What are the indications for plasmapheresis?

Indications for Plasmapheresis

Plasmapheresis is indicated as first-line therapy for thrombotic thrombocytopenic purpura (TTP), severe Guillain-Barré syndrome, symptomatic hyperviscosity from paraproteinemia, and cardiac transplant antibody-mediated rejection, while serving as adjunctive therapy for ANCA-associated vasculitis with severe renal disease, myasthenia gravis with significant symptoms, and diffuse pulmonary hemorrhage. 1, 2

Category I: First-Line Therapy (Strongest Indications)

Hematological Emergency

• TTP requires daily plasma exchange as the treatment of choice, continued for 14 days or until ADAMTS13 antibodies become undetectable 2
• Symptomatic hyperviscosity due to paraproteinemia (IgM, IgG, IgA) warrants immediate plasmapheresis 1
• Preventive plasmapheresis before rituximab therapy in patients with IgM ≥4 g/dL prevents symptomatic IgM flares 1

Cardiac Transplantation

• Antibody-mediated rejection in cardiac transplant patients requires plasmapheresis combined with immunosuppression as standard management 2
• In hemodynamically unstable AMR patients treated with plasma exchange plus methylprednisolone, 1-year survival reaches 75% 2
• Typical protocol involves daily exchanges for 5 days 2

Neurological Emergencies

• Severe Guillain-Barré syndrome with self-care limitation, walking impairment, dysphagia, facial weakness, or respiratory muscle weakness requires immediate plasmapheresis or IVIG 2
• Plasmapheresis demonstrates high-strength evidence as first-line therapy 1

Category II: Adjunctive Therapy with Strong Evidence

Renal Conditions

• ANCA-associated vasculitis requiring dialysis or with rapidly increasing serum creatinine (≥5.8 mg/dL) requires plasmapheresis addition to immunosuppression 1, 2
• Protocol: 60 mL/kg volume replacement, 7-10 treatments total 2
• Discontinue cyclophosphamide after 3 months if patient remains dialysis-dependent without extrarenal manifestations 2
• Anti-glomerular basement membrane (anti-GBM) disease benefits from plasmapheresis with moderate-strength evidence 1

Pulmonary Emergencies

• Diffuse pulmonary hemorrhage in ANCA vasculitis requires daily plasmapheresis until bleeding stops, then every other day for 7-10 total treatments 1, 2
• Autoimmune pulmonary alveolar proteinosis (aPAP) refractory to GM-CSF and rituximab may benefit from plasmapheresis, though higher intensity regimens are needed 1

Neurological Conditions (Adjunctive)

• Myasthenia gravis with significant symptoms benefits from plasmapheresis with moderate-strength evidence 1
• Immune checkpoint inhibitor-related myasthenia gravis requires permanent discontinuation of checkpoint inhibitor plus 5-day plasmapheresis course or IVIG, combined with methylprednisolone 1-2 mg/kg daily 2
• Severe immune-mediated neuropathies with rapid progression warrant plasmapheresis 1

Severe Immunotherapy Toxicities

• Immune checkpoint inhibitor-related encephalitis with severe or progressing symptoms and oligoclonal bands requires pulse methylprednisolone 1 g IV daily for 3-5 days plus IVIG 2 g/kg over 5 days 2
• Plasmapheresis is recommended for severe neurologic adverse events from immunotherapy 1

Category III: Refractory Autoimmune Conditions

Dermatological

• Refractory pemphigus vulgaris unresponsive to corticosteroids and immunosuppressants may benefit from plasmapheresis (not recommended for newly diagnosed cases) 1

Other Conditions

• Severe cryoglobulinemia with acute kidney involvement 1
• Certain intoxications with high plasma protein binding (phalloid mushroom, tricyclic antidepressants, L-thyroxine, verapamil, diltiazem) 3

Critical Technical Considerations

Procedure Protocols

• Standard plasma exchange involves exchanging twice the blood volume 2
• Typical courses: 2-6 sessions for neurologic conditions, 5-7 days for cardiac AMR, 7-10 treatments for vasculitis 1, 2
• Replace with albumin, fresh-frozen plasma, or crystalloid solutions 1

Timing with Other Therapies

• Always administer rituximab AFTER plasmapheresis, as the procedure removes the drug from circulation 1, 2
• Never use plasmapheresis as monotherapy for antibody-mediated conditions—always combine with immunosuppression to prevent rebound antibody production 1, 2

Safety Profile and Complications

Mortality and Major Risks

• Overall mortality: 0.05% based on systematic reviews of >15,500 patients 1, 2, 4
• Severe life-threatening episodes (shock, persistent arrhythmias, hemolysis) occur in 2.16% of procedures 5

Common Complications

• Hypotension occurs in 8.4% of procedures 5
• Cardiac arrhythmias in 3.5% 5
• Hemodynamic shifts, increased infection risk, and thrombosis 1, 4
• Removal of clotting factors can cause coagulation defects 1, 4
• When combined with immunosuppressants, increased risk of opportunistic infections requiring prophylaxis 1

Monitoring Requirements

• Track hemodynamic changes, coagulation abnormalities, and electrolyte imbalances 2
• Monitor disease-specific markers (GM-CSF antibody titers in aPAP, ADAMTS13 in TTP) 2