Plasmapheresis and Plasma Exchange: High-Yield Information
Are They the Same Thing?
Yes, plasmapheresis and therapeutic plasma exchange (TPE) are the same procedure—both terms refer to the extracorporeal removal of plasma containing pathogenic elements while returning cellular components to the patient. 1, 2, 3
Core Mechanism
Plasma exchange mechanically removes circulating antibodies, immune complexes, complement components, cytokines, and adhesion molecules through extracorporeal separation using membrane filtration or centrifugation. 1, 4
The removed plasma is replaced with albumin (most common in the US), fresh-frozen plasma, or crystalloid solutions before reinfusion. 1, 2, 3
Plasma exchange is nonselective and removes all proteins, whereas immunoadsorption plasmapheresis selectively removes only immunoglobulins—but immunoadsorption is less widely available and less efficient at removing soluble cytokines. 1, 5
Critical Timing Principles with Other Medications
What Gets Removed vs. What Doesn't
Steroids (methylprednisolone, prednisone) are NOT significantly removed by plasma exchange due to high protein binding and tissue distribution—administer steroids concurrently with plasma exchange, not after. 6
Large molecules ARE removed: immunoglobulins, rituximab, and IVIG are all cleared by plasma exchange. 6
Medication Sequencing Algorithm
Corticosteroids: Give DURING plasma exchange sessions (not removed, work synergistically). 6
IVIG: Give AFTER all plasma exchange sessions are complete (will be removed if given before/during). 2, 7, 6
Rituximab: Administer 48-72 hours AFTER the last plasma exchange session (procedure removes the drug). 2, 6
Cyclophosphamide: Give immediately AFTER individual plasma exchange sessions. 6
Standard Treatment Protocol
Perform 5-7 plasma exchange sessions over 10-14 days, exchanging 1-1.5 plasma volumes per session. 1, 2, 6
Each session typically exchanges twice the blood volume (approximately 5% of body weight). 1
For severe acute conditions, daily plasma exchange for 5-7 days is standard, then transition to every other day if needed. 1
Primary Indications by Category
Category I: First-Line Therapy (Highest Evidence)
Guillain-Barré syndrome (severe): First-line therapy per American Academy of Neurology. 2
Symptomatic hyperviscosity from paraproteinemia: First-line per American Society of Hematology. 2
ANCA-associated vasculitis requiring dialysis or rapidly increasing creatinine: Recommended by American Society of Nephrology. 2
Diffuse pulmonary hemorrhage in ANCA vasculitis: High-quality evidence from European Respiratory Society. 2
Thrombotic thrombocytopenic purpura (TTP): First-choice treatment, not just supportive. 3
Category II: Adjunctive Therapy (Moderate Evidence)
Myasthenia gravis with significant symptoms: Moderate evidence per American Academy of Neurology. 2
Anti-GBM disease (Goodpasture's syndrome): Moderate evidence, well-established benefit. 2, 8
Antibody-mediated rejection in cardiac transplantation: Always combined with immunosuppression (methylprednisolone 1g daily × 3 days + modification of baseline immunosuppression). 1, 2
Pemphigus vulgaris/pemphigoid: Effective when combined with corticosteroids and immunosuppressants in refractory cases, but NOT recommended as routine first-line therapy. 1, 2, 8
Category III: Refractory/Severe Cases Only
Multiple myeloma with hyperviscosity syndrome: Supportive treatment when protein levels threaten hyperviscosity. 3
Waldenström's macroglobulinemia: Preventive treatment before rituximab if IgM ≥4 g/dL to avoid symptomatic flares. 2, 3
Severe immunotherapy-related neurologic toxicities: Consider methylprednisolone 1g daily × 5 days with plasma exchange for grade 3-4 checkpoint inhibitor-related Guillain-Barré. 2, 7
Critical Rule: Never Use as Monotherapy
Plasma exchange must be combined with immunosuppressive medications to prevent rebound antibody production—there is no support for monotherapy in autoimmune conditions. 1, 2
The standard combination is plasma exchange + high-dose corticosteroids + immunosuppressant modification (e.g., switching cyclosporine to tacrolimus, azathioprine to mycophenolate or cyclophosphamide). 1
Without concurrent immunosuppression, antibody production rebounds rapidly after plasma exchange ends. 1, 2
Mortality and Major Complications
Overall mortality: 0.05% based on systematic reviews. 2
Coagulation defects: Removal of clotting factors can cause bleeding, especially with concurrent anticoagulation or invasive procedures within 48 hours. 1, 2
Fibrinogen depletion: Use fibrinogen concentrate (3-4g or 50mg/kg) or cryoprecipitate (15-20 units in 70kg adult) for replacement—fresh frozen plasma is impractical for raising fibrinogen above 1.5 g/L. 2
Infection risk: Significantly increased when combined with immunosuppressants, requiring prophylaxis for opportunistic infections. 2, 6
Hemodynamic shifts and thrombosis: Monitor closely during sessions. 2
Sepsis: Four deaths from sepsis occurred in the plasma exchange group in one randomized trial of pemphigus, highlighting infection risk. 1
Common Pitfalls to Avoid
Do NOT give IVIG before or during plasma exchange—this wastes expensive therapy as it will be immediately removed. 2, 7, 6
Do NOT withhold steroids during plasma exchange thinking they will be removed—this delays necessary immunosuppression and steroids are not significantly cleared. 6
Do NOT use plasma exchange as monotherapy—always combine with immunosuppression to prevent antibody rebound. 1, 2
Do NOT use plasma exchange routinely in newly diagnosed pemphigus—reserve for refractory cases only. 1, 2
Do NOT administer rituximab immediately after plasma exchange—wait 48-72 hours to avoid drug removal. 2, 6
Variant Modalities
Double-filtration plasmapheresis and immunoadsorption plasmapheresis exist, but standard plasma exchange is favored in the United States due to lower cost and ease of use. 1
Immunoadsorption avoids need for replacement fluids and has superior safety profile compared to plasma exchange, but is less widely available. 1, 5
In Germany, immunoadsorption increasingly replaces plasma exchange due to equivalent efficacy with better safety. 5