Does plasmapheresis remove Intravenous Immunoglobulin (IVIG) from the circulation?

Does Plasmapheresis Remove IVIG?

Yes, plasmapheresis removes IVIG from the circulation because plasma exchange nonselectively removes all proteins, including immunoglobulins, which is why IVIG must always be administered after plasmapheresis is completed, never before or during the procedure. 1, 2

Mechanism of Removal

• Plasmapheresis nonselectively removes all plasma proteins, including immunoglobulins (IgG, IgM, IgA), through extracorporeal separation of plasma from cellular blood components via membrane filtration or centrifugation 1

• Immunoadsorption plasmapheresis is specifically designed to remove only immunoglobulins, making it even more efficient at removing IVIG, though this modality is less widely available 1

• The removed plasma is replaced with albumin, fresh-frozen plasma, or crystalloid, meaning any previously administered IVIG is discarded with the removed plasma 1, 3

Critical Timing Protocols

When to Administer IVIG Relative to Plasmapheresis

• Administer IVIG only after plasmapheresis is complete - giving it before or during the procedure wastes expensive therapy as it will be immediately removed 2, 4, 3

• The standard protocol is to give IVIG 2 g/kg divided into doses after the final plasmapheresis session, typically administered over 2 consecutive days 1

• One Iranian study demonstrated treatment failure when high doses of IVIG were given after each daily plasmapheresis session - the authors suggested reducing to 100 mg/kg replacement doses after each session, then completing the full 2 g/kg cumulative dose after plasmapheresis is finished 5

When to Administer Other Biologics

• Rituximab should be administered 48-72 hours after the last plasmapheresis session to avoid drug removal, as the procedure removes this monoclonal antibody from circulation 2, 4, 3

• Corticosteroids can be administered concurrently with plasmapheresis because they are highly protein-bound and not significantly removed by the procedure 4

Clinical Protocols Demonstrating This Principle

Cardiac Transplant AMR Treatment

• Multiple centers use sequential plasmapheresis followed by IVIG: Stanford protocol specifies plasmapheresis daily or every other day for minimum 5 sessions, with IVIG 2 g/kg divided over days 1-2 and days 29-30 (after plasmapheresis completion) 1

• Cedars-Sinai protocol administers IVIG 2 g/kg on days 1 and 30, with the first day specifically noted as "after completion of rATG" to avoid removal 1

Neurologic Immune-Related Adverse Events

• For immune checkpoint inhibitor-related myasthenia gravis or encephalitis, guidelines recommend either IVIG or plasmapheresis, not both simultaneously, recognizing they work through opposite mechanisms (adding vs. removing immunoglobulins) 1, 2

• When both are needed, the protocol is methylprednisolone pulse dosing first, then consider IVIG or plasmapheresis if no improvement after 3 days - the word "consider" implies choosing one or the other, not combining 1

Renal Transplant AMR

• A 2004 study of 9 patients with acute humoral rejection used plasmapheresis followed by IVIg infusion, achieving mean 1-year serum creatinine of 1.8 mg/dL with only one graft loss 6

Common Pitfalls to Avoid

• Do not give IVIG before plasmapheresis - this wastes the expensive immunoglobulin therapy (IVIG costs >$20,000 per course) as it will be immediately removed 2, 4

• Do not schedule plasmapheresis immediately after IVIG administration - wait at least 48-72 hours if plasmapheresis becomes urgently needed after IVIG has been given 2, 4

• Do not assume small "replacement doses" of IVIG after each plasmapheresis session are sufficient - the full therapeutic dose of 2 g/kg should be completed after plasmapheresis is finished 5

• Do not administer rituximab immediately before or during a plasmapheresis course - this monoclonal antibody will also be removed, wasting therapy 2, 3

Practical Implications for Treatment Sequencing

When treating conditions requiring both plasmapheresis and IVIG (such as cardiac transplant AMR, renal transplant AMR, or severe immune-mediated rejection):

1. Initiate plasmapheresis first (typically 4-7 sessions over 7-14 days) 1, 2

2. Complete the full plasmapheresis course before administering therapeutic IVIG 2, 4, 5

3. Administer IVIG 2 g/kg divided over 2 days after the final plasmapheresis session 1, 6

4. If additional plasmapheresis becomes necessary after IVIG, recognize that the IVIG will be removed and may need to be re-dosed 5

5. Administer rituximab 48-72 hours after the last plasmapheresis if this agent is part of the treatment protocol 2, 4