What is the treatment for diffuse alveolar hemorrhage?

Treatment of Diffuse Alveolar Hemorrhage

Immediately initiate high-dose intravenous glucocorticoids plus rituximab (preferred) or cyclophosphamide without waiting for diagnostic confirmation when DAH with hypoxemia is suspected, as delayed treatment dramatically worsens outcomes. 1, 2

Immediate Immunosuppressive Therapy

The cornerstone of DAH treatment is aggressive early immunosuppression, particularly when immune-mediated causes (ANCA-associated vasculitis, anti-GBM disease, connective tissue disease) are suspected. 1, 3

Glucocorticoid Dosing Protocol

Pulse therapy (Days 1-3): 1, 2

• Administer IV methylprednisolone 500-1000 mg/day for 3 consecutive days 1, 3
• Maximum cumulative dose: 3 grams 1, 2

Transition to oral prednisone (weight-based): 1, 2

• Body weight <50 kg: 50 mg/day 1, 3
• Body weight 50-75 kg: 60 mg/day 1, 2
• Body weight >75 kg: 75 mg/day 1

Tapering schedule: 1

• Taper to reach 5 mg/day by weeks 19-52 1, 2

Immunosuppressive Agent Selection

Rituximab is preferred over cyclophosphamide when combined with glucocorticoids for remission induction. 1, 3 This recommendation comes from the American College of Rheumatology and EULAR guidelines, reflecting superior efficacy and safety profiles in recent trials. 1, 2

Maintenance therapy: 1, 2

• Continue immunosuppression for 18 months to 4 years after remission to prevent relapse in ANCA-associated vasculitis 1, 3

Plasma Exchange Indications

Consider plasma exchange for DAH with hypoxemia when any of the following are present: 1, 2

• Serum creatinine >3.4 mg/dL (>300 μmol/L) 1, 3
• Patient requires dialysis 1, 2
• Concomitant anti-GBM disease 1, 3

Important caveat: The 2024 PEXIVAS trial (191 patients with DAH, 61 with hypoxemia) showed no clinically relevant mortality benefit for plasma exchange in the primary composite outcome. 3 However, guidelines still conditionally recommend considering it for critically ill patients not responding to standard therapy, particularly those with anti-GBM disease where delayed treatment results in 96% mortality. 2

Ventilator Management for Severe Cases

Use lung-protective ventilation strategies to avoid worsening hemorrhage: 1, 2

Ventilator settings: 1, 3

• Tidal volumes: 6-8 mL/kg predicted body weight 1, 2
• Plateau pressure: ≤30 cmH₂O 1, 3
• Moderate PEEP: 6-8 cmH₂O to maintain oxygenation 1, 2

Avoid aggressive recruitment maneuvers: Continuous positive airway pressure at 35 cmH₂O can increase intracranial pressure and decrease cerebral perfusion, and may extend capillary damage. 1, 2

Critical Contraindications

Do not perform chest physiotherapy maneuvers in active DAH: 2, 3

• Manual hyperinflation can precipitate hemodynamic collapse from large intrathoracic pressure fluctuations 2
• Postural drainage with head-down positioning increases pulmonary blood flow to damaged areas 2
• Percussion and vibratory shaking cause direct mechanical trauma to hemorrhaging tissue 2
• Forced expiration techniques generate high intrathoracic pressures that propagate bleeding 2

Monitoring Treatment Response

Track the following parameters to assess bleeding control and treatment efficacy: 1, 3

Oxygenation: 1, 2

• PaO₂/FiO₂ ratio improvement as primary parameter 1, 3

Imaging: 1, 3

• Serial chest imaging for resolution of ground-glass opacities and consolidation 1, 2

Clinical symptoms: 1

• Dyspnea and hemoptysis (though mortality correlates more with rate than quantity of hemoptysis) 1, 2

Etiology-Specific Considerations

Anti-GBM Disease

This requires the most aggressive approach: 2

• Combine cyclophosphamide, glucocorticoids, and plasmapheresis immediately 2
• Delayed treatment results in 96% mortality 2
• Even patients presenting on dialysis may benefit from treatment if acute presentation with favorable biopsy features 2

ANCA-Associated Vasculitis

DAH occurs in approximately 25% of AAV patients: 1, 3

High mortality risk factors: 1, 2

• Older age 1
• Severe kidney failure 1
• Degree of hypoxemia 1
• Involvement of >50% of lung area 1

Infection risk: Infection is the leading cause of death (48%) within the first year, emphasizing the need to balance aggressive immunosuppression against infection risk. 1 The reduced-dose glucocorticoid regimen from PEXIVAS resulted in 40% less cumulative steroid exposure with similar efficacy and decreased infection risk. 2

Adjunctive Therapies

Avacopan: 2, 3

• Consider as adjunctive therapy to reduce glucocorticoid exposure in patients at high risk for steroid toxicity 2

Thromboprophylaxis: 2

• Commence standard venous thromboprophylaxis as soon as bleeding is controlled, as patients rapidly develop a prothrombotic state 2

Common Pitfalls to Avoid

Do not delay treatment waiting for diagnostic confirmation: 2, 3

• Begin empiric immunosuppressive therapy immediately when immune-mediated DAH is suspected 3
• Delaying bronchoscopy to confirm diagnosis worsens outcomes 2

Do not use lower starting glucocorticoid doses in life-threatening DAH: 2

• Doses <0.5 mg/kg/day are inadequate for organ- or life-threatening manifestations 2

Refer refractory cases immediately: 2, 3

• Patients not responding to standard therapy should be transferred to centers with vasculitis expertise 3