VCAs from living donors

Goals

Background

Reconstructive VCA Transplants

Non-Reconstructive VCA Transplants

Ethical Principles

OPTN Role

Recommendations

References

Goals

The Organ Procurement and Transplantation Network (OPTN) Final Rule was amended by the Secretary of the U.S. Department of Health and Human Services (HHS) to include vascularized composite allografts (VCAs) as “covered human organs” effective July 3, 2014 (OPTN, 2014). With that directive, the OPTN was charged with the oversight of VCA procurement and transplantation. HHS has stated that the definition of VCA organs in the Final Rule does not prohibit the living VCA donation and has affirmed that oversight of living donation of all types, including living VCA donation, falls under the OPTN.

Unlike traditional life-saving organ transplantation for which the deceased donor supply is far short of the need and living donor transplants reduce the mortality of some forms of end-stage organ failure, the goals of VCA transplants are restorative or life-enhancing. Furthermore, VCAs procured from deceased donors are likely to meet or may exceed demand, although there may be exceptions in some situations. VCAs comprise a heterogeneous category of “organs” that include face, limb, long bones and soft tissues. Reproductive organs (e.g., uterus) are also considered VCAs, and the limits of VCA transplantation will continue to evolve. However, there will be some types of VCA organs that should never be donated by a living person. Because living VCA donation is a nascent field with boundaries that have not yet been defined, policies do not yet exist that define categories of VCA for which living donation may or may not be suitable. Nor have minimum requirements for protection of living VCA donors yet been specified in policy, including criteria for living donor recovery programs, recommendations for informed consent, and for medical and psychosocial evaluations.

Until policy is created and implemented to protect living VCA donors, the OPTN has developed this guidance document to address some general considerations regarding VCA types that may be suitable to consider from living donors, given the likely risk-benefit profile for these donors. Guidance is provided regarding criteria for programs, and recommendations for the informed consent, and medical and psychosocial evaluation of the living donor. The donation of every VCA type brings distinct medical, psychosocial and functional risks. It should be recognized that there are many different types of VCA donation and given the individualized nature of the reconstructive and non-reconstructive VCA procedures, the specific risks of each cannot be encapsulated or covered by general principles. Furthermore, the presence of guidance that addresses some types of living VCA donors cannot be taken as an endorsement of all types of living VCA donors, particularly in instances where unacceptably serious physical disfigurement, and/or psychosocial disability resulting from the donation are inherent results of the procedure itself.

Background

The performance of living donation in solid organ transplantation has become an accepted practice and an important source of organs particularly for kidney and liver transplant recipients although lung, pancreas, and intestinal transplants have also occurred. For life-saving organs, the scarcity of deceased donor organs has medically and ethically justified the benefits of living donation to the recipient; living donor transplantation confers a decreased chance of dying or becoming increasingly ill while awaiting transplantation. Despite these advantages to potential living donor recipients, the transplant community remains steadfastly united in supporting the overarching principle of minimizing the risks to the living donor is the highest priority and therefore donor risks must always be balanced against the benefit and risks to the recipient (Abecassis, M., et al., 2000). Although a decline in living donation has been observed in the United States, living organ donation has increased worldwide and important practices have been developed that focus on protecting the welfare of living donors. These include the implementation of standards addressing the special considerations for obtaining informed consent from a potential living donor (Thiessen, C., et al., 2013 and 2014), the use of an independent living donor advocate in the living donor evaluation process (Hayes, R.E., et al., 2015), and important ethical considerations which include the avoidance of donor coercion (Ethics Committee of the Transplantation Society, 2004).

Living donor kidney transplantation evolved more rapidly as compared to other living donor transplants, and consensus guidelines were first developed and adopted by the international kidney transplant community culminating in the Amsterdam Forum in 2004 (Ethics Committee of the Transplantation Society, 2004, and Delmonico, F., 2005). However, extra- renal living donation posed unique issues that were not addressed by the kidney living donor guidelines. In response to this need, an international conference was convened under the auspices of the Ethics Committee of The Transplantation Society (TTS) in 2005 (Barr, M.L., et al., 2006). The purpose of this meeting was to establish ethical principles and organ-specific guidelines for extra-renal living donor transplantation. The published proceedings from this meeting, which articulated general principles as well as specific recommendations, remain the backbone of concepts now formalized in CMS requirements and OPTN policies, and serve as an important and relevant source for the development of principles and ethical considerations for VCA living donation. Particularly relevant is the TTS Ethics Committee statement that living donation should only be performed “when the aggregated benefits to the donor-recipient pair out-weigh the risks to the donor-recipient pair” (Pruett, T.L., et al., 2006). Special emphasis was placed on respect for donor autonomy and the processes of informed consent. The meeting also addressed donor selection and the responsibilities of the transplant team performing living donor organ recovery.

