Plasmapheresis (Plasma Exchange) Guidelines
Overview and Mechanism
Plasmapheresis is an extracorporeal blood purification procedure that removes pathogenic plasma components—including autoantibodies, immune complexes, paraproteins, and inflammatory mediators—while returning cellular blood components to the patient. 1 The removed plasma is replaced with albumin, fresh frozen plasma, or crystalloid solutions. 1
Primary Clinical Indications
Neurological Disorders
- First-line therapy for severe Guillain-Barré syndrome (high-quality evidence) 1
- Myasthenia gravis with significant symptoms (moderate-quality evidence) 1
- Severe immune-mediated neuropathies with rapid progression (low-quality evidence) 1
Renal Conditions
- ANCA-associated vasculitis requiring dialysis or with rapidly increasing serum creatinine (high-quality evidence) 1
- Anti-glomerular basement membrane (anti-GBM) disease (moderate-quality evidence) 1
- Severe cryoglobulinemia with acute kidney involvement (low-quality evidence) 1
- Diffuse pulmonary hemorrhage in ANCA vasculitis (high-quality evidence) 1
Hematological Disorders
- Symptomatic hyperviscosity due to paraproteinemia as first-line therapy (high-quality evidence) 1
- Preventive treatment before rituximab in patients with IgM ≥ 4 g/dL to avoid symptomatic IgM flares (moderate-quality evidence) 1
- Supportive treatment in multiple myeloma with high protein levels at risk for hyperviscosity syndrome 2
- Waldenström's macroglobulinemia, idiopathic thrombocytopenic purpura (ITP), pure red cell aplasia (PRCA) 2
- Thrombotic thrombocytopenic purpura (TTP) as first-choice treatment 2
Autoimmune Pulmonary Conditions
- Autoimmune pulmonary alveolar proteinosis (aPAP) refractory to other treatments: Use plasmapheresis for patients requiring high-flow supplemental oxygen (≥4L/min) or two or more whole lung lavages over one year despite receiving exogenous GM-CSF and rituximab, or having failed these treatments (conditional recommendation, very low certainty) 3
- Higher intensity plasmapheresis regimens may be needed to successfully suppress GM-CSF autoantibodies 1
Dermatological Conditions
- Bullous pemphigoid: Plasmapheresis removes pathogenic antibodies and inflammatory mediators 3
- In one controlled trial, plasmapheresis resulted in lower total steroid doses (1240 ± 728 mg vs. 2770 ± 1600 mg over 6 months) 3
- Refractory pemphigus vulgaris when combined with corticosteroids and immunosuppressants (moderate-quality evidence) 1
- Not recommended as routine treatment for newly diagnosed pemphigus but may be considered in refractory cases 1
Transplantation
- Antibody-mediated rejection (AMR) in liver transplantation: For patients with persistent high levels of pre-formed donor-specific antibodies (DSAs) post-transplant, plasmapheresis plus intravenous immunoglobulin is recommended to remove circulating IgG 3
- Combined acute T cell-mediated rejection and AMR: Treat T cell component first with steroid boluses; use plasmapheresis +/- IVIG for non-responders or those with pure acute AMR (LoE 4, open recommendation, strong consensus) 3
- Cardiac transplantation: Treatment option for antibody-mediated rejection (low-quality evidence) 1
- Immunomodulation in solid-organ transplant: Used pretransplant in allosensitized recipients to increase likelihood of successful match, and for ABO incompatible recipients 4
Other Autoimmune Conditions
- Severe immunotherapy-related toxicities, particularly neurologic adverse events (high-quality evidence) 1
- Catastrophic antiphospholipid syndrome (level V evidence) 5
- Systemic lupus erythematosus (SLE): In patients with high circulating immune complexes deteriorating despite corticosteroids, plasmapheresis may relieve blockade of the mononuclear phagocytic system 6
Critical Treatment Principles
Combination Therapy Requirements
Plasmapheresis should generally be combined with immunosuppressive medications to prevent rebound antibody production (moderate-quality evidence). 1 The procedure physically removes circulating antibodies but does not prevent their regeneration. 7
Timing Considerations
Rituximab must be administered AFTER plasmapheresis, not before, since the procedure removes the drug from circulation. 1 This timing is critical for therapeutic efficacy.
Safety Profile and Complications
Mortality Risk
The mortality associated with plasmapheresis is estimated at 0.05% based on systematic reviews (high-quality evidence). 8, 1
Common Complications
- Blood pressure instability due to rapid fluid shifts 8
- Coagulation defects from removal of clotting factors 8, 1
- Increased infection risk due to removal of immunoglobulins 8, 1
- Electrolyte disturbances (hypokalemia, hypocalcemia), usually mild 2
Severe Complications
- Pulmonary embolism (rare) 8
- Transfusion-related acute lung injury (TRALI) when using fresh frozen plasma 8
- Thrombosis 9, 1
- Hemodynamic shifts 9, 1
Replacement Fluid Considerations
- Fresh frozen plasma (FFP) carries risks of ABO incompatibility, infectious disease transmission, and allergic reactions 8
- Albumin replacement has fewer complications but does not replace specific clotting factors 8
- Selection should be based on the patient's condition and specific disease being treated 8
Special Population Considerations
Benefit-risk assessment must be carefully considered in hemodynamically unstable patients. 8 When combined with immunosuppressants, there is increased risk of opportunistic infections requiring prophylactic measures. 1
Practical Procedural Considerations
Evidence Quality Limitations
For many indications, particularly in autoimmune pulmonary conditions, the quality of evidence is very low and arises primarily from case reports. 3 Spontaneous remission occurs in some conditions, making treatment effects difficult to establish confidently. 3
Monitoring Requirements
When plasmapheresis is used, detection and monitoring of symptomatic disease-related circulating free antibodies or immune complexes is mandatory. 5
Procedure Safety
When performed by qualified staff, plasmapheresis is relatively safe and serious complications are very rare. 2 The procedure requires intravenous catheter access, which itself carries complication risks. 2