Is plasma exchange (PE) a recommended treatment for sickle cell crisis?

Plasma Exchange for Sickle Cell Crisis

Plasma exchange (PE) alone is NOT a recommended or standard treatment for sickle cell crisis—red blood cell exchange (RCE) is the established therapeutic apheresis modality for severe acute complications. However, emerging evidence suggests PE may have a role as an adjunctive therapy in refractory cases with multiorgan failure that do not respond to RCE alone.

Standard Approach: Red Blood Cell Exchange, Not Plasma Exchange

• Automated or manual RCE is the recommended apheresis intervention for severe acute chest syndrome (ACS), not plasma exchange 1
• The American Society of Hematology 2020 guidelines suggest RCE over simple transfusion for severe ACS, defined by rapidly falling hemoglobin, severe hypoxia, and/or requirement for invasive respiratory support 1
• RCE rapidly reduces HbS percentage while avoiding hyperviscosity and iron overload that occurs with simple transfusion 1
• For typical vaso-occlusive crises without life-threatening complications, neither RCE nor PE is indicated—management consists of hydration, oxygenation, and analgesia 2, 3

The Rationale Behind Plasma Exchange (Why It's Being Explored)

The theoretical basis for PE in sickle cell disease recognizes that:

• Plasma in SCD patients contains elevated proinflammatory cytokines, adhesion molecules, and prothrombotic factors that promote further sickling and cause direct tissue toxicity 4, 5
• These inflammatory mediators remain elevated even after RCE successfully reduces HbS levels 5
• RCE addresses the red blood cell component but does not remove harmful plasma constituents 4, 6

When Plasma Exchange May Be Considered (Adjunctive Role Only)

PE should only be considered as an adjunct to RCE in critically ill patients with multiorgan failure who are not responding to standard RCE therapy 6. This is based on case series evidence, not randomized trials.

Specific Clinical Scenarios from Case Reports:

• Refractory severe ACS: Patient with persistent severe hypoxia and pain despite adequate RCE who showed rapid clinical improvement after adding PE 4
• Multiorgan failure unresponsive to RCE: Case series of 7 patients with progressive organ failure despite RCE showed improvement in hemolysis markers and organ function within average 15.6 hours after PE, with 6 of 7 surviving 6
• Intractable pain with impending ACS: Patients with severe pain not controlled by RCE alone who achieved rapid pain resolution with PE 4

Important Caveats About This Evidence:

• This represents very low-quality evidence—only case reports and small case series exist 4, 6
• No randomized controlled trials have evaluated PE for sickle cell crisis 1
• The American Society of Hematology guidelines do not mention PE as a treatment option for acute complications 1
• PE should never replace RCE as the primary apheresis modality 6

Practical Implementation If PE Is Considered

If the multidisciplinary team decides to add PE for refractory multiorgan failure:

• Continue RCE as the primary intervention—PE is only adjunctive 6
• Consultation with hematology and transfusion medicine specialists is essential 1
• PE was well-tolerated with no adverse events in reported case series 4
• Monitor for rapid improvement in pain scores, oxygenation, and organ function markers 6
• Typical response time in survivors was approximately 15-16 hours after first PE treatment 6

Critical Pitfalls to Avoid

• Never use PE as first-line therapy for any acute sickle cell complication—RCE is the established standard 1, 6
• Do not delay RCE while considering PE—RCE should be initiated immediately for severe complications 1
• Simple transfusion should be provided if hemoglobin is below 9 g/dL while waiting for RCE availability 1
• Ensure specialized equipment and trained personnel are available before attempting either RCE or PE 1
• In highly alloimmunized patients, identifying sufficient compatible units may preclude RCE altogether 1

Research Gaps and Future Directions

• The American Society of Hematology identifies the need for prospective, controlled trials comparing different therapeutic approaches for severe complications 1
• Current evidence for PE is insufficient to make it a standard recommendation—it remains an experimental adjunct 4, 6
• Development of validated severity scores for ACS and other complications would help identify which patients might benefit from escalated therapies 1