propylthiouracil, amiodarone, methotrexate, nitrofurantoin, montelukast, infliximab, and crack cocaine^[1]
• Transplantation: Either bone marrow transplantation (hematopoietic stem cell transplantation) or solid organ transplantation
• Idiopathic pulmonary hemosiderosis: A rare disorder where the cause is unknown, possibly due to immune system problems^[5]
• Isolated pauci-immune pulmonary capillaritis: An immune disorder affecting people between ages 18 and 35 that damages tiny blood vessels in the lungs^[5]
• Lung infections: Including hantavirus infection and other viral infections
• Toxic exposures: Such as trimellitic anhydride, isocyanates, certain pesticides, and vaping^[1]

In some cases, the condition is associated with kidney problems (glomerulonephritis), and when this happens, it is called a pulmonary-renal syndrome^[1].

Signs and Symptoms

People with pulmonary alveolar haemorrhage typically develop symptoms suddenly^[1]. The most common symptoms include^[1][5]:

• Difficulty breathing (dyspnea)
• Cough
• Coughing up blood (hemoptysis)
• Fever

However, at least one-third of people with this condition do not cough up blood, even though there is bleeding in their lungs^[3]. When the condition is severe, breathing may become extremely difficult, and people may gasp for air and develop a bluish or pale grayish discoloration of the skin called cyanosis^[5].

Some people may also experience symptoms related to the underlying disease that caused the bleeding. For example, they might have a rash, joint pain, kidney problems, or eye problems^[1].

People who have repeated episodes of bleeding into the lungs can develop anemia (low blood count), which often causes fatigue. Over time, scarring of the lungs can occur, leading to pulmonary fibrosis^[5].

How Doctors Diagnose the Condition

Doctors can often diagnose pulmonary alveolar haemorrhage based on a person’s symptoms and imaging findings^[5]. However, because the condition can be caused by many different diseases, additional testing is usually needed to identify the underlying cause.

Imaging Tests

Chest imaging typically shows new areas of abnormal density (infiltrates) in the lungs^[1]. A chest x-ray or computed tomography (CT) scan may reveal patchy areas of opacity throughout the lungs, often with a pattern that spares the outer edges and the top portions of the lungs^[3].

Bronchoscopy

If the diagnosis is not clear from symptoms and imaging, doctors may need to perform a bronchoscopy, which involves inserting a flexible tube with a camera into the airways to look directly into the lungs^[5]. During this procedure, doctors can perform a bronchoalveolar lavage, where they wash out the lungs with fluid and then examine the fluid for blood^[3].

During bronchoscopy, doctors typically perform serial bronchoalveolar lavage, where three syringes of fluid are sequentially flushed into a bronchus and then collected^[8]. If the fluid becomes progressively bloodier with each wash, this suggests bleeding is coming from the alveoli rather than from the airways^[8].

The collected fluid can also be examined under a microscope to look for hemosiderin-laden macrophages, which are cells that have absorbed iron from broken-down red blood cells. Finding more than 20% of these cells supports the diagnosis, although they don’t appear until 24 to 72 hours after bleeding begins^[8].

Blood Tests

Blood tests are frequently performed to help identify the underlying cause^[1]. These may include tests for autoimmune markers, kidney function, blood counts, and blood clotting function. A falling hemoglobin level may provide a clue that bleeding is occurring, though this finding alone is not specific^[3].

Treatment Options

Treatment for pulmonary alveolar haemorrhage depends on the underlying cause. For people with autoimmune causes, treatment focuses on suppressing the immune system^[1][5].

Medications for Autoimmune Causes

For autoimmune conditions causing the bleeding, the main treatments include^[5][6]:

• Steroids (also called glucocorticoids or corticosteroids): These are given to reduce inflammation. High doses are typically used initially, often given through a vein
• Cyclophosphamide: A chemotherapy medication that suppresses the immune system
• Rituximab: Another type of immune suppression medication

In some cases, particularly when antibodies are causing the problem, doctors may use plasmapheresis, a procedure that filters antibodies out of the blood^[6].

Supportive Care

All patients need supportive care, which may include^[1][6]:

• Supplemental oxygen to help with breathing
• Correction of blood clotting problems
• Stopping medications that may be contributing to bleeding
• Support for blood pressure and heart function
• In severe cases, mechanical ventilation (breathing machine) may be needed

Experimental Treatments

In critical cases where standard treatments are not working, doctors may consider using activated recombinant factor VII (FVIIa), a medication that helps blood clot. This can be given either through the bloodstream or directly into the lungs^[6]. However, there are no large studies proving its effectiveness and safety, so its use remains controversial^[6].

What to Expect

The outlook for people with pulmonary alveolar haemorrhage varies significantly depending on the underlying cause and how quickly treatment is started^[3]. Early recognition and prompt treatment are crucial for survival^[3].

The condition has a high mortality rate, and some people may die from the bleeding or from complications related to difficulty breathing^[5]. The two-year survival rate can range from 20% to 90%, depending on what caused the bleeding^[9].

People who survive repeated episodes of bleeding may develop long-term complications, including^[5][9]:

• Anemia (low blood count)
• Organizing pneumonia
• Pulmonary fibrosis (lung scarring)
• Side effects from medications used for treatment

Despite the severity of this condition, with proper diagnosis and aggressive treatment, particularly of autoimmune causes, many people can recover and avoid future episodes.