Require Notification of Human Leukocyte Antigen (HLA) Typing Changes At a glance Current policy Histocompatibility laboratories test compatibility of transplant candidate and organ donor tissues using the human leukocyte antigen (HLA) complex. This process is also known as HLA typing. When a candidate is more compatible with the donor, there is less risk the candidate’s body will reject the transplant. There is no current requirement to communicate HLA typing changes to transplant programs or Organ Procurement Organizations (OPOs). Patient safety is at risk when transplant programs are not aware of HLA typing changes. Supporting media Presentation View presentation slides Proposed changes Require notifications when there is a critical change to candidate, recipient, or donor HLA typing. Histocompatibility labs must notify the OPO within one hour of determining the correct typing for a donor and provide documentation of the corrected typing. After receiving the correct documentation from the histocompatibility lab, the OPO will be required to notify all accepting transplant programs and provide documentation within 12 hours. If the discrepancy is discovered before organ recovery, the OPO will be required to notify accepting transplant programs. If a histocompatibility lab becomes aware of a discrepancy in a candidate or recipient’s HLA typing, they will notify the transplant program within five days of determining the correct typing and provide documentation of the corrected typing. Anticipated impact What it's expected to do Improve patient safety by requiring notification when there is a critical change in a donor, candidate or recipient’s HLA. What it won't do Change required HLA testing Themes Patient safety Communication among histocompatibility labs, transplant programs, and OPOs Terms to know Donor Histocompatibility Form: The form submitted by the histocompatibility laboratory containing HLA information of a deceased donor or living donor. Histocompatibility: The examination of HLA in a patient, often referred to as "tissue typing" or "genetic matching." Tissue typing is routinely performed for all donors and transplant candidates to help match the donor with the most suitable recipients to help decrease the likelihood of rejecting the transplanted organ. Human leukocyte antigen (HLA) complex: a group of proteins that helps the immune system distinguish the body's own cells from foreign invaders such as viruses and bacteria. Organ Procurement Organization: An organization responsible for the recovery of organs for transplantation and the promotion of organ donation. OPOs serve as the vital link between the donor and recipient and are responsible for the identification of donors, and the retrieval, preservation and transportation of organs for transplantation. Transplant program: A component within a transplant hospital that provides transplantation of a particular type of organ Click here to search the OPTN glossary Comments American Society for Histocompatibility and Immunogenetics | 03/23/2021 ASHI values the opportunity to comment on this proposal. This is an important policy to improve communication between HLA laboratories, OPO’s and transplant programs and ASHI strongly supports this policy. If logistically feasible ASHI would support another match run as an individual may have missed an opportunity to be matched and alternatively, a proposed recipient may no longer be compatible. The feasibility of performing another match run will depend upon the timepoint in the procurement and allocation process that notification of a typing change occurs. Developing policies around the different scenarios may help guide this process. We also suggest a second minor addition that “Critical HLA Discrepancy” be sent to both the OPO and originating HLA Lab within 1 hour. This will immediately engage all parties and expedite the resolution of the HLA typing discrepancy. Region 10 | 03/23/2021 Region 10 sentiment: 1 Strongly Support, 12 Support, 5 Neutral/Abstain, 0 Oppose, 0 Strongly Oppose. No comments. Region 2 | 03/23/2021 Region 2 sentiment: 5 Strongly Support, 12 Support, 2 Neutral/Abstain, 0 Oppose, 0 Strongly Oppose. No comments. Region 9 | 03/23/2021 Region 9 sentiment: 2 strongly support, 5 support, 1 neutral/abstain, 0 oppose, 0 strongly oppose. No comments. Association of Organ Procurement Organizations | 03/23/2021 The Association of Organ Procurement Organizations (AOPO) recognizes the importance of timely notifications when there is a critical change to candidate, recipient, or donor HLA typing. We support the Histocompatibility Committee’s efforts to modify and update this policy. We do not believe policy should mandate re-execution of the match run in all circumstances but recommend the committee align, where possible, their proposal with existing policies 5.5 Re-Execution of the Match Run Due to New Information and 5.9 Released Organs. We believe automated notifications are an important aspect and should be included as a part of the implementation efforts. AOPO fully supports the committee in this policy change. American Society of Transplant Surgeons | 03/23/2021 The American Society of Transplant Surgeons (ASTS) supports this proposal with the following recommendations. We thank the OPTN Histocompatibility Committee for their work on this proposal and offer the following feedback to their questions. Should an automated electronic notification be included as part of this implementation? Yes. It is important to notify the accepting center as soon as possible and automated electronic notification would be the first step. If the accepting center declines the organ, then a match run could be re-run with the correct Human Leukocyte Antigen (HLA). Should there be a policy requirement for post-procurement and pre-transplant? Yes. Once procurement has occurred, while the automated electronic notification could remain the same as above, the reallocation with a new match run might cause unnecessary delays and potential organ discard. One could consider a local backup option or other expedited forms of placement to maximize organ utilization. Should there be a requirement to re-execute a match run if there is a critical HLA discrepancy? No. If the primary accepting center has said “yes” and is willing to take accept the discrepancy, the offer should still stand. However, if the primary center declines (for the primary patient), then a re-run would be appropriate if it is pre-procurement. When after procurement, see the response above. Are the proposed notification timelines reasonable? Yes, in most circumstances. If the error is a simple transcription error, then the timelines are reasonable. But if it is a true typing error, the timelines are not reasonable. See the following detailed comments. HLA typing errors, whether in a donor, candidate, or recipient, are almost unpreventable. They can occur at the pre-analytic/analytic stages, for example, by the simple act of misidentification of the specimen(s). There is currently no barrier to inadvertent misidentification although universal barcoding would go a long way toward preventing it. Errors can occur at the analytic stages from production of primary HLA typing data that is incorrect or of poor quality or from misinterpretation of primary data. Even when everything else is correct, error can creep in at the interface stages between instrumentation and computerized reporting mechanisms, especially whenever there’s a human involved in transcribing the data entries. Most laboratories performing HLA typing for the OPTN have robust systems to prevent and detect typing errors. Deceased donor typing errors can be detected pre-allocation but it is more likely for them to be detected post-allocation. The lab can discover HLA typing errors from their own internal quality control processes but it is more likely that the lab learns of a discrepancy from an external source like an OPO, an external transplant program, or from the OPTN itself through the discrepancy report or a patient safety report. This proposal makes no mention of reporting critical HLA discrepancies through the patient safety events portal. Critical HLA discrepancies are a patient safety issue. The proposal lacks clear development and delineation of responsibilities for reporting critical HLA discrepancies as patient safety events. Specifically, what type of HLA discrepancies should be reported as patient safety events? Who should make such reports, the host OPO, the lab originating the donor report, the transplant center(s) accepting organs, or all of the above? Are the proposed notification timelines reasonable? Donor HLA discrepancies can have trivial or more complex explanations. Clerical error is relatively easy to detect and determination of correct HLA can be made quickly. When a discrepancy results from a difference between a host OPO HLA laboratory result and an accepting transplant center’s confirmatory HLA, it might take more than 12 hours to determine the “correct” donor HLA depending upon the root cause. The discrepant labs would most certainly be employing distinct test systems and instrumentation as well as different specimens: it might not be immediately clear which of two discrepant HLA was correct. By 12 hours after receiving documentation of a discrepancy, reallocation would likely be precluded. At that juncture, it seems more important to take whatever time is necessary to make a final determination of the “correct” HLA. Ultimately, the laboratory producing the “incorrect” HLA report must discover the root cause for the discrepancy in order to put systems in place to prevent future error and this can take time, more than 12 hours. Ultimately, we feel that the Histocompatibility Committee should take better account of the nature of the root causes for HLA discrepancies and how and by whom they were uncovered before trying to devise policy regarding timelines for notification. Region 1 | 03/23/2021 OPTN Histocompatibility Committee Region 1 sentiment: 2 strongly support, 3 support, 1 neutral/abstain, 0 oppose, 0 strongly oppose American Society of Transplantation | 03/22/2021 The American Society of Transplantation strongly supports this policy change to ensure the accuracy of Histocompatibility data within UNet to improve patient safety and transplant outcomes. We agree with the suggested automated electronic notification be included in the implementation. The suggested timeframes appear reasonable given patient safety and the large number of imported organs (outside typing) for highly sensitized candidates. However, we suggest consideration to reduce the timeframe for the OPO to notify all accepting transplant programs to 8 hours from the proposed 12 hours. We also suggest a second minor addition for your consideration: Notification of a “Critical HLA Discrepancy” be sent to both the OPO and originating HLA Lab within 1 hour. This will immediately engage all parties and expedite the resolution of the HLA typing discrepancy. NATCO | 03/22/2021 NATCO commends the OPTN Histocompatibility Committee for bringing forward this long overdue topic of communicating HLA discrepancies. NATCO supports required communication of HLA discrepancies between HLA labs, transplant centers, and OPOs since this is a serious safety issue for transplant recipients that could lead to hyperacute rejection. An automated electronic notification could be helpful; however, if the discrepancy is found in real time prior to donor recovery, then HLA labs should be required to verbally communicate this to the OPO immediately upon finding the discrepancy in case re-execution of a match run is warranted and to notify all accepting centers. Re-generation of a match run should be the decision of the OPO with input from the Medical Director. Post-case notification could be done similar to patient safety reporting now with a 24 hour window for HLA labs to notify OPOs and/or transplant centers. Additionally, the communication of critical HLA discrepancies should be included in policy. Transplant Coordinators Committee | 03/19/2021 The Transplant Coordinators Committee thanks the Histocompatibility Committee for presenting its proposal “Require Notification of HLA Typing Changes” and offers