Until very recently, the VCA transplants performed worldwide have been almost exclusively upper limb and face transplants (Shores, J.T., Brandacher, G., Lee, W.P., 2015), and the possibility of living donation was not considered given the unacceptable loss of function and disfigurement that would occur to a living limb or face donor. However, with the success of upper extremity and face transplantation, the use of different, less extensive types of VCA is broadening, and the possibility of utilizing a living VCA donor is now medically feasible and may be ethically appropriate for both reconstructive and non-reconstructive (e.g.: reproductive organ) types of VCA transplantation. Reconstructive (also known as “restorative”) VCA transplantation is intended to restore musculoskeletal function and/or body form to the affected recipient in the setting of trauma, tumor, infection, and congenital differences. Non-restorative VCA transplantation, such as uterine transplantation, restores lost or missing non-essential function (reproductive, in this example) to an otherwise healthy individual. The projected benefits of VCA transplantation and the justification of living VCA donation, in particular, are anticipated to differ between the various types of reconstructive and non-reconstructive VCAs.

Reconstructive VCA Transplantation and the Potential for Living Donation

To better understand the application of VCA transplantation within the broad concepts of reconstructive surgery, some overview is helpful. This perspective may help to explain how the consideration of living VCA donation has evolved within the ethical framework of living donation in general, which places the highest priority on minimizing risks to the donor and a high priority on respect for the donor’s autonomy. The “reconstructive ladder” is the concept that guides reconstructive surgeons to first select simple (lower rungs) and if needed, more complex (higher rungs) reconstructive procedures that meet the reconstructive needs of a particular patient (Levin, L.S., 2013). For example, a simple reconstructive technique is the use of skin grafting. A more complex procedure such as re-implantation of a traumatically amputated digit may necessitate use of the operating microscope to perform microvascular anastomosis of arteries and veins as well as microsurgical nerve repair. Autologous free tissue transfer or transfers of living tissue from one area of the body to another on its vascular supply. Examples include a microsurgical toe-to-thumb transfer or using parts of the abdominal wall transferred to the chest in order to reconstruct the breast after mastectomy.

In 1998, the field of VCA transplantation was introduced following the first hand allotransplantation in France (Dubernard, J.M., et al., 1999). This event marked the recognition that VCAs are the logical next step in reconstructive microsurgery, and that surgical techniques used in conventional reconstructive microsurgery can be successfully utilized in VCA transplantation. This landmark case ushered in the era of “restorative surgery.” Although “higher” on the “reconstructive ladder,” by utilizing the exact missing composite tissues from a deceased donor, VCA transplantation offered the recipient the possibility of fewer reconstructive surgeries and more natural function and physical appearance. The recipient would now require life-long immunosuppression in order to prevent immune rejection of the allograft(s), but in exchange, would be spared the morbidity and possible disfigurement of conventional reconstructive procedures that required the use of tissue(s) from elsewhere on the patient’s body. This first case, however, also highlighted unknown psychosocial issues surrounding VCA transplants, as the recipient sustained significant unfulfilled expectations and ultimately requested removal of the VCA graft. Sixteen years following the hallmark case in France, there have been 110 upper extremity and 30 face VCAs transplants performed from deceased donors with highly encouraging outcomes. VCAs are now accepted as a viable option for patients with reconstructive needs that cannot be realized with conventional reconstructive methods, despite the array of complex and powerful reconstructive microsurgical procedures currently available. The risks of immunosuppression in these patients have been balanced against the benefits of VCA reconstruction that cannot currently be matched by options lower on the “reconstructive ladder.”

