What is the indication for double filtration plasmapheresis (DFPP) in patients with autoimmune diseases?

Double Filtration Plasmapheresis: Clinical Indications in Autoimmune Diseases

Double filtration plasmapheresis (DFPP) serves as a selective antibody-removal technique indicated primarily for specific autoimmune conditions that have failed standard therapies, including refractory autoimmune pulmonary alveolar proteinosis, transplant antibody-mediated rejection, severe ANCA-associated vasculitis with renal failure, anti-GBM disease, and drug-resistant pemphigus. 1

Primary Disease-Specific Indications

Autoimmune Pulmonary Alveolar Proteinosis (aPAP)

• Use DFPP only in confirmed aPAP patients who remain significantly symptomatic requiring high-flow supplemental oxygen OR require two or more whole lung lavages per year, despite receiving exogenous GM-CSF and rituximab or having previously failed these treatments 1
• DFPP represents fourth-line therapy after whole lung lavage, GM-CSF, and rituximab for aPAP 1
• This is a conditional recommendation with very low certainty of evidence, so reserve for truly refractory cases 1

Transplant Antibody-Mediated Rejection (AMR)

• For cardiac transplant AMR with hemodynamic instability, initiate DFPP immediately combined with methylprednisolone and immunosuppression—never use as monotherapy 1, 2
• In one series of 12 hemodynamically unstable AMR patients treated with plasma exchange plus methylprednisolone, 1-year and 5-year survival were 75% and 51% respectively 2
• For liver transplant AMR patients who do not respond to steroid boluses or those with "pure" acute AMR according to Banff criteria, use DFPP plus intravenous immunoglobulin 1

ANCA-Associated Vasculitis with Severe Renal Disease

• Add DFPP for patients requiring dialysis or with rapidly increasing serum creatinine, using 60 ml/kg volume replacement for 7-10 treatments total 1, 2
• For diffuse pulmonary hemorrhage in ANCA vasculitis, initiate DFPP daily until bleeding stops, then every other day for a total of 7-10 treatments 2
• Discontinue treatment after 3 months in patients who remain dialysis-dependent without extrarenal manifestations 2

Anti-Glomerular Basement Membrane Disease

• DFPP efficiently and safely removes anti-GBM antibodies with 59% efficacy in clearing antibodies, comparable to immunoadsorption 3
• In a series of patients with anti-GBM disease treated with DFPP, clinical outcomes showed similar patient survival and renal survival compared to immunoadsorption, with fewer plasma-associated side effects 3
• DFPP may be particularly advantageous in patients with insufficient plasma availability for standard plasma exchange 3

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 1
• DFPP achieved 85.6% reduction in autoantibodies and 75.4% reduction in pemphigus disease area index, allowing prednisolone dose reduction by 41 mg approximately 3 months after treatment 4
• This is not a routine recommendation but reserved for truly refractory cases 1

Other Autoimmune Conditions

• DFPP has been successfully used in pediatric patients with recurrent focal segmental glomerulosclerosis, Myasthenia Gravis, Guillain-Barré disease, and autoimmune limbic encephalitis 5
• For autoimmune hepatitis resistant to or intolerant of massive corticosteroid therapy, DFPP combined with immunosuppressive therapies can produce remarkable improvement 6

Technical Advantages Over Standard Plasmapheresis

• DFPP uses two filters with different pore sizes, selectively removing large molecular weight pathogenic substances while returning albumin and small molecules to the patient, significantly reducing replacement fluid volume compared to standard plasma exchange 1, 7
• The plasma separator first separates blood into plasma and blood cells, then the plasma component separator fractionates plasma into large and small molecular weight components 7
• Large molecular weight components including pathogenic antibodies are discarded, while valuable substances like albumin are returned 7
• This selectivity reduces the need for replacement blood products—in a 10-year pediatric series of 436 sessions, excluding FSGS patients, only one patient required cryoprecipitate and two required blood transfusions 5

Critical Timing with Combination Therapies

Corticosteroids

• Always administer corticosteroids concurrently with DFPP, as steroids are not significantly removed due to high protein binding 1
• Do not withhold steroids during DFPP thinking they will be removed—this delays necessary immunosuppression 1

Rituximab

• Give rituximab 48-72 hours AFTER the last DFPP session to avoid drug removal from circulation 1, 2
• Administering rituximab before or during DFPP wastes the medication as the procedure removes it 2

Intravenous Immunoglobulin (IVIG)

• Administer IVIG only AFTER DFPP is complete, never before, as the procedure will immediately remove the immunoglobulin 1, 2
• This timing coordination is essential to avoid wasting expensive IVIG therapy 1

Safety Profile

• Mortality associated with DFPP is estimated at 0.05% based on systematic reviews of >15,500 patients 1, 2, 8
• In a pediatric series of 436 sessions, minor complications occurred in only 8.4% of sessions with no major complications 5
• DFPP does not increase risk of infection, blood pressure instability, cardiac arrhythmias, or pulmonary embolism based on Cochrane meta-analysis 1
• Potential complications include coagulation defects from removal of clotting factors 1, 8
• Blood pressure instability can occur due to rapid fluid shifts 8
• DFPP results in less IgG loss compared to standard plasma exchange (62.7% vs. 83.5% reduction), potentially reducing infection risk 3

Critical Pitfalls to Avoid

• Never use DFPP as monotherapy—it must be combined with immunosuppression or the disease will recur due to rebound antibody production 1, 2
• Do not give IVIG before or during DFPP—this wastes expensive therapy as it will be immediately removed 1
• Do not withhold corticosteroids during DFPP thinking they will be removed—steroids have high protein binding and are not significantly cleared 1
• Do not administer rituximab before completing the DFPP course—wait 48-72 hours after the last session 1, 2