the following feedback: A member emphasized the importance for timely notification of changes within HLA typing to allow for any necessary changes on their end and suggested an electronic form of notification as an option. Members shared their support for this proposal and echoed the comments of timely notification of changes. A member suggested reducing the notification deadline from five days and using a consistent notification process similar to what is currently used for culture results. It was also suggested that there be a coordinated notification process that would include the OPO, Histocompatibility Lab, and Transplant Center. Henrico Doctors' Hospital | 03/19/2021 We strongly support the comments provided by ASHI in regards to running a new match and also adding the originating HLA lab to the notification process. Kidney Transplantation Committee | 03/18/2021 The Kidney Committee thanks the Histocompatibility Committee for work in developing this proposal and appreciates the opportunity to provide feedback. The Kidney Committee supports the proposal, and provides the following feedback: automated notifications should be included in implementation, particularly as they are trackable. Required match re-execution for HLA typing changes may not be necessary, as OPOs have the ability to continue down Policy 5.9: Released Organs should a recipient be unable to receive an organ. Region 11 | 03/18/2021 Region 11 sentiment: 2 strongly support, 6 support, 3 neutral/abstain, 0 opposed, 0 strongly opposed No comments OPTN Operations & Safety Committee | 03/12/2021 The Operations and Safety Committee thanks the OPTN Histocompatibility Committee for their efforts in developing this public comment proposal, Require Notification of Human Leukocyte Antigens (HLA) Typing Changes. The Committee supports this proposal. The Committee supports leaving the decision to re-execute the match run on a case by case basis, rather than mandating. The Committee suggests strongly encouraging organ procurement organizations (OPOs) to re-execute the match run if incorrect HLA typing is known prior to organ acceptance. The Committee supports efforts in providing automated electronic notifications, especially if a match run has been executed and HLA has been entered. The Committee suggests the electronic notification system for infectious disease testing could be used as a model. The Committee suggested that reporting processes could mirror the process for potential disease transmission. This process could specify OPO notifications that should go to the patient safety contact, and alert the OPO to notify the transplant program’s patient safety contact. The Committee notes that the time of 24 hours for HLA is the same as potential disease transmission. Additionally, the histocompatibility lab would need to be able to demonstrate documentation the notification policy was followed, similar to the potential disease transmission process. Region 7 | 03/12/2021 Region 7 sentiment: 1 Strongly Support; 6 Support; 2 Neutral/Abstain; 0 Oppose; 0 Strongly Oppose. An attendee suggested defining “critical change” to better understand the HLA typing changes. Region 6 | 03/09/2021 Region 6 sentiment: 6 strongly support, 17 support, 4 neutral/abstain, 0 oppose, 0 strongly oppose. No comments or questions. OPTN Organ Procurement Organizations Committee | 03/09/2021 The OPO Committee supports the proposed changes and discussed the following: Most critical discrepancies were due to transcription errors. Therefore, even with the current dual-entry verification for donor HLA typing, which flags mismatches at each locus, it would not identify errors that have been incorrectly entered twice. There was a recommendation to automate the notification of HLA typing discrepancies. However, there were concerns about the logistical challenges of notifying certain members, noting that automated notification of donor typing changes may be more streamlined than for candidate typing changes. There was a question raised about whether there was discussion about a timeframe for re-executing the match run similar to changes in infectious disease testing results. The Histocompatibility Committee representative noted that such timeframes were not developed as part of this proposal but added that typing changes discovered post-procurement should be reported as soon as possible, as immunological concerns can be mitigated early on. There was a question raised about how an HLA discrepancy is determined to be critical enough to rerun a match run. The Histocompatibility Committee representative clarified that this would be the OPO’s discretion, and that this proposal would not mandate re-execution of the match runs. Region 8 | 03/09/2021 Region 8 sentiment: Strongly support-2, Support-6, Neutral/abstain-2 Oppose-0, Strongly oppose-0 There were no comments or questions ANNA | 02/25/2021 ANNA supports this proposal. Region 5 | 02/19/2021 Region 5 sentiment: 3 strongly support, 20 support, 2 neutral/abstain, 0 oppose, 0 strongly oppose. No comments or questions Region 3 | 02/18/2021 Region 3 sentiment: Strongly support-1, Support-15, Neutral/abstain- 1, Oppose - 0, Strongly Oppose – 0. This was not discussed during the meeting but OPTN representatives were able to submit comments with their sentiment. A member recommended 1 hour and 24 hour notification timelines consistent with OPTN policies 5.5 and 15.4. Region 4 | 02/04/2021 Region 4 sentiment: 3 strongly support; 12 support; 2 neutral/abstain; 0 oppose; 0 strongly oppose. Region 4 had no comments for this proposal. University of Illinois Chicago | 01/21/2021 Any change in deceased donor HLA typing performed by OPO must be communicated to transplant laboratories ASAP as this impacts risk assessment and post-transplant DSA monitoring. Currently we do not accept organs without a physical cross match. However, if we decide to accept organs based on virtual cross match for sensitized recipients, expeditious accurate donor typing is critical. This proposal brings to light the possibility of error in donor HLA typing and the risk associated with a virtual cross match.