Double Filtration Plasmapheresis in Autoimmune Diseases
Double filtration plasmapheresis (DFPP) is indicated as a salvage therapy for refractory autoimmune diseases when conventional immunosuppression has failed, particularly in autoimmune pulmonary alveolar proteinosis, antibody-mediated rejection, severe ANCA vasculitis, and drug-resistant pemphigus, where it offers the advantage of selective antibody removal with minimal replacement fluid requirements compared to standard plasmapheresis. 1, 2
Primary Indications by Disease Category
Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
- Use DFPP/plasmapheresis only in patients with confirmed autoimmune PAP who remain significantly symptomatic requiring high-flow supplemental oxygen (≥4L/min) OR require two or more whole lung lavages over a year, despite receiving exogenous GM-CSF and rituximab, or having previously failed these treatments. 1
- This represents a conditional recommendation with very low certainty of evidence, positioning plasmapheresis as fourth-line therapy after whole lung lavage, GM-CSF, and rituximab. 1
Antibody-Mediated Rejection in Transplantation
- For cardiac transplant AMR with hemodynamic instability, initiate plasmapheresis immediately combined with methylprednisolone and immunosuppression—never use plasmapheresis as monotherapy. 2
- In liver transplant AMR, plasmapheresis plus intravenous immunoglobulin is suggested for patients who do not respond to steroid boluses or those with "pure" acute AMR according to Banff criteria. 1
- DFPP has demonstrated efficacy in pediatric kidney transplant antibody-mediated rejection, though outcomes vary (1 full recovery, 1 CKD stage 4 requiring dialysis in one series). 3
ANCA-Associated Vasculitis with Severe Renal Disease
- Add plasmapheresis for patients requiring dialysis OR with rapidly increasing serum creatinine, using 60 ml/kg volume replacement for 7-10 treatments total. 2
- For diffuse pulmonary hemorrhage in ANCA vasculitis, initiate plasmapheresis daily until bleeding stops, then every other day for a total of 7-10 treatments. 2
- Discontinue after 3 months in patients who remain dialysis-dependent without extrarenal manifestations, as continued therapy provides no additional benefit. 2
- DFPP showed comparable efficacy to immunoadsorption in anti-GBM disease (59.0% vs 71.2% antibody clearance, P=1.00) with fewer IgG losses and plasma-related side effects. 4
Drug-Resistant Pemphigus
- Consider DFPP for moderate to severe pemphigus physically and/or serologically unresponsive to 1.0 mg/kg per day prednisolone plus other supportive therapies. 5
- DFPP achieved 85.6±14.4% reduction in autoantibodies (P=0.00014) and 75.4±24.3% reduction in pemphigus disease area index (P=0.0023), allowing prednisolone dose reduction by 41±8.9 mg within 3 months. 5
- Standard plasmapheresis cannot be recommended as routine treatment in newly presenting pemphigus patients but may be considered in refractory cases when combined with corticosteroids and immunosuppressants. 1
Other Autoimmune Conditions
- DFPP has been used successfully in autoimmune hepatitis-SLE overlap resistant to massive corticosteroid therapy, though this represents anecdotal evidence. 6
- Pediatric experience includes successful treatment of myasthenia gravis, Guillain-Barré disease, and autoimmune limbic encephalitis with DFPP. 3
Technical Advantages of DFPP Over Standard Plasmapheresis
Mechanism and Selectivity
- DFPP uses two filters with different pore sizes: a plasma separator followed by a plasma component separator that selectively removes large molecular weight pathogenic substances while returning albumin and small molecules to the patient. 7
- This semi-selective approach significantly reduces replacement fluid volume compared to standard plasma exchange, minimizing blood product exposure. 3, 7
Clinical Outcomes
- In a 10-year pediatric series of 436 DFPP sessions in 23 patients, excluding FSGS patients with >100 sessions, only 1 patient required cryoprecipitate and 2 required blood transfusions—no other blood products were needed. 3
- Minor complications occurred in only 8.4% of sessions with no major complications, demonstrating excellent safety profile. 3
Critical Timing and Combination Therapy Protocols
Coordination with Immunosuppression
- Always administer corticosteroids concurrently with DFPP, as steroids are not significantly removed due to high protein binding. 8
- Give rituximab 48-72 hours AFTER the last plasmapheresis session to avoid drug removal from circulation. 2, 8
- Administer IVIG only AFTER plasmapheresis is complete, never before, as the procedure will immediately remove the immunoglobulin. 2, 8
Standard Treatment Protocols
- Standard plasma exchange involves exchanging twice the blood volume. 2
- Typical courses range from 2-6 sessions for neurologic conditions to daily exchanges for 5 days in cardiac AMR. 2
- For DFPP specifically, a double volume of plasma is processed with 30-40g human albumin supplement per session. 4
Safety Profile and Complication Management
Overall Risk Assessment
- Mortality associated with plasmapheresis is estimated at 0.05% based on systematic reviews of >15,500 patients. 2, 9
- Cochrane meta-analysis of 556 Guillain-Barré patients showed plasmapheresis did not increase risk of infection, blood pressure instability, cardiac arrhythmias, or pulmonary embolism. 2
Specific Complications to Monitor
- Blood pressure instability from rapid fluid shifts during the procedure. 9
- Coagulation defects from removal of clotting factors. 1, 8, 9
- Increased infection risk due to immunoglobulin removal. 8, 9
- Rare but serious complications include pulmonary embolism and transfusion-related acute lung injury (TRALI) when using fresh frozen plasma. 9
Replacement Fluid Considerations
- Fresh frozen plasma carries risks of ABO incompatibility, infectious disease transmission, and allergic reactions. 9
- Albumin replacement has fewer complications but does not replace specific clotting factors. 9
- DFPP's advantage is the dramatically reduced need for replacement fluids compared to standard plasmapheresis, minimizing these risks. 3, 7
Common Pitfalls and How to Avoid Them
Critical Errors to Prevent
- Never use plasmapheresis/DFPP as monotherapy—it must be combined with immunosuppression or the disease will recur due to rebound antibody production. 2, 8
- Do not give IVIG before or during plasmapheresis—this wastes expensive therapy as it will be immediately removed. 2, 8
- Do not withhold steroids during plasmapheresis thinking they will be removed—this delays necessary immunosuppression. 8
- Never use for dialysis-dependent vasculitis patients without extrarenal manifestations after 3 months of treatment. 2
Patient Selection Criteria
- Careful benefit-risk assessment should be performed in hemodynamically unstable patients. 9
- Plasmapheresis is well-tolerated in children with neurological disease, though procedural risks are higher than in adults. 2