Is plasmapheresis (plasma exchange) indicated for hemolytic anemia?

Is Plasmapheresis Indicated for Hemolytic Anemia?

Plasmapheresis is NOT routinely indicated for most forms of hemolytic anemia, with the notable exception of symptomatic hyperviscosity from paraproteinemia and select severe, refractory cases of autoimmune hemolytic anemia (AIHA) where it serves only as a temporizing bridge to definitive immunosuppressive therapy. 1

Primary Indication: Hyperviscosity Syndrome

Plasmapheresis is first-line therapy for symptomatic hyperviscosity due to paraproteinemia (such as in Waldenström macroglobulinemia), which can present with hemolytic anemia as part of the clinical syndrome. 2, 1

• The American Society of Hematology designates this as a high-strength recommendation for immediate plasmapheresis when patients present with symptomatic hyperviscosity 1
• In Waldenström macroglobulinemia specifically, plasmapheresis should be used immediately for symptomatic hyperviscosity and can prevent IgM flare before rituximab administration in patients with IgM levels >4000 mg/dL 2
• However, plasmapheresis alone is not effective treatment of the underlying disease and must be followed by rapidly acting cytoreductive treatment 2

Limited Role in Autoimmune Hemolytic Anemia

For typical warm or cold autoimmune hemolytic anemia, plasmapheresis is NOT standard therapy and should only be considered in life-threatening, refractory cases as a temporary bridge until immunosuppressive therapy becomes effective. 3, 4

When to Consider in AIHA:

• Severe, life-threatening hemolysis refractory to conventional therapy with corticosteroids and immunoglobulin 3
• As a temporizing bridge while awaiting response to rituximab or other immunosuppressive agents 3
• The evidence shows plasmapheresis may have more benefit in cold AIHA (with T½ improvement from 7.8 to 20.4 days) compared to warm AIHA (minimal T½ change from 2 to 1.8 days) 5

Critical Limitations:

• Results in AIHA are inconsistent and unpredictable across case reports 4
• The proper role remains uncertain even after decades of sporadic use 4
• Plasmapheresis only temporarily reduces circulating autoantibody levels and must be combined with corticosteroids and immunosuppressive drugs 6
• Rebound antibody production occurs rapidly without concurrent immunosuppression 1

Immune Checkpoint Inhibitor-Related Hemolytic Anemia

For immune checkpoint inhibitor-induced hemolytic anemia, plasmapheresis is NOT mentioned as standard therapy; management focuses on holding the checkpoint inhibitor and using corticosteroids with IVIG. 2

• Hemolytic anemia from checkpoint inhibitors is managed by withholding the drug, corticosteroids, and IVIG 2
• Plasmapheresis is reserved for other severe immune-related adverse events (particularly myasthenia gravis and neurologic toxicities), not hemolytic anemia specifically 2

Practical Protocol When Plasmapheresis Is Used

If plasmapheresis is employed for severe refractory AIHA:

• Perform 5-7 sessions over 10-14 days exchanging 1-1.5 plasma volumes per session 6, 5
• Administer corticosteroids concurrently, not after—steroids are not significantly removed by plasmapheresis due to high protein binding 7
• Give rituximab 48-72 hours after the last plasmapheresis session to avoid drug removal 7
• Administer IVIG only AFTER plasmapheresis is complete, never before, as the procedure will remove the immunoglobulin 7, 8
• Monitor for complications including coagulation defects from clotting factor removal, hemodynamic shifts, infection risk, and thrombosis 1

Common Pitfalls to Avoid

• Do not use plasmapheresis as monotherapy—it must be combined with immunosuppression or the hemolysis will recur 2, 1
• Do not give IVIG before or during plasmapheresis—this wastes expensive therapy as it will be immediately removed 7, 8
• Do not withhold steroids during plasmapheresis thinking they will be removed—this delays necessary immunosuppression 7
• Do not expect consistent benefit in warm AIHA—evidence shows minimal improvement in RBC survival compared to cold AIHA 5, 4

Bottom Line Algorithm

For hemolytic anemia, use plasmapheresis ONLY if:

1. Symptomatic hyperviscosity from paraproteinemia → Immediate plasmapheresis 2, 1
2. Severe, life-threatening AIHA refractory to steroids/IVIG → Consider plasmapheresis as bridge to rituximab 3
3. Cold AIHA with severe hemolysis → May have better response than warm AIHA 5

For all other hemolytic anemias, plasmapheresis is NOT indicated and standard immunosuppressive therapy should be used 2, 4