In critically ill ICU patients, what are the indications for initiating plasmapheresis, the recommended exchange regimen, monitoring parameters, potential complications, and alternative therapies?

Plasmapheresis in the ICU: A Comprehensive Clinical Guide

Primary Indications for Plasmapheresis in Critical Care

Plasmapheresis (therapeutic plasma exchange, TPE) should be initiated in ICU patients primarily for ANCA-associated vasculitis with severe renal involvement or pulmonary hemorrhage, thrombotic thrombocytopenic purpura (TTP), and anti-GBM disease, where it directly impacts mortality and morbidity. 1

Category I Indications (Strong Evidence)

ANCA-Associated Vasculitis:

• Initiate plasmapheresis immediately for patients requiring dialysis or with rapidly increasing serum creatinine (KDIGO recommendation 1C) 1
• Add plasmapheresis for diffuse pulmonary hemorrhage (KDIGO recommendation 2C) 1
• Use in overlap syndrome of ANCA vasculitis and anti-GBM glomerulonephritis (KDIGO recommendation 2D) 1

Thrombotic Microangiopathies:

• TTP represents the most urgent indication, where plasmapheresis is life-saving and should be initiated within hours of clinical suspicion 1, 2
• Pathogen-inactivated FFP is preferred as replacement fluid for TTP 1

Category II Indications (Moderate Evidence)

Neurologic Emergencies:

• Guillain-Barré syndrome with rapid progression or respiratory failure 2, 3, 4
• Myasthenia gravis crisis unresponsive to medical therapy 3, 4
• Acute inflammatory demyelinating polyneuropathy 3

Hematologic Disorders:

• Hyperviscosity syndrome (Waldenström macroglobulinemia, multiple myeloma) 3, 4
• Severe hemolytic disease of the newborn 3

Recommended Exchange Regimen

Standard Protocol Parameters

Volume and Frequency:

• Exchange volume: 60 ml/kg body weight per treatment (approximately 1-1.5 plasma volumes) 1
• For ANCA vasculitis with diffuse pulmonary hemorrhage: 7-10 treatments over 14 days—daily until bleeding stops, then every other day 1
• For TTP: daily exchanges until platelet count normalizes and LDH improves, typically 5-7 days minimum 2, 4

Replacement Fluid Selection:

• Use fresh frozen plasma (FFP) at 60 ml/kg for TTP and conditions requiring coagulation factor replacement 1
• Use 5% albumin for most other indications to minimize infectious and allergic risks 5, 4
• Ensure ABO-compatible FFP; use group AB if blood type unknown 1, 6

Technical Approach:

• Centrifugal or membrane filtration methods are both acceptable 4
• Maintain adequate vascular access (large-bore central venous catheter, typically 12-14 French) 5, 4
• Use citrate anticoagulation in most cases 5, 4

Critical Monitoring Parameters

Pre-Procedure Assessment

• Baseline coagulation studies (PT/INR, aPTT, fibrinogen) 5, 4
• Complete blood count with platelet count 5
• Serum calcium, magnesium, and potassium 5, 4
• Hemodynamic stability assessment (blood pressure, heart rate) 5

Intra-Procedure Monitoring

• Continuous vital signs every 15-30 minutes 5, 4
• Ionized calcium levels if symptomatic hypocalcemia develops (citrate toxicity) 5, 4
• Volume status and hemodynamic parameters to prevent hypotension 5
• Circuit pressures and flow rates to detect technical complications 4

Post-Procedure Monitoring

• Coagulation parameters after each session, especially if FFP used 5
• Platelet count (expect 10-20% decrease per session) 5, 4
• Fibrinogen levels (FFP contains only ~2g per 4 units, may require cryoprecipitate supplementation) 1, 7
• Immunoglobulin levels if prolonged therapy (consider IVIG replacement) 5
• Drug levels for medications with high protein binding (adjust dosing accordingly) 5

Potential Complications and Management

Immediate Life-Threatening Complications

Hypotension (Most Common):

• Occurs in 5-25% of procedures due to rapid fluid shifts 5, 4
• Management: Slow exchange rate, administer crystalloid boluses, consider albumin priming of circuit 5

Citrate Toxicity:

• Presents as perioral numbness, paresthesias, tetany, or cardiac arrhythmias 5, 4
• Management: Reduce citrate infusion rate, administer calcium gluconate 10 ml IV (10% solution) 5
• Monitor ionized calcium; maintain >1.0 mmol/L 5

Transfusion-Related Acute Lung Injury (TRALI):

