Is plasmapheresis (plasma exchange) a viable treatment option?

Plasmapheresis as a Treatment Option: When and How to Use It

Plasmapheresis should not be used as a first-line treatment option but may be considered in refractory cases when conventional therapies have failed, particularly when combined with corticosteroids and immunosuppressant drugs. 1

Appropriate Clinical Indications

Plasmapheresis has specific indications where evidence supports its use:

Recommended Uses:

• Refractory autoimmune conditions where antibody-mediated disease persists despite standard therapy
• Severe autoimmune PAP (pulmonary alveolar proteinosis) in patients who:
  • Remain significantly symptomatic
  • Require high flow supplemental oxygen (≥4L/min)
  • Need two or more whole lung lavages over a year
  • Have failed GM-CSF and rituximab treatments 1
• Antibody-mediated autoimmune diseases with acute presentation requiring rapid antibody removal
• Neurologic conditions such as myasthenia gravis and Guillain-Barré syndrome (as first-line therapy) 1

Not Recommended For:

• Newly diagnosed pemphigus (no additional clinical benefit over standard therapy) 1
• First-line treatment in most autoimmune conditions where slower-acting immunosuppressive therapy is appropriate

Efficacy and Evidence Quality

The evidence supporting plasmapheresis is generally of low quality:

• Most data comes from case reports and small case series 1
• A randomized study in pemphigus showed no additional benefit of plasmapheresis over oral corticosteroids alone 1
• Four deaths from sepsis occurred in the plasmapheresis group in one pemphigus study 1
• Clinical benefits are often subjective and not based on validated measurement instruments 1

In refractory cases, however, some evidence suggests benefit:

• 4 of 9 cases reported significant symptomatic improvement in autoimmune PAP 1
• Significant reduction in GM-CSF antibody titers was reported in 5/9 cases 1
• Higher intensity plasmapheresis regimens appear more successful at suppressing autoantibodies 1

Safety Considerations

Plasmapheresis carries important safety considerations:

Common Complications (frequency):

• Fall in arterial blood pressure (8.4% of procedures)
• Arrhythmias (3.5%)
• Sensations of cold with temporarily elevated temperature (1.1%)
• Paresthesias (1.1%) 2

Severe Complications (2.16% of procedures):

• Shock
• Severe hypotension requiring vasopressors
• Persistent arrhythmias
• Hemolysis 2

Mortality:

• Estimated at 0.05% based on systematic review of >15,500 patients 1, 2

Additional Risks:

• Removal of important plasma proteins including clotting factors 1
• Potential coagulation defects 1
• Potential rebound production of autoantibodies after treatment 1

Implementation Protocol

When using plasmapheresis:

1. Always combine with immunosuppressive therapy to prevent rebound antibody production 1

2. Consider monitoring:

   • Clotting factors
   • Blood pressure during procedure
   • Cardiac rhythm
   • Temperature
   • Antibody titers when applicable

3. Prophylactic measures:

   • Consider calcium supplementation during procedure to prevent hypocalcemia
   • Monitor for signs of infection
   • Ensure adequate vascular access

Clinical Decision Algorithm

1. First attempt standard therapies:

   • Corticosteroids
   • Immunosuppressive agents
   • Disease-specific first-line treatments

2. Consider plasmapheresis if:

   • Patient has failed standard therapies
   • Disease is antibody-mediated
   • Rapid removal of antibodies is needed
   • Patient can tolerate the procedure

3. Always combine with:

   • Corticosteroids
   • Immunosuppressive drugs to prevent antibody rebound 1

4. Monitor response:

   • Clinical symptoms
   • Antibody titers when applicable
   • Need for repeat procedures

Conclusion

Plasmapheresis remains a specialized treatment option with specific indications. The evidence supporting its use is generally low quality, but it may provide benefit in carefully selected refractory cases when combined with appropriate immunosuppressive therapy. The procedure is generally well-tolerated with a low mortality rate, though common complications should be anticipated and managed appropriately.