When is therapeutic plasma exchange indicated, how should it be performed and monitored, and what are its contraindications and alternative therapies?

Therapeutic Plasma Exchange: Indications, Performance, and Monitoring

Primary Indications for Plasma Exchange

Plasma exchange should be initiated immediately in anti-GBM disease when suspected, even before diagnostic confirmation, combined with high-dose corticosteroids and cyclophosphamide. 1

Anti-GBM Disease (Strongest Indication)

• Start empirical solumedrol and plasma exchange immediately when anti-GBM disease is suspected to rapidly remove pathogenic antibodies and enhance renal survival 1
• Continue plasma exchange until anti-GBM titers are undetectable on 2 consecutive tests (typically 8 weeks) 1
• Use albumin replacement for standard cases; switch to fresh frozen plasma if alveolar hemorrhage present or recent kidney biopsy performed 1
• Patients with serum creatinine >500 μmol/L (5.7 mg/dL) who do not require dialysis within 72 hours benefit from treatment 1
• Even dialysis-dependent patients should receive treatment if presentation is acute, nonoliguric, with <50% glomerulosclerosis, <100% crescents, and features of acute tubular injury 1

ANCA-Associated Vasculitis (Conditional Indication)

Plasma exchange may be considered for ANCA vasculitis patients with serum creatinine >300 μmol/L (3.4 mg/dL) due to active glomerulonephritis, but should NOT be used routinely for all patients with glomerulonephritis. 1

• Reserve for patients at highest risk of progression to end-stage renal disease 1
• Combined trial data shows decreased ESRD risk (hazard ratio 0.72) but increased infection risk (risk ratio 1.19) 1
• Do NOT use plasma exchange routinely for alveolar hemorrhage in ANCA vasculitis - no mortality or remission benefit demonstrated 1
• Consider only as salvage therapy for critically ill patients not responding to standard immunosuppression 1
• Older guidelines (2009) recommended plasma exchange for serum creatinine >500 μmol/L (5.65 mg/dL), but newer evidence (2021-2024) is more restrictive 1

Neurological Disorders

• First-line therapy for severe Guillain-Barré syndrome with 4-6 sessions over 10-14 days 2
• Myasthenia gravis with significant symptoms 2
• Severe immune-mediated neuropathies with rapid progression 2

Hematological Disorders

• First-line therapy for symptomatic hyperviscosity due to paraproteinemia 2
• Thrombotic thrombocytopenic purpura: exchange 1-1.5 plasma volumes daily until platelet count >150 × 10⁹/L and LDH normalizes 3, 4
• Preventive treatment before rituximab in patients with IgM ≥4 g/dL 2

How to Perform Plasma Exchange

Technical Specifications

• Exchange volume: 1-1.5 plasma volumes (approximately 40 mL/kg body weight) per session 3, 4
• Frequency: Daily sessions initially, then taper based on clinical response 1, 3
• Duration: 5-7 sessions over 10-14 days for most conditions 2, 5
• Replacement fluid: Albumin for standard cases; fresh frozen plasma for bleeding risk, recent biopsy, or alveolar hemorrhage 1, 2

Critical Timing with Concurrent Medications

Corticosteroids should be administered concurrently with plasma exchange, NOT after, as they are not significantly removed by the procedure. 5

• High-dose pulse methylprednisolone (1g daily for 3-5 days) or oral prednisolone (0.5-1 mg/kg/day, maximum 60-80 mg) given during plasma exchange sessions 5
• IVIG must be given AFTER plasma exchange is complete - never before, as it will be removed 2, 5
• Rituximab should be administered 48-72 hours after the last plasma exchange session to avoid drug removal 2, 5
• Cyclophosphamide infusions given immediately after individual plasma exchange sessions 5

Monitoring Parameters

During Treatment

• Anti-GBM antibody titers: Check every 1-2 weeks; continue plasma exchange until negative on 2 consecutive tests 1
• Platelet count and LDH (for TTP): Daily until normalization 3, 4
• Serum creatinine and urine output: Daily assessment of renal function 1
• Fibrinogen levels: Replace with fibrinogen concentrate (3-4g or 50 mg/kg) or cryoprecipitate (15-20 units) if <1.5 g/L, especially with bleeding risk or planned procedures 2
• Hemodynamic parameters: Monitor for hypotension during sessions 6

Kidney Biopsy Prognostic Features

• Degree of acute tubular necrosis 1
• Percentage of crescents (treatment futile if 100% crescents) 1
• Percent tubular atrophy/interstitial fibrosis (avoid if >50%) 1
• Glomerulosclerosis percentage 1

Contraindications and Precautions

Relative Contraindications

• Dialysis-dependent patients with chronic features: >90% remain on dialysis at 1 year; mortality 35% 1
• Oliguric presentation with >50% glomerulosclerosis, >50% tubular atrophy/interstitial fibrosis, or 100% crescents 1
• Inability to tolerate aggressive immunosuppression due to age, frailty, or high infection risk 1

Complications and Risk Management

• Infection risk increases when combined with immunosuppressants - requires prophylactic measures 2, 5
• Pneumocystis prophylaxis with trimethoprim-sulfamethoxazole until cyclophosphamide complete and prednisone <20 mg daily 1
• Coagulation defects from removal of clotting factors 2
• Hemodynamic shifts, thrombosis risk 2
• Procedure-related mortality: 0.05% 2
• Common complications: muscle cramps (6.4%), allergic reactions (4.5%), hypotension (3.6%) 6

Alternative Therapies

For Anti-GBM Disease

• Imlifidase (IgG-degrading enzyme): Single dose with plasma exchange and corticosteroids resulted in 67% dialysis-free survival at 6 months 1
• Rituximab or mycophenolate mofetil for refractory cases 1

For ANCA Vasculitis

• Avacopan with rituximab or cyclophosphamide as glucocorticoid-sparing strategy 1
• Standard immunosuppression (rituximab or cyclophosphamide with glucocorticoids) without plasma exchange for lower-risk patients 1

For TTP

• Twice-daily plasma exchange if poor initial response 4
• Glucocorticoids, antiplatelet agents, rituximab, or splenectomy as adjunctive measures 4

Common Pitfalls to Avoid

1. Do not withhold steroids during plasma exchange thinking they will be removed - this delays necessary immunosuppression 5
2. Do not give IVIG before or during plasma exchange - wastes expensive therapy as it will be removed 2, 5
3. Do not use plasma exchange routinely for ANCA vasculitis with alveolar hemorrhage - no proven benefit and increased infection risk 1
4. Do not continue aggressive treatment in dialysis-dependent patients with chronic biopsy features - poor outcomes with high mortality 1
5. Do not forget maintenance immunosuppression for double-positive (ANCA + anti-GBM) patients - treat as ANCA vasculitis with maintenance therapy 1