What is the role of plasmapheresis in clinical practice?

Plasmapheresis in Clinical Practice

Overview and Mechanism

Plasmapheresis is a therapeutic extracorporeal procedure that mechanically removes circulating antibodies, immune complexes, and pathogenic proteins from plasma, with established efficacy in specific autoimmune and hematologic conditions but requiring careful patient selection and risk-benefit assessment. 1

The procedure involves extracorporeal separation of plasma from cellular blood components through membrane filtration or centrifugation, with blood reconstituted using albumin, fresh-frozen plasma, or crystalloid before reinfusion 1. Plasma exchange nonselectively removes proteins, while immunoadsorption plasmapheresis selectively targets immunoglobulins, though the latter is less widely available 1.

Primary Clinical Indications

Category I: First-Line Therapy

Thrombotic Thrombocytopenic Purpura (TTP)

• Plasmapheresis is the treatment of choice for TTP, with daily plasma exchange continued for 14 days or until antibodies become undetectable 2, 3
• Should not be delayed while awaiting ADAMTS13 confirmation when clinical suspicion is high 2
• In pediatric patients, deferring plasmapheresis for 24-48 hours until ADAMTS13 results are available may be reasonable due to lower TTP incidence and higher procedural risks 2

Hyperviscosity Syndrome

• Plasmapheresis is definitive treatment for hyperviscosity due to macroglobulinemia 3

Category II: Adjunctive Therapy with Strong Evidence

ANCA-Associated Vasculitis with Severe Renal Disease

• Recommend adding plasmapheresis for patients requiring dialysis or with rapidly increasing serum creatinine 1
• The MEPEX trial demonstrated benefit in patients with rapidly progressive glomerulonephritis and serum creatinine ≥5.8 mg/dL, though longer-term analyses have raised questions about sustained benefit 1
• Suggest adding plasmapheresis for diffuse pulmonary hemorrhage, despite evidence coming only from retrospective studies 1
• Discontinue cyclophosphamide after 3 months in dialysis-dependent patients without extrarenal manifestations 1

Goodpasture's Syndrome (Anti-GBM Disease)

• Plasmapheresis is useful for glomerulonephritis associated with hemoptysis, targeting removal of pathogenic antiglomerular basement membrane antibodies 3

Cardiac Transplant Antibody-Mediated Rejection (AMR)

• Plasmapheresis combined with immunosuppression (not as monotherapy) is standard for AMR management 1
• In one series of 12 hemodynamically unstable AMR patients treated with plasma exchange (twice blood volume daily for 5 days) plus methylprednisolone, 1-year and 5-year survival were 75% and 51% respectively 1
• Used for desensitization in highly sensitized patients awaiting transplantation and to facilitate transplantation across positive crossmatches 1

Category III: Conditional/Salvage Therapy

Autoimmune Pulmonary Alveolar Proteinosis (aPAP)

• Suggest plasmapheresis only for patients with confirmed aPAP who remain significantly symptomatic (requiring ≥4L/min supplemental oxygen or ≥2 whole lung lavages per year) despite receiving or having failed GM-CSF and rituximab 1
• Evidence quality is very low, based only on 9 case reports with mixed results: 3/9 showed no benefit, 2/9 showed transient improvement, and 4/9 showed significant improvement 1
• Higher intensity regimens appear more successful at suppressing GM-CSF autoantibodies 1

Other Immune Hematologic Conditions

• Hemolytic disease of the newborn, HIV-associated autoimmune thrombocytopenic purpura, coagulation factor inhibitors, and catastrophic antiphospholipid syndrome have Level V evidence supporting use 4
• Post-transfusion purpura, heparin-induced thrombocytopenia type II, and autoimmune hemolytic anemia are considered experimental indications requiring detection of symptomatic disease-related circulating antibodies 4

Myasthenia Gravis and Guillain-Barré Syndrome

• Plasmapheresis is useful in myasthenia gravis management 3
• For Guillain-Barré disease, 2-6 sessions of plasmapheresis are employed 1

Technical Considerations

Procedure Protocols

• Standard plasma exchange involves exchanging twice the blood volume 1
• Typical courses range from 2-6 sessions for neurologic conditions to daily exchanges for 5 days in cardiac AMR 1
• Replacement fluids include albumin (fewer complications but doesn't replace clotting factors) or fresh-frozen plasma (replaces clotting factors but carries transfusion risks) 5

Drug Interactions

• Critical timing consideration: Plasmapheresis removes rituximab, so rituximab must be administered after plasmapheresis completion 1, 5, 2
• Sustained depletion of immunoglobulins and immune complexes requires concomitant immunosuppressive therapy 3

Safety Profile and Complications

Mortality and Serious Complications

• Overall mortality is estimated at 0.05% based on systematic reviews of >15,500 patients 1, 5, 6, 2
• Life-threatening episodes (shock, persistent arrhythmias, hemolysis) occur in 2.16% of procedures 7

Common Complications

• Hemodynamic instability: Blood pressure changes occur in 8.4% of procedures due to rapid fluid shifts 5, 7
• Cardiac arrhythmias: Occur in 3.5% of procedures 7
• Coagulation defects: Result from removal of clotting factors 5, 6
• Infection risk: Increased due to immunoglobulin removal 5, 6, 2
• Other: Cold sensations, paresthesias (1.1% each), pulmonary embolism (rare but serious) 5, 7

Replacement Fluid-Specific Risks

• Fresh-frozen plasma carries risks of ABO incompatibility, infectious disease transmission, allergic reactions, and transfusion-related acute lung injury (TRALI) 5
• Albumin has fewer complications but doesn't replace specific clotting factors 5

Safety Data from Controlled Trials

• Cochrane meta-analysis of 556 Guillain-Barré patients showed plasmapheresis did not increase risk of infection (RR 0.91), blood pressure instability (RR 0.88), cardiac arrhythmias (RR 0.75), or pulmonary embolism (RR 1.01) 1
• However, these studies used 2-6 sessions, fewer than proposed for some conditions like aPAP 1

Special Population Considerations

• Pediatric patients: Plasmapheresis is well-tolerated in children with neurological disease, with complications that can be anticipated and avoided, though procedural risks are higher than in adults 1, 2
• Hemodynamically unstable patients: Require careful benefit-risk assessment given risks of hemodynamic shifts 1, 5

Critical Practice Points

When NOT to Use Plasmapheresis

• Never as monotherapy for antibody-mediated rejection—always combine with immunosuppression 1
• Avoid in dialysis-dependent vasculitis patients without extrarenal manifestations after 3 months of treatment 1
• Not indicated for water-soluble toxins with low protein binding (hemodialysis preferred) 6

Monitoring Requirements

• Continuous observation by highly trained medical personnel is essential for safety 7
• Monitor for hemodynamic changes, coagulation abnormalities, and electrolyte imbalances 2
• Track disease-specific markers (e.g., GM-CSF antibody titers in aPAP, ADAMTS13 in TTP) 1

Prevention Strategies

• Careful selection of replacement fluids based on patient condition and specific disease 5
• Coordinate timing with other immunomodulatory therapies, particularly rituximab 1, 5, 2
• Ensure proper vascular access to minimize catheter-related complications 2

Limitations and Evidence Gaps

• Many indications lack randomized controlled trials, with evidence based on case series and expert opinion 1, 4
• For rare syndromes, randomized trials are not feasible, necessitating multiinstitutional cooperation for larger case series 4
• Mechanisms of action beyond antibody removal (e.g., removal of proinflammatory molecules, complement components) remain incompletely understood 8, 3
• Long-term outcomes data are limited for many indications 1