Diffuse Alveolar Hemorrhage (DAH)

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary syndrome characterized by:

• Bleeding into the alveolar spaces
• Damage to the alveolar-capillary basement membrane
• Resulting in:
• Hemoptysis
• Diffuse pulmonary infiltrates
• Acute hypoxemic respiratory failure
• Falling hemoglobin

DAH is not a single disease, but a manifestation of multiple disorders causing injury to pulmonary microcirculation:

Pathophysiology

Normal Alveolar-Capillary Barrier

The barrier consists of:

1. Alveolar epithelium
2. Basement membrane
3. Capillary endothelium

When disrupted:

• RBCs leak into alveoli
• Gas exchange is impaired
• Surfactant dysfunction occurs
• Inflammatory cascade activates
• Acute respiratory failure develops

Histopathologic Patterns of DAH with Etiology

1. Pulmonary Capillaritis (Most Common)

Neutrophilic inflammation destroying alveolar capillaries.

Histology

• Neutrophilic infiltration
• Fibrinoid necrosis
• Interstitial inflammation
• RBC extravasation
• Hemosiderin-laden macrophages

Mechanism –Immune-mediated small vessel vasculitis.

ANCA-associated vasculitis

• Granulomatosis with polyangiitis (GPA)
• Microscopic polyangiitis (MPA)
• Eosinophilic granulomatosis with polyangiitis (EGPA)

Anti-GBM disease

SLE

IgA vasculitis

Cryoglobulinemia

Drug-induced vasculitis

2. Bland Pulmonary Hemorrhage

Alveolar bleeding WITHOUT inflammation or capillary destruction.

• Anticoagulants
• Coagulopathy
• Mitral stenosis
• Elevated pulmonary venous pressure
• DIC
• Thrombocytopenia
• ECMO-related bleeding

Histology

• Intra-alveolar RBCs
• Minimal inflammation

3. Diffuse Alveolar Damage with Hemorrhage

• ARDS
• Inhalational injury
• Severe infection
• Toxic injury

Histology:

• Hyaline membranes
• Edema
• Hemorrhage

Infection-Associated DAH

• Influenza
• Dengue
• Leptospirosis
• Malaria
• Hantavirus
• CMV
• Invasive aspergillosis
• Severe bacterial pneumonia

 Transplant-Associated

• Bone marrow transplantation
• Hematopoietic stem cell transplantation

 Other Causes

• Idiopathic pulmonary hemosiderosis
• Acute silicosis
• High altitude pulmonary edema
• Fat embolism syndrome

Clinical Features

Classical Triad

1. Hemoptysis
2. Diffuse infiltrates
3. Falling hemoglobin

BUT:

• Hemoptysis may be absent in up to one-third.

Symptoms

Respiratory

• Dyspnea
• Cough
• Hemoptysis
• Hypoxemia
• Tachypnea

Constitutional

• Fever
• Malaise
• Weight loss

Renal symptoms

Suggest pulmonary-renal syndrome:

• Hematuria
• Oliguria
• Edema

Physical Examination

Respiratory findings

• Crackles
• Respiratory distress
• Cyanosis

Vasculitic clues

• Purpura
• Sinus disease
• Nasal ulcers
• Mononeuritis multiplex

SLE clues

• Malar rash
• Arthritis

Diagnosis of DAH

Suspect DAH in:

• Acute hypoxemia
• Bilateral infiltrates
• Falling Hb
• Hemoptysis
• Vasculitic symptoms

Initial Investigations

CBC

• Falling Hb
• Leukocytosis
• Thrombocytopenia

ABG

• Hypoxemia
• Increased A-a gradient

Chest X-ray

• Bilateral diffuse alveolar infiltrates
• Central/perihilar opacities
• Rapidly changing shadows

HRCT Thorax

• Bilateral ground-glass opacities
• Consolidation
• Crazy paving
• Diffuse distribution

Bronchoscopy with BAL (main test)

Sequential BAL aliquots become progressively bloodier.

Example:

• First lavage: pink
• Second: red
• Third: dark bloody

This strongly suggests DAH.

Hemosiderin-Laden Macrophages

Detected using: Prussian blue staining

Suggest prior alveolar bleeding.

Typically appear after: 48–72 hours

Bronchoscopy Also Helps Exclude

• Infection
• Malignancy
• Eosinophilic lung disease

Serological Workup

Vasculitis panel-c-ANCA (PR3),p-ANCA (MPO)

Autoimmune workup

• ANA,dsDNA,Complement levels

Anti-GBM antibodies

APS testing

• Lupus anticoagulant
• Anticardiolipin antibodies

Urinalysis

Important for pulmonary-renal syndrome.

Findings:

• RBC casts
• Proteinuria
• Hematuria

Lung Biopsy

Rarely required.

Indications:

• Uncertain diagnosis
• Serology negative
• Nonresolving disease

Differential Diagnosis

Management of DAH

-Lung-protective ventilation

-Platelet/FFP

Antifibrinolytics

• Tranexamic acid
• Aminocaproic acid