OVERVIEW

What is Diffuse Alveolar Hemorrhage?

Diffuse alveolar hemorrhage is not an independent disease but rather a severe complication of various underlying conditions.

It is caused by pulmonary vascular damage (including capillaries, arterioles, and venules) due to multiple diseases, leading to red blood cell accumulation in the alveoli and triggering related symptoms. Patients often present with hemoptysis, accompanied by anemia and hypoxia-related manifestations.

Is Diffuse Alveolar Hemorrhage Serious?

Diffuse alveolar hemorrhage can occur at any age, including infants and children. The condition may progress slowly or emerge abruptly, often becoming life-threatening.

It can manifest chronically and insidiously or acutely and explosively, rapidly progressing to respiratory failure, requiring mechanical ventilation with advanced respiratory support.

Who Is Prone to Diffuse Alveolar Hemorrhage?

Clinically, most patients with diffuse alveolar hemorrhage experience sudden onset and complex etiology. It typically occurs in individuals with underlying conditions such as infections, poisoning, drug reactions, chemical exposure, autoimmune diseases, systemic vasculitis, hematologic disorders, or hematopoietic stem cell transplantation.

The acute-phase mortality rate is 64.3% for vasculitis-associated diffuse alveolar hemorrhage and 76.2% for hematologic system-related cases.

Therefore, suspected cases should be promptly diagnosed, with aggressive identification of the cause and immediate effective treatment.

SYMPTOMS

What impact does diffuse alveolar hemorrhage have on the human respiratory system?

The main manifestations of diffuse alveolar hemorrhage include nonspecific respiratory symptoms such as fever, hemoptysis, cough, sputum production, and shortness of breath.

Hemoptysis is the most characteristic manifestation of this condition. The degree of hemoptysis varies among most patients with diffuse alveolar hemorrhage—some may only cough up blood-streaked sputum, while others experience massive hemoptysis, leading to shock.

A small number of patients show no visible hemoptysis despite widespread alveolar hemorrhage. The amount of blood coughed up varies significantly among individuals, with some patients exhibiting severe anemia despite minimal hemoptysis.

One of the main manifestations of diffuse alveolar hemorrhage is hemoptysis, so how can one distinguish between hemoptysis and hematemesis?

When a patient presents with "coughing or vomiting blood," it is essential to differentiate between hemoptysis and hematemesis:

• Hemoptysis is usually preceded by symptoms such as throat irritation, chest tightness, or coughing, accompanied by cyanosis in the limbs and face. The vomited material is often bright red, mixed with foam and sputum.

• Hematemesis, on the other hand, is often accompanied by abdominal discomfort, nausea, and vomiting. The vomited material tends to be dark red and may contain food residues.

How does diffuse alveolar hemorrhage affect other systems in the human body?

• Urinary system: Hematuria is the most common symptom, but patients may also experience lower back pain, proteinuria, or dysuria.

• Digestive system: Symptoms such as abdominal pain, bloating, vomiting, nausea, melena, and jaundice may occur.

• Nervous system: Patients often experience seizures, limb numbness, and other neurological symptoms.

• Hematologic system: Skin manifestations such as petechiae, ecchymoses, and purpura may appear.

CAUSES

What are the pathogenic factors of diffuse alveolar hemorrhage?

The pathogenesis of diffuse alveolar hemorrhage remains unclear, and such cases are relatively rare in clinical practice. The underlying diseases that may lead to diffuse alveolar hemorrhage include the following:

• Pulmonary small vessel vasculitis-related: Mainly includes anti-neutrophil cytoplasmic antibody-associated vasculitis and immune complex-mediated small vessel vasculitis.

• Connective tissue disease-related: Includes systemic lupus erythematosus, Behçet's disease, mixed connective tissue disease, etc.

• Infection-related: Various viral and microbial infections, including cytomegalovirus, influenza virus, human immunodeficiency virus, herpes simplex virus, varicella-zoster virus, hepatitis B virus, hepatitis C virus, Pneumocystis jirovecii, Aspergillus, Leptospira, etc.

• Drug and toxin-related: Includes cocaine, penicillamine, amiodarone, amphotericin B, nitrofurantoin, propylthiouracil, retinoic acid, hydralazine, anticoagulants (such as warfarin, tirofiban, low molecular weight heparin), etc.

• Other causes: Such as coagulation disorders, disseminated intravascular coagulation, mitral stenosis, pulmonary radiation therapy, etc.

DIAGNOSIS

How to Diagnose Diffuse Alveolar Hemorrhage?

Most cases of diffuse alveolar hemorrhage are severe and progress rapidly, constituting a clinical emergency. Therefore, early fiberoptic bronchoscopy (FOB), prompt diagnosis, and targeted treatment are key to reducing mortality.

First, it is essential to determine whether the patient has a history of underlying conditions (e.g., heart disease, diabetes, digestive system disorders), medication use, or exposure history—particularly pulmonary vasculitis, connective tissue diseases, hematopoietic stem cell transplantation, or exposure to specific drugs, toxins, or radiation.

Patients presenting with cough, hemoptysis, dyspnea, and a hemoglobin drop of ≥20 g/L within 24 hours should be evaluated for possible diffuse alveolar hemorrhage.

What Tests Are Needed for Diagnosing Diffuse Alveolar Hemorrhage?

