What is the management of diffuse alveolar hemorrhage?

Management of Diffuse Alveolar Hemorrhage

For patients with diffuse alveolar hemorrhage (DAH) with hypoxemia, aggressive treatment with a combination of glucocorticoids plus either cyclophosphamide or rituximab is the standard of care, with plasma exchange considered as an additional therapy due to the high mortality risk. 1

Diagnosis and Initial Assessment

• DAH is characterized by the accumulation of red blood cells in the alveolar spaces, originating from pulmonary capillaries or venules 2
• Clinical presentation includes acute-onset cough, hemoptysis (may be absent initially), diffuse pulmonary infiltrates on imaging, anemia, and hypoxemic respiratory failure 3
• Diagnosis is established through:
  • Clinical features and radiological patterns 2
  • Bronchoalveolar lavage (BAL) showing increasingly bloody returns in sequential aliquots 1
  • Chest imaging showing bilateral pulmonary infiltrates 4
• DAH with hypoxemia has a high early mortality risk and requires prompt intervention 1

Etiology Assessment

• Determine whether DAH is immune-mediated or non-immune-mediated 2:
  • Immune causes: vasculitides (especially ANCA-associated vasculitis), connective tissue diseases (especially systemic lupus erythematosus), and anti-glomerular basement membrane disease 2
  • Non-immune causes: heart diseases, coagulation disorders, infections, drug toxicities, post-hematopoietic cell transplantation 2, 5
• In ANCA-associated vasculitis (AAV), DAH occurs in approximately 25% of patients 1
• Risk factors for mortality in AAV-associated DAH include older age, severe kidney failure, degree of hypoxemia, and involvement of >50% of lung area 1

Treatment Algorithm

1. Initial Management (Immediate)

• Ensure airway protection and adequate oxygenation 1
• For clinically unstable patients with massive hemoptysis, bronchoscopy may be needed to clear airways of blood clots and potentially tamponade the bleeding site 1
• Assess extent of lung involvement with chest radiography (two or more opacified lung quadrants correlate with increased mortality risk) 1

2. Specific Therapy for Immune-Mediated DAH

• First-line therapy:

  • High-dose glucocorticoids (intravenous) plus either cyclophosphamide or rituximab 1
  • For patients in intensive care or on mechanical ventilation, minimize glucocorticoid use and avoid leukopenia due to high infection risk 1

• Additional therapies to consider:

  • Plasma exchange should be considered for DAH with hypoxemia, despite the PEXIVAS trial not showing clear benefit in the primary composite outcome 1
  • The American Society of Apheresis recommends plasma exchange for severe DAH 1
  • High-dose intravenous immunoglobulins may be considered, particularly in intensive care settings 1

3. Management of Refractory Disease

• For refractory disease, consider:
  • Increasing glucocorticoid dose (intravenous or oral) 1
  • Switching from cyclophosphamide to rituximab or vice versa 1
  • Adding plasma exchange if not already implemented 1
  • Intravenous immunoglobulin therapy may neutralize ANCA and serve as an adjunct therapy 1

4. Non-Immune DAH Management

• Treatment should target the underlying cause 2
• For post-hematopoietic cell transplantation DAH:
  • Supportive care, systemic corticosteroids, platelet transfusions 5
  • Consider antifibrinolytic drugs and topical procoagulant factors 5

Special Considerations

• DAH without hypoxemia generally has a more benign prognosis and responds as the underlying disease is controlled 1
• In patients with DAH and renal involvement (pulmonary-renal syndrome), aggressive immunosuppression is critical 1
• Before diagnosing refractory disease, ensure immunosuppression has been optimized and exclude mimics such as infection, medications, and malignancy 1
• Patients with refractory disease should be referred to centers with expertise in vasculitis 1

Monitoring and Follow-up

• Monitor for treatment response with clinical symptoms, oxygenation parameters, and radiographic improvement 1
• For patients with AAV, continue maintenance immunosuppression after remission to prevent relapse 1
• For kidney transplant candidates with history of AAV and DAH, delay transplantation until complete clinical remission for ≥6 months 1

Prognosis

• Hospital mortality for DAH can be high (27% in one series), with 42% of patients requiring ventilatory support 4
• After successful treatment of acute DAH, the long-term prognosis may be favorable with appropriate maintenance therapy 4
• Mortality risk is more closely associated with the rate of hemoptysis rather than the quantity 1