Lab Tips

Failed crossmatches can be devastating because one failure often affects many potential surgeries. Although some crossmatch failures are unavoidable, the HLA laboratory can prevent most unexpected crossmatch failures by playing a proactive role in donor selection.

The NKR has invested in high-resolution typing and developed tools to preview potential donor matches, which can help avoid unexpected crossmatch failures. This allows for highly accurate virtual crossmatches.

Establish an understanding of your crossmatch results with the transplant team.

1. Convey the importance of avoiding sensitizing events and immediately reporting potential sensitizing events to the transplant team and the laboratory.
   1. Patients should notify the transplant team prior to being transfused, having surgery, etc. Retest patients whose antibody profiles may have changed.
2. Review patients with special requirements for compatibility (e.g., children, patients unable or unwilling to accept a donor with potential incompatibilities).
3. Establish clear crossmatch thresholds with your transplant team.
   1. Borderline positive or negative results may change with retesting.
   2. Flow cytometry results are semi-quantitative, rather than a dichotomous positive or negative, flow values provide an indication of increasing risk.
4. Anticipate confounding crossmatch results.
   1. Screen for IgM or autoantibodies.
   2. Treat patient sera with DTT or EDTA to reduce prozone effects in solid-phase tests.
   3. Test sera at dilution to identify weak antibodies or antibodies at saturation.
   4. Be careful enrolling patients in KPD with non-HLA antibodies that may preclude a transplant.

Personalize the virtual crossmatch to access the most compatible donors.

1. List all DSAs unless the patient has a cPRA > 99.0%.
2. If the patient cPRA is > 99.0%, low level avoids should be dropped to shorten the wait time to find a match, depending on the patient-specific factors.
3. If the patient cPRA is > 99.0%, discuss the option of participating in the Voucher Program so the donor can donate now and the patient can be prioritized.
4. List more low-level avoids for easy-to-match pairs (patient cPRA < 99.0%) since they will have many potential match opportunities.
5. List more low-level avoids for patients who will not tolerate aggressive immunosuppression, plasmapheresis or who otherwise require a completely DSA-free transplant.
6. Look for donors in the pre-select screens with a low or zero eplet mismatch in combination with DSA avoidance.

Use the NKR pre-select screens for difficult-to-match pairs.

1. Review donors in the avoid conflict tab with one avoid conflict.
2. Determine whether desensitization is feasible for specific incompatibilities.
3. Review ABOi donors for 100% cPRA patients (ABOi is often less difficult than desensitization for HLA).

Evaluate patients with allele-specific antibodies.

1. Review the high-resolution typing results provided by the NKR lab to find donors without allele specific antibodies.
2. Use tools like the epitope registry (https://www.epregistry.com.br) to evaluate allele reactivities in the context of shared potential epitopes.

Use exploratory crossmatches for cPRA > 99.0% patients who have:

1. A weak DSA.
2. Multiple low-level DSAs.
3. Cw, DQ or DP DSAs with uncertain crossmatch potential.
4. Allele-specific antibodies not likely to react with a selected donor.

Exploratory XMs for patients with cPRA>99% where the virtual crossmatch is unpredictable should be requested as soon as the potential donor becomes available via pre-select. This crossmatch should be expedited and completed the same day that the cells arrive.