What are the potential complications and management strategies for patients undergoing plasma exchange?

Complications During Plasma Exchange

Plasma exchange carries a 25-43% overall complication rate, but severe life-threatening events occur in less than 1% of procedures, with the most common complications being hypotension (3.6-15%), citrate-induced hypocalcemia (19.6%), and mild allergic reactions (3%), all of which are manageable with appropriate monitoring and protocol adjustments. 1, 2, 3

Primary Complications and Their Frequencies

Hemodynamic Complications

• Hypotension is the most significant hemodynamic complication, occurring in 3.6-15.2% of procedures, and results from large volume shifts as 1-1.5 plasma volumes are removed and replaced over 2-3 hours 1, 4, 3
• Hypotension is asymptomatic in 95.8% of cases but requires continuous blood pressure monitoring throughout the procedure 3
• Patients with hypertrophic obstructive cardiomyopathy (HOCM) face particularly high risk because hypotension worsens left ventricular outflow tract obstruction 1
• Cardiac arrhythmias and myocardial infarction are rare but documented severe complications 4

Metabolic and Electrolyte Disturbances

• Citrate toxicity causing hypocalcemia occurs in 7.8-19.6% of procedures and presents with paraesthesias, muscle cramps, or more severe symptoms 4, 3
• Citrate metabolism is dramatically impaired by hypoperfusion, hypothermia, and hepatic insufficiency, increasing risk 5
• Metabolic alkalosis can develop with repeated fresh frozen plasma (FFP) use 6

Allergic and Transfusion Reactions

• Allergic reactions occur in 3% of sessions, exclusively when FFP is used as replacement fluid 3
• Severe allergic reactions causing life-threatening events occur in 0.5% of procedures 2
• Transfusion-related acute lung injury (TRALI) is a severe adverse effect associated with leucocyte antibodies in transfused plasma 5

Infectious Complications

• Catheter-related bacteremia and sepsis occur in 0.3% of procedures, particularly with permanent vascular access (shunts or catheters) 2, 6
• All patients receiving only FFP as replacement developed non-A, non-B hepatitis in one series, though pathogen-inactivated plasma minimizes this risk 5, 6

Coagulation Disorders

• Removal of clotting factors creates bleeding risk, though hemorrhagic episodes are uncommon when proper protocols are followed 1, 7, 6
• Patients with underlying hematologic disorders have higher bleeding diathesis risk than neurological patients 4

Other Complications

• Visual scotomata occur in 1.3% of procedures 4
• Gross hemolysis is rare but documented 4
• Acute anemia, vasovagal reactions, and abdominal pain occur in the mild complication category (18% total incidence) 6

Risk Stratification by Patient Population

High-Risk Populations

• Neurological patients have significantly higher complication rates (P=0.013) compared to internal medicine patients, primarily due to higher rates of hypotension and vascular access complications 2
• Patients with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) have the highest complication risk among internal medicine patients 2
• Patients with renal insufficiency face higher severe infection risk 4
• Patients requiring concurrent cardiovascular surgery face compounded procedural risks 1

Management Strategies to Prevent and Treat Complications

Hemodynamic Monitoring and Support

• Maintain continuous hemodynamic monitoring throughout the procedure, including blood pressure, heart rate, and clinical assessment 1
• Ensure adequate volume status before initiating plasma exchange to prevent hypotension that compromises organ perfusion 1
• For HOCM patients specifically: use intravenous phenylephrine (pure vasoconstrictor) rather than inotropic agents (dopamine, dobutamine, norepinephrine) which worsen left ventricular outflow tract obstruction 1
• Avoid vasodilators including dihydropyridine calcium channel blockers, ACE inhibitors, and ARBs in HOCM patients 1

Medication Management

• Continue beta-blocker therapy throughout plasma exchange in HOCM patients to maintain heart rate control and reduce outflow tract obstruction 1
• If beta-blockers are contraindicated in HOCM, use verapamil cautiously, particularly in patients with high gradients or advanced heart failure 1
• Administer cyclophosphamide after plasma exchange sessions to avoid removal 1
• Hold plasma exchange for 48-72 hours post-rituximab infusion to prevent drug removal 1

Replacement Fluid Selection

• Use albumin rather than FFP when possible to minimize transfusion reactions, reduce hemodynamic fluctuations, and decrease hypocalcemia risk 1, 3
• Albumin use is associated with higher hypotension rates (19.8% vs 8.9%) but lower hypocalcemia (11.7% vs 28%) and eliminates allergic reactions compared to FFP 3
• Reserve FFP exclusively for thrombotic microangiopathies or when bleeding risk exists, as it is highly allergenic and expensive 8

Citrate Management

• Use citrate for anticoagulation as it is the preferred method 8
• Monitor for citrate toxicity symptoms (paraesthesias, muscle cramps) and treat hypocalcemia promptly 4, 3
• Exercise particular caution in patients with hepatic insufficiency, hypothermia, or hypoperfusion states 5

Infection Prevention

• Use meticulous technique with vascular access to prevent catheter-related infections 6
• Consider avoiding permanent vascular access when possible, as shunts and catheters increase sepsis risk 6
• Use pathogen-inactivated plasma when FFP is necessary to minimize infectious disease transmission 5

Procedure-Specific Parameters

• Exchange 1-1.5 plasma volumes per session (estimated at 40 mL/kg body weight) 8
• Typical protocols involve 5-10 sessions over 10-14 days for neurological conditions 9
• Perform sessions on alternate days or every other day 7

Critical Pitfalls to Avoid

• Do not delay treatment beyond 2 weeks of symptom onset when plasma exchange is indicated, as this is associated with worse neurological outcomes 9
• Do not use MS-directed therapies (interferon-beta, natalizumab) in patients with MOG-IgG antibodies or NMOSD, as these worsen outcomes 7
• Do not underestimate infection risk in patients receiving concurrent immunosuppressive therapy, as serious infection risk increases (risk ratio 1.19) 5
• Do not use plasma exchange routinely for all patients with active glomerulonephritis; reserve for high-risk patients (creatinine ≥5.8 mg/dL) who accept increased infection risk, as the benefit-harm balance is unfavorable in low-risk patients 5

Overall Safety Profile

• Severe, life-threatening adverse events occur in only 0.3-0.7% of procedures 2, 3
• Most complications (13.7%) are mild and self-limited 2
• Moderate complications occur in 11% of procedures 2
• When performed by trained teams with appropriate monitoring, plasma exchange is a safe therapy with manageable risks 3