Hemosiderosis Workup

The following studies are indicated in pulmonary hemosiderosis (PH)

• CBC count

  • Microcytic and hypochromic anemia are present.
  • Eosinophilia has been present in approximately one eighth of reported cases. Most of these cases are associated with Heiner syndrome.
• Stool guaiac test results - Frequently positive
• Analysis of gastric lavages - Positive for iron-laden macrophages
• Immunoglobulin E level - High levels possible in Heiner syndrome
• Serologic analysis

  • Titers of serum precipitins to casein and lactalbumin are elevated in Heiner syndrome.
  • Circulating anti-GBM antibodies are present in patients with Goodpasture syndrome.
  • Antineutrophil cytoplasmic antibodies (C-ANCA) are present in patients with Wegener granulomatosis.
  • Antinuclear antibodies and anti-DNA antibodies are positive in systemic lupus erythematosus (SLE).
  • Serologic markers for celiac disease include gliadin antibodies and reticulin antibodies. If findings are positive, then consider performing a jejunal biopsy.
• Sputum analysis

  • Perform stain, culture, and sensitivity for bacteria, fungi, and mycobacteria.
  • Cytology may reveal hemosiderin-laden macrophages, which suggests bleeding during the preceding months and ongoing bleeding for more than 3-4 days.
• Urinalysis - Hematuria and/or proteinuria in pulmonary hemosiderosis secondary to immune-mediated glomerulonephritis, Goodpasture syndrome, and SLE
• Prothrombin time/activated partial thromboplastin time - Used to rule out bleeding disorders
• von Willebrand factor antigen and Ristocetin cofactor levels - May be obtained to assess for von Willebrand disease
• IgA antiendomysial antibody level - Facilitates the diagnosis of celiac disease (However, histologic examination of a duodenal biopsy sample remains the criterion standard.)

• Chest radiography

  • The most common finding is patchy alveolar infiltrates that are often perihilar or basilar and are usually bilateral. Infiltrates may be migratory.
  • Interstitial changes are found in long-standing pulmonary hemosiderosis.
  • Occasionally, chest radiograph findings may be normal.
  • Hilar lymph nodes may be enlarged, especially in the acute stage.
  • Resolution, often with a persistent reticular pattern, occurs in less than 2 weeks.
• CT scanning

  • May show areas of increased pulmonary density due to intra-alveolar hemorrhage and/or hemosiderin-laden macrophages, even when the chest radiograph findings appear normal
  • Useful in distinguishing superimposed infections from fresh hemorrhages
  • Helpful if focal pulmonary causes, endobronchial lesions, or vascular malformations are suspected
  • Useful in demonstrating the exact localization of lesions for open lung biopsy
• Nuclear scanning

  • The lungs of healthy patients do not take up RBCs labeled with chromium isotope (⁵¹ Cr) or technetium Tc 99 (⁹⁹ Tc) pertechnetate.
  • Scans with abnormal pulmonary uptake 12-24 hours after the injection have been observed in patients with pulmonary hemorrhage.
• Ventilation/perfusion scanning - Important if pulmonary embolism is suspected

• After an episode of acute hemorrhage, pulmonary function testing (PFT) demonstrates decreased compliance, airflow obstruction, and an increase in the diffusing capacity for carbon monoxide (due to increased hemoglobin uptake of carbon monoxide by sequestrated RBCs in the lungs).
• In long-standing pulmonary hemosiderosis, PFT results demonstrate a restrictive pattern.

• Flexible bronchoscopy

  • Performed to assess the anatomy of the airways for pulmonary malformations, endobronchial lesions, retained foreign body, and airway compression
  • Used to perform bronchoalveolar lavage (BAL)
• Bronchoalveolar lavage

  • Hemosiderin-laden macrophages: Hemosiderin-laden macrophages are diagnostic for PH. They are usually cleared from the alveoli and airways within a few months of the bleeding. The microphages are observed 2-3 days after acute bleeding.
  • Malignant cells in cases of neoplasms (extremely uncommon in pediatric patients)
  • Positive stains and cultures for bacteria, fungi, and mycobacteria in cases of infection
• Open lung biopsy

• Findings in the lung vary with the stage of the disease.
• In the early stages, interstitial and intra-alveolar hemorrhages predominate, with collections of both free hemosiderin and hemosiderin-laden macrophages found in the alveolar spaces and in the interstitium.
• As the disease progresses, interstitial fibrosis develops.
• Immunofluorescence and electron microscopy of the lung and kidney tissue may differentiate idiopathic pulmonary hemosiderosis (IPH) from Goodpasture syndrome and immune complex–mediated diseases.