Hyperacute Lung Transplant Rejection

Epidemiology

  • Incidence: hyper acute lung transplant rejection has become a rare type of rejection (due to more sensitive and specific pre-transplant screening for HLA antibodies

Physiology

  • Reaction of Preformed Recipient Donor-Specific Antibodies, Usually Directed Against Foreign Donor Human Leukocyte Antigens (HLA)
    • Less commonly, antibodies may be directed against donor ABO blood group or endothelial antigens

Diagnosis

Chest X-Ray (see Chest X-Ray, [[Chest X-Ray]])

  • Diffuse reticular/ground-glass opacities

Ventilation-Perfusion (V/Q) Scan (see Ventilation-Perfusion Scan, [[Ventilation-Perfusion Scan]])

  • Helpful to rule out vascular anastomotic complications

Chest Computed Tomography (Chest CT) (see Chest Computed Tomography, [[Chest Computed Tomography]])

  • May be helpful

Transesophageal Echocardiogram (TEE) (see Echocardiogram, [[Echocardiogram]])

  • Useful to assess flow through pulmonary veins in the left atrium

Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])

  • Bronchoalveolar Lavage (BAL): useful to examine the bronchial anastomosis, assess for alveolar hemorrhage, and obtain microbiologic samples
  • Transbronchial Biopsy (TBB) (see Bronchoscopy, [[Bronchoscopy]]): risk of TBB may be prohibitive

Open Lung Biopsy

  • Marked neutrophilic interstital infiltrate, alveolar edema, small arteriolar platelet and fibrin thrombi -> alveolar capillaries are the primary target of injury in hyperacute rejection

Cross-Match Between Recipient Serum and Donor Cells Demontrating Incompatibility

  • Diagnostic

Presence of Pre-Transplant Donor-Specific Antibodies in Recipient’s Serum

  • Diagnostic

Clinical Manifestations

General Comments

  • Onset: min-hours (usually within 24 hrs post-transplant)

Cardiovascular Manifestations

Pulmonary Manifestations

  • Copious Pink Frothy Pulmonary Edema Fluid
  • Rapid Onset of Severe Hypoxemia/Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

Treatment

Supportive Care

Other

  • Anti-Thymocyte Globulin (ATG) (see Anti-Thymocyte Globulin, [[Anti-Thymocyte Globulin]])
  • Bortezomib (Velcade) (see Bortezomib, [[Bortezomib]]): proteasome inhibitor, which has pro-apoptotic effects on plasma cells -> decreases antibody synthesis
  • Corticosteroids (see Corticosteroids, [[Corticosteroids]]): while patients are typically receiving corticosteroids as part of their induction regimen, they are not believed to be useful in the management of hyperacute rejection
  • Cyclophosphamide (Cytoxan) (see Cyclophosphamide, [[Cyclophosphamide]])
  • Eculizumab (Soliris) (see Eculizumab, [[Eculizumab]]): anti-complement C5 antibody
  • Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin, [[Intravenous Immunoglobulin]]): causes B-lymphocyte apoptosis, blocks binding of donor-reactive antibodies, and inhibits complement activation
  • Plasmapheresis (see Plasmapheresis, [[Plasmapheresis]]): rapidly removes anti-donor antibodies from peripheral blood to prevent further allograft damage
  • Rituximab (Rituxan) (see Anti-CD20 Therapy, [[Anti-CD20 Therapy]]): B-lymphocyte depleting monoclonal antibody

Prognosis

  • High Mortality Rate

References

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