• For suspected diffuse alveolar hemorrhage, chest X-ray and high-resolution chest CT should be performed promptly. Chest CT typically reveals bilateral diffuse ground-glass opacities and interstitial lung lesions. As the condition improves, these shadows gradually resolve within weeks.

• Pulmonary function tests are also critical, often showing increased diffusing capacity and hypoxemia with possible hyperventilation.

• In emergencies, bronchoalveolar lavage (BAL) is required. Findings include bloody fluid from multiple lung segments and increased hemosiderin-laden macrophages after 48 hours. BAL confirms the diagnosis, aids in blood clearance, and improves gas exchange.

What Diseases Should Be Differentiated from Diffuse Alveolar Hemorrhage?

• Common causes of hemoptysis, such as bronchiectasis, pneumonia, tuberculosis, or lung tumors. These typically present with clear evidence of infection, absence of rapidly progressing anemia, and localized rather than diffuse lung shadows on CT.

• Pulmonary thromboembolism may cause dyspnea, minor hemoptysis, and lung shadows, but these shadows are non-diffuse, without marked dyspnea or progressive anemia. A history of deep vein thrombosis or prolonged immobility is often present.

• Cardiogenic pulmonary edema (e.g., acute left heart failure, mitral stenosis) may lead to pink frothy sputum and elevated B-type natriuretic peptide (BNP).

TREATMENT

How should diffuse alveolar hemorrhage be treated after confirmation?

After confirming the diagnosis of diffuse alveolar hemorrhage, the primary focus should be on actively treating the underlying disease and eliminating contributing factors. For alveolar hemorrhage caused by infection, infection control should be prioritized.

For patients diagnosed with autoimmune alveolar hemorrhage, immunosuppressants and corticosteroids are the main treatments. In severe cases, high-dose steroid pulse therapy should be administered. High-dose methylprednisolone (500–2,000 mg/day) can improve the prognosis of patients with diffuse alveolar hemorrhage, with gradual tapering as the condition improves.

If glucocorticoid pulse therapy alone is ineffective, cyclophosphamide pulse therapy can be added: 750–1,000 mg/m², administered intravenously every 3–4 weeks. Once the condition stabilizes, the dose can be reduced to a maintenance level of 1–2 mg/(kg·day), which may be combined with a maintenance dose of prednisone.

Other immunosuppressants, such as azathioprine, cyclosporine, mycophenolate mofetil, and methotrexate, may also be considered.

Intravenous high-dose immunoglobulin can be combined to control diffuse alveolar hemorrhage and has some efficacy as adjunctive anti-infection therapy.

Plasmapheresis or immunoadsorption helps remove plasma antibodies and protect renal function, serving as an auxiliary treatment for diffuse alveolar hemorrhage.

What are the emergency measures for massive hemoptysis in diffuse alveolar hemorrhage?

Massive hemoptysis is defined as coughing up more than 100 mL of blood in a single episode or over 500 mL within 24 hours. If diffuse alveolar hemorrhage is suspected, the patient should be immediately hospitalized and treated with hemostatic drugs such as vitamin K, adrenochrome, etamsylate, and pituitrin.

Simultaneously, fluid replacement and blood transfusion should be administered, with interventional surgery considered if necessary. If the patient experiences sudden chest tightness, difficulty breathing, ineffective hemoptysis, cyanosis, profuse sweating, or gasping during hemoptysis, asphyxia should be suspected.

The patient should be immediately placed in a prone position with the head lower than the feet, and back patting should be performed to facilitate blood expulsion while arranging urgent medical transfer.

Is diffuse alveolar hemorrhage prone to recurrence?

With the increasing misuse and expanded indications of medications, drug-induced diffuse alveolar hemorrhage warrants sufficient attention. If the causative drugs—such as anticoagulants, thrombolytics, or chemotherapy agents—are discontinued, recurrence is generally unlikely.

Additionally, controlling viral, bacterial, or fungal infections reduces the likelihood of recurrence. However, if the patient has underlying conditions like systemic lupus erythematosus, microscopic polyangiitis, or Goodpasture syndrome, diffuse alveolar hemorrhage is more likely to recur.

Can diffuse alveolar hemorrhage be cured?

Not necessarily.

For non-immune causes, correcting the underlying condition usually improves the hemorrhage. If the condition is triggered by medications (e.g., anticoagulants, thrombolytics, or chemotherapy) or infections (viral, bacterial, or fungal), discontinuing the drugs and treating the infection often leads to a cure.

For patients with immune-related underlying diseases, diffuse alveolar hemorrhage may be cured if the primary condition is treated, though the disease may cause lasting lung damage.

DIET & LIFESTYLE

What should be noted after recovery from diffuse alveolar hemorrhage?

Recurrent diffuse alveolar hemorrhage can lead to irreversible interstitial fibrosis, with short-term and long-term survival rates varying depending on the underlying cause. After clinical cure, during recovery, it is necessary to adjust corresponding lifestyle and dietary patterns based on the underlying cause.

PREVENTION

How to prevent diffuse alveolar hemorrhage?

Since the etiology and pathogenesis of diffuse alveolar hemorrhage remain unclear, there is no specific prevention method.

As the condition of most patients progresses rapidly, often accompanied by progressive deterioration of renal function, the timing of treating the underlying disease significantly impacts prognosis.

Early treatment of the underlying disease can improve remission and cure rates. If diffuse alveolar hemorrhage is highly suspected, seek medical attention immediately.