In response to the success of VCA transplantation and its increasing utilization in the U.S., the Secretary of HHS amended the OPTN Final Rule in 2013 that defined a VCA, meeting specific conditions, as an organ, making it therefore subject to the oversight of the OPTN as set forth in NOTA. The amendments to the Final Rule were effective on July 3, 2014 and did not stipulate a list of specific VCAs that would be considered as organs. This was in recognition that many possible VCAs were likely – some as complex as face and extremities, and others of more limited extent such as portions of the abdominal wall. Since then, the OPTN has approved policies addressing membership, donor authorization, allocation, and data collection for VCA transplantation (OPTN, 2014 and 2015).

The Secretary of the HHS responded to public comments on the proposed amendment to the OPTN Final Rule. Specifically, the HHS clarified that the definition of VCAs as organs in the Final Rule does not prohibit the possibility of living VCA donors. The Secretary affirmed that oversight of living donation of all types falls under the auspices of the OPTN. As the indications for life altering VCAs expand, and new areas of deceased donor allotransplants are developed (e.g.: lower extremity, urogenital, larynx, joint transfers), consideration of living donation for specific types of VCAs should therefore be included within the possibilities for the future. In fact, as described in the microvascular reconstructive literature, there are several examples of living donor VCA transplants that have already been performed, both in the U.S. and internationally. Harry Buncke, a founder reconstructive microsurgery, transplanted the omentum between twins for scalp reconstruction in 1982 (Buncke, H.J., 1982). More practically, Robert Allen has transplanted abdominal wall tissue for breast reconstruction following mastectomy between identical twin sisters (Allen, R.J., et al., 2008). The lack of need for immune modulation in these identical twin-to-twin living VCA donor transplants clearly distinguishes such transplants from other forms of organ transplantation. There are many potential examples of cases such as limb salvage or large, soft tissue reconstruction for tumors and malformations where the patient’s autologous tissue is insufficient to complete the reconstruction – a concern particularly relevant for pediatric patients. It is expected that VCA transplants could solve this problem of autologous tissue shortage. While living donor limb transplantation (whole or partial) and face transplantation are not endorsed, if deceased donation options were exhausted, living VCA donation utilizing the equivalent of conventional free-flaps may be a consideration. Equally important to any patient and particularly relevant to the discussion of living VCA donation, is the recognition that in some instances, there may be acceptable non-tissue alternatives, such as prosthetics (e.g. breast implants or prosthetic limbs). Non-tissue alternatives should be carefully weighed against any reconstructive option that utilizes tissues from the patient, from a deceased donor or from a living donor.

Taking into consideration the progress in VCA transplantation to date, the reconstructive transplant surgical community is anticipating that a VCA from a living donor could be considered under specific circumstances. First, living VCA donation must provide added benefit to the recipient (over available alternatives—specifically, deceased donor VCA) and donor. Second, the risk to the donor must be low in relation to the benefits to be gained by the recipient. Third, the process of informed consent for the donor must define, to the extent possible, the likely risks of donation and likely outcomes for the recipient. Although there is currently no known shortage of deceased donor VCA organs, access to a deceased donor organ may be limited in some circumstances. The infrastructure, both logistically and socially, to provide adequate numbers of deceased donor VCAs is still in development. There are situations in which the temporal availability of an appropriate VCAs from deceased donors may limit the use of this preferred reconstructive option. For example, trauma related clinical scenarios (Bremen, L.F., Mazurek, M., 2010) could present challenges in securing a deceased VCA donor in a timely manner (e.g., within days following trauma). In these cases, living VCA donation may provide the benefit for salvage of an injured patient’s limb. Such a scenario, however, might pose challenges to the donor’s informed consent if donor evaluation and informed consent had to take place under time pressure. In other circumstances, difficulties in finding a suitable deceased donor for reconstruction following the surgical treatment of extensive tumors (Eward W., et al., 2010), or for the correction of congenital malformations (Jones, N.F., Hansen, S.L., Bates, S.J., 2007) may lead to psychological trauma for the patient should they need to endure a prolonged wait for suitable tissue, particularly in pediatric cases. Finally, HLA matching for transplantation has been associated with better outcomes in adult solid organ transplantation (Shanmugarajah, K., et al., 2014). It is possible that HLA matching may play an important role in VCA transplantation, and living donation from related persons may be beneficial, similar to current HLA matching for bone marrow or solid organ transplants.