• Risk increases with FFP use, particularly from male donors 1, 7
• Prevention: Use male-only or nulliparous female donor plasma 1
• Management: Supportive care, mechanical ventilation if needed 1, 7

Moderate-Risk Complications

Coagulopathy:

• Removal of clotting factors, especially with albumin replacement 5, 4
• Management: Monitor fibrinogen; transfuse cryoprecipitate if <1.0-1.5 g/L 1, 7
• Consider FFP replacement if active bleeding and INR >1.5 1, 7

Thrombocytopenia:

• Expected 10-20% platelet loss per exchange 5, 4
• Management: Transfuse platelets if count <20-50 × 10⁹/L with bleeding risk 1

Infection:

• Central line-associated bloodstream infections 5, 4
• Prevention: Strict aseptic technique, daily line assessment 5

Allergic Reactions:

• Range from urticaria to anaphylaxis, more common with FFP 1, 5
• Management: Antihistamines for mild reactions; epinephrine for anaphylaxis 5

Metabolic Complications

Electrolyte Disturbances:

• Hypocalcemia, hypomagnesemia, hypokalemia from citrate chelation 5, 4
• Management: Routine supplementation; calcium gluconate 1-2g IV, magnesium sulfate 2g IV as needed 5

Hypothermia:

• From rapid infusion of cold replacement fluids 5
• Prevention: Warm replacement fluids to body temperature 5

Alternative and Adjunctive Therapies

When to Consider Alternatives

Immunoadsorption Plasmapheresis (IAPP):

• More selective removal of pathogenic antibodies without replacement fluid requirement 8
• Advantages: No FFP-related complications, preserves beneficial plasma proteins 8
• Limitations: Limited availability, specific column requirements 8

Double Filtration Plasmapheresis (DFPP):

• Semi-selective removal based on molecular weight 8
• Requires less replacement fluid than conventional TPE 8

Adjunctive Immunosuppression

For ANCA Vasculitis:

• Cyclophosphamide plus corticosteroids as initial treatment (KDIGO 1A recommendation) 1
• Alternative: Rituximab plus corticosteroids for patients without severe disease or CYC contraindications (KDIGO 1B recommendation) 1
• Plasmapheresis is adjunctive, not monotherapy 1

Maintenance Therapy:

• Continue for at least 18 months after remission (KDIGO 2D recommendation) 1
• Discontinue CYC after 3 months if dialysis-dependent without extrarenal manifestations (KDIGO 2C recommendation) 1

Critical Pitfalls to Avoid

Common Clinical Errors

1. Delaying Plasmapheresis in TTP:

• TTP is a medical emergency; mortality approaches 90% without treatment 2
• Do not wait for ADAMTS13 results—initiate TPE on clinical suspicion alone 2, 4

2. Using Plasmapheresis for Inappropriate Indications:

• Avoid in sepsis, ARDS, or multi-organ dysfunction syndrome where evidence remains experimental 3
• Not indicated for routine coagulopathy correction in liver failure 7

3. Inadequate Vascular Access:

• Small-bore catheters cause hemolysis and inadequate flow rates 5, 4
• Use dedicated large-bore dialysis catheters (12-14 French minimum) 5

4. Failure to Replace Medications:

• Plasmapheresis removes protein-bound drugs (antibiotics, anticonvulsants, immunosuppressants) 5
• Redose medications after each session, particularly antimicrobials and immunosuppressants 5

5. Ignoring Citrate Toxicity Symptoms:

• Perioral tingling is an early warning sign requiring immediate intervention 5
• Prophylactic calcium supplementation in high-risk patients (liver disease, massive transfusion) 5

Contraindications and Cautions

Absolute Contraindications:

• Hemodynamic instability unresponsive to vasopressors 5, 4
• Active uncontrolled bleeding without ability to correct coagulopathy 5

Relative Contraindications:

• Severe thrombocytopenia (<20 × 10⁹/L) without platelet support 5
• Recent surgery or invasive procedures (within 24-48 hours) 5
• Inability to achieve adequate vascular access 5, 4

Special Considerations in Massive Hemorrhage

High-Ratio Transfusion Context:

• In trauma patients with massive bleeding, use high-ratio transfusion strategies (1:1:1 FFP:platelets:RBC) rather than plasmapheresis 1, 9
• Plasmapheresis removes coagulation factors and would worsen coagulopathy in acute hemorrhage 1
• FFP therapeutic dose is 10-15 ml/kg for coagulopathy correction, not removal 1, 7, 6