Perioperative Plasmapheresis Protocol for Lung Transplant with PRA 26%
For a lung transplant candidate with PRA 26%, implement intraoperative therapeutic plasma exchange (iTPE) only if there is a positive donor-specific antibody (DSA) crossmatch at the time of transplant, not based on PRA level alone.
Risk Stratification Based on Antibody Profile
A PRA of 26% indicates moderate sensitization, but the critical decision point is whether actual DSAs exist against the specific donor. The evidence demonstrates that:
- PRA alone does not determine need for desensitization - what matters is the presence of complement-fixing DSAs (particularly C1q-fixing antibodies) and their mean fluorescence intensity (MFI) 1
- Patients with C1q-fixing DSAs have nearly tripled risk of allograft loss compared to those without 1
- The highest risk occurs when DSA MFI >7000 or immunodominant C3d ratio ≥4 1
When to Use Intraoperative Plasmapheresis
Proceed with iTPE protocol if:
- Positive flow cytometry crossmatch with identified DSAs
- DSAs are complement-fixing (C1q or C3d positive)
- DSA MFI >5000-7000 range
- No alternative acceptable donor available
Do NOT routinely use iTPE if:
- PRA positive but crossmatch negative
- Only non-complement-fixing antibodies present
- DSA MFI <5000
Recommended Intraoperative Protocol
Based on the Toronto experience with excellent long-term outcomes (median allograft survival 8.4 years in DSA-positive patients), the perioperative protocol should include 2:
Intraoperative components:
- Plasma exchange during transplant procedure
- Intravenous immunoglobulin (IVIG) administration
- Antithymocyte globulin (ATG)
Practical execution:
- Single volume plasma exchange performed intraoperatively
- IVIG 2g/kg divided over 2-4 days post-transplant
- ATG induction per institutional protocol
Critical Bleeding Risk Consideration
Important caveat: iTPE increases perioperative bleeding risk with odds ratio 1.9 for requiring ≥5 units packed red blood cells, but this does not translate to increased hemothorax rates (5% in both groups) or 30-day mortality (3.5% vs 2.1%, p=0.31) 3.
Prepare for:
- Mean 4.2 units pRBC transfusion vs 2.9 without iTPE
- Have blood products readily available
- Consider using fresh frozen plasma as replacement fluid to minimize coagulopathy 4
Post-Transplant Antibody-Mediated Rejection Protocol
If AMR develops post-transplant (distinct from prophylactic perioperative treatment), use standardized protocol 1, 5:
Standard regimen:
- 5 sessions of plasmapheresis every other day
- IVIG with each session
- Rituximab 375 mg/m²
For predicted non-responders (pre-treatment MFI at 1:16 dilution remains high):
- Escalate to 8 plasmapheresis sessions
- Add bortezomib
- This aggressive protocol showed 82.1% response rate 1
Avoid This Common Pitfall
Do not attempt pre-transplant desensitization protocols for broadly sensitized candidates (cPRA ≥80%). Multi-modal pretransplant desensitization with plasmapheresis, bortezomib, and rituximab has been shown to be ineffective at reducing PRA or cPRA in lung transplant candidates 6. The Toronto perioperative approach is superior - accept DSA-positive transplants with intraoperative desensitization rather than attempting to reduce antibodies pre-transplant.
Long-Term Outcomes
The evidence strongly supports that with appropriate perioperative desensitization, DSA-positive lung transplant recipients achieve:
- Comparable allograft survival to unsensitized patients (8.4 vs 5.8 years median) 2
- Similar CLAD-free survival (6.8 vs 5.7 years) 2
- This dramatically expands donor pool for sensitized candidates without compromising outcomes
For your specific patient with PRA 26%: Proceed to transplant evaluation, obtain detailed single antigen bead testing to identify specific unacceptable antigens, and reserve iTPE protocol for when a donor with positive DSA crossmatch is identified.