What are the indications and guidelines for plasmapheresis in clinical practice?

Plasmapheresis in Clinical Practice

Plasmapheresis is a life-saving first-line therapy for thrombotic thrombocytopenic purpura (TTP) and cardiac transplant antibody-mediated rejection, while serving as critical adjunctive therapy for severe ANCA-associated vasculitis with renal failure, Guillain-Barré syndrome requiring ventilation, and immune checkpoint inhibitor-related myasthenia gravis or encephalitis. 1

Mechanism and Technical Fundamentals

Plasmapheresis mechanically removes circulating antibodies, immune complexes, and pathogenic proteins through extracorporeal membrane filtration or centrifugation, with blood reconstituted using albumin, fresh-frozen plasma, or crystalloid before reinfusion. 1 Standard protocols involve exchanging twice the blood volume, with typical courses ranging from 2-6 sessions for neurologic conditions to daily exchanges for 5 days in cardiac rejection. 1

Category I Indications: First-Line Therapy (Do Not Delay)

Thrombotic Thrombocytopenic Purpura

• Continue daily plasma exchange for 14 days or until ADAMTS13 antibodies become undetectable. 1
• Do not delay initiation while awaiting laboratory confirmation when clinical suspicion is high. 2
• In children, deferring plasmapheresis for 24-48 hours until ADAMTS13 results are available may be reasonable due to lower TTP incidence and higher procedural risks. 2

Cardiac Transplant Antibody-Mediated Rejection

• Always combine plasmapheresis with immunosuppression—never use as monotherapy. 1
• In one series of 12 hemodynamically unstable AMR patients treated with plasma exchange plus methylprednisolone, 1-year survival was 75% and 5-year survival was 51%. 1

Category II Indications: Adjunctive Therapy with Strong Evidence

ANCA-Associated Vasculitis with Severe Renal Disease

• Add plasmapheresis for patients requiring dialysis or with rapidly increasing serum creatinine. 3
• Use 60 ml/kg volume replacement, 7-10 treatments total. 3
• The MEPEX trial demonstrated benefit in patients with serum creatinine ≥5.8 mg/dL, though longer-term analyses have raised questions about sustained benefit. 3, 1
• Discontinue cyclophosphamide after 3 months in patients who remain dialysis-dependent without extrarenal manifestations. 3

Diffuse Pulmonary Hemorrhage in ANCA Vasculitis

• Initiate plasmapheresis daily until bleeding stops, then every other day for total of 7-10 treatments. 3
• Although no prospective studies exist, retrospective data indicate improved pulmonary outcomes with high mortality reduction and low procedural risk. 3

Guillain-Barré Syndrome (Grade 3-4)

• Start IVIG (0.4 g/kg/d for 5 days) or plasmapheresis for severe disease with self-care limitation, walking impairment, dysphagia, facial weakness, or respiratory muscle weakness. 3
• Plasmapheresis is particularly effective when initiated within 7 days of onset and for patients requiring mechanical ventilation. 4, 5
• Admit to inpatient unit with ICU-level monitoring capability. 3
• Cochrane meta-analysis of 556 patients showed plasmapheresis did not increase infection, blood pressure instability, cardiac arrhythmias, or pulmonary embolism risk. 1

Immune Checkpoint Inhibitor-Related Myasthenia Gravis (Grade 3-4)

• Permanently discontinue checkpoint inhibitor and initiate IVIG 2 g/kg IV over 5 days or 5-day plasmapheresis course. 3
• Combine with 1-2 mg/kg methylprednisolone daily, weaning based on symptom improvement. 3
• Add pyridostigmine starting at 30 mg orally three times daily, gradually increasing to maximum 120 mg four times daily. 3
• Avoid β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides. 3

Immune Checkpoint Inhibitor-Related Encephalitis

• For severe or progressing symptoms with oligoclonal bands, administer pulse methylprednisolone 1 g IV daily for 3-5 days plus IVIG 2 g/kg over 5 days. 3
• If positive for autoimmune encephalopathy or paraneoplastic antibodies with limited improvement, offer rituximab or plasmapheresis in consultation with neurology. 3

Safety Profile and Complications

Mortality and Serious Adverse Events

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

Common Complications

• Blood pressure instability occurs in 8.4% of procedures due to rapid fluid shifts. 6, 2, 7
• Cardiac arrhythmias occur in 3.5% of procedures. 7
• Coagulation defects from clotting factor removal. 6, 2
• Increased infection risk from immunoglobulin removal. 6, 2
• Rare but serious: pulmonary embolism, transfusion-related acute lung injury (TRALI) with FFP. 6, 2

Replacement Fluid Selection

• FFP carries risks of ABO incompatibility, infectious disease transmission, and allergic reactions. 6
• Albumin has fewer complications but does not replace specific clotting factors. 6
• Double filtration plasmapheresis (DFPP) is more selective at removing antibodies, reducing need for replacement blood products with comparable outcomes to standard plasma exchange. 8

Critical Practice Points and Pitfalls

Drug Timing Considerations

• Administer rituximab after plasmapheresis, as the procedure removes the drug from circulation. 3, 6, 2
• Coordinate timing carefully when combining with other biologic therapies.

Monitoring Requirements

• Track hemodynamic changes, coagulation abnormalities, and electrolyte imbalances throughout treatment. 1, 2
• Monitor disease-specific markers: ADAMTS13 titers in TTP, ANCA titers in vasculitis, antiganglioside antibodies in Guillain-Barré. 1
• Frequent neurochecks and pulmonary function testing (NIF/VC) for neurologic indications. 3

Special Population Considerations

• Plasmapheresis is well-tolerated in children with neurological disease, though procedural risks are higher than in adults. 1
• Careful benefit-risk assessment required in hemodynamically unstable patients. 6

Conditions Where Plasmapheresis Shows Limited Benefit

• Multiple sclerosis: Clinical trials show little to no sustained benefit, with unfavorable cost-benefit ratio. 9
• The assumption that pathologic autoantibodies are accessible in the vascular compartment and that target organs recover rapidly after antibody removal does not hold for all conditions. 9