Diffuse Alveolar Hemorrhage

Diffuse alveolar haemorrhage (DAH) is bleeding into the alveolar spaces from the alveolar capillaries, causing diffuse pulmonary infiltrates, hypoxaemia and often anaemia.

Causes

• Immune mediated capillaritis: ANCA associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, EGPA), anti GBM disease, systemic lupus erythematosus, antiphospholipid syndrome, IgA vasculitis, cryoglobulinaemia, rheumatoid arthritis, Behçet disease, mixed connective tissue disease.
• Non capillaritis (bland haemorrhage): mitral stenosis, left heart failure, coagulopathy, drugs (amiodarone, nitrofurantoin, propylthiouracil, anticoagulants, cocaine crack, rituximab), idiopathic pulmonary haemosiderosis, haematopoietic stem cell transplant, infections (leptospirosis, hantavirus, influenza), inhalation (trimellitic anhydride), acute lung injury.
• Pulmonary veno occlusive disease, capillary haemangiomatosis. Mortality 25 to 50% in mechanically ventilated patients; high rates of recurrence in vasculitis.

• Dyspnoea, cough, haemoptysis (absent in up to 33% despite severe bleeding), fever, chest pain.
• Hypoxaemic respiratory failure over days, with anaemia and bilateral crackles.
• Features of underlying disease: sinusitis, haematuria, rash, arthritis, neuropathy, livedo, history of anticoagulant use.

• Chest radiograph/CT: bilateral ground glass and consolidation, central and basal predominance, sparing of apices and costophrenic angles; crazy paving later.
• Falling haemoglobin; iron deficiency late; raised DLCO (not done in unstable patients).
• Bronchoscopy with bronchoalveolar lavage: progressively bloody return in sequential aliquots, haemosiderin laden macrophages (over 20% of macrophages, appearing after 48 to 72 hours).
• Serology: ANCA (MPO, PR3), anti GBM, ANA, anti dsDNA, complement (C3, C4), antiphospholipid antibodies, cryoglobulins, rheumatoid factor, anti CCP.
• Urinalysis, creatinine; renal biopsy for pulmonary renal syndrome; surgical lung biopsy only if non diagnostic.
• Exclude infection (cultures, viral PCR, leptospirosis serology), coagulation tests, echocardiography, drug and toxin review.

• Supportive care first: oxygen, intubation and lung protective ventilation (high PEEP tamponades bleeding), correct coagulopathy and anaemia, discontinue anticoagulants and offending drugs, ECMO (without heparin or low dose) for refractory hypoxaemia.
• Immunosuppression for capillaritis (after excluding infection):
  • Methylprednisolone 500 to 1000 mg IV daily for 3 days, then prednisolone 1 mg/kg.
  • Rituximab 375 mg/m2 weekly for 4 doses or 1 g on days 1 and 15, or cyclophosphamide 15 mg/kg IV (or 2 mg/kg orally) for ANCA vasculitis and lupus.
  • Plasma exchange (7 exchanges over 14 days) for anti GBM disease, severe pulmonary renal syndrome with creatinine over 300 µmol/L, or refractory DAH; avacopan 30 mg twice daily as steroid sparing in ANCA vasculitis.
• Recombinant activated factor VII (off label) or intrapulmonary desmopressin/tranexamic acid have been used in refractory bleeding (limited evidence).
• Treat cause in non capillaritis: diuretics and valve surgery for mitral stenosis, reverse anticoagulation (vitamin K, prothrombin complex), treat infection.
• Maintenance immunosuppression: azathioprine 2 mg/kg or rituximab maintenance (500 mg every 6 months) for 18 to 24 months.
• Pneumocystis prophylaxis during therapy; monitor for relapse.