Non-reconstructive VCA Transplantation and the Potential for Living Donation

Another example of living donor VCA transplantation is uterine transplantation (Brannstrom, M., et al., 2014). Living donor uterine transplantation theoretically offers the possibility that a woman, perhaps a sister or mother, may donate her uterus, provided she is finished with child bearing or chooses not to bear children. If the donor was an identical twin sister, this example would have the added benefit of transplantation without the need for immunosuppression. Most recently, Brännström et al. reported the first live birth after uterus transplantation from a living donor (Brännström, M., et al., 2014). The intent of uterine transplant - to provide a life enhancing, but non-vital organ - is more in keeping with the intent of other VCAs, as compared to life saving traditional organ transplants. The mandate to protect living donor safety is incontrovertible (Kisu, I., et al., 2013). To that end, any consideration given to living VCA donation for non-reconstructive purposes, such as infertility, must take into consideration the availability of alternatives, such as deceased VCA donor transplantation.

Ethical Principles When Considering the Living VCA Donor

Compared to traditional living donor organ transplantation, living VCA donation does not offer the benefit of a life-saving procedure, it does share some of the same similarities and should be guided by the same ethical principles. These principles include the concepts of nonmaleficence or minimizing risk for the living donor, and respect for the donor’s autonomy (Thiessen, C., et al., 2015). The ethical practice of transplantation of grafts from living VCA donors will rely on a thorough medical and psychosocial evaluation of the living donor, confirmation that the decision to donate is consistent with the donor’s values, and the process of informed consent.

Living VCA donation differs from other forms of living organ donation in several ways. First, the benefit to the recipient of VCA transplantation involves improvement in function or quality of life rather than in survival. The TTS Ethics Committee statement noted that living donation should only be performed “when the aggregated benefits to the donor-recipient pair out-weigh the risks to the donor-recipient pair”. Therefore, when the transplant team evaluates the risk-benefit ratio for the living VCA donor, it is critical to consider and discuss with the recipient and donor, that the recipient may have other options available. These might include use of autologous tissue or continuing to wait for a deceased VCA donor. Second, unlike living organ donation (such as kidney donation), an important risk that some living VCA donors have is substantial, physical or psychosocial changes including disfigurement and permanent loss of physical function. There may be as yet undefined psychosocial consequences as well. Consideration of the physical, functional, and psychosocial consequences to the living VCA donor, by both the surgeon, the potential donor and the potential recipient, in as specific terms as possible, is central to the ethical application of VCA to living donors. Understanding the consequences to the recipient and to the donor-recipient relationship following living VCA donation also poses extraordinary challenges that must also be carefully explored by the medical team, donor, and recipient.

Moreover, when weighing risks and benefits, the transplant team and potential living donors should consider that the benefits that are gained by recipients of live donor kidney or liver transplants do not readily apply to recipients of living VCA donor transplants. A major benefit of living donation for solid organ transplants (e.g., liver or kidney) is the avoidance of long waiting times and accompanying greater chances of dying. By contrast, the lack of shortage of VCA deceased donor transplants eliminates the need to wait for a transplant, and reduces the traditionally known benefit of, and therefore need for, living VCA donors.

The concept of living VCA donation can be supported only as long as an unacceptably severe permanent disability or disfigurement to the donor does not occur. For that reason, donation of limbs or faces from living donors is not supported by the OPTN.

The Role of the OPTN in Oversight of VCA Living Donation

With the designation of VCAs as “covered human organs”, the OPTN has not only the authority, but also the requirement to develop policies that oversee VCA transplantation practice and allocation, and maintain compliance with NOTA and directives from HRSA. As the Final Rule does not exclude the possibility of living VCA donation, and, as living donor VCA transplants have already occurred, it is essential that the OPTN moves expeditiously to develop policy to uphold the essential principle of protecting living donor safety applicable across all organs, including VCAs. In the interim, these guidelines address some general considerations regarding living donor VCAs, the likely risk-benefit profile for these donors, and provide recommendations concerning the informed consent and medical and psychosocial evaluation of these individuals.

There is an established precedent within the OPTN for the development of policy to govern living donation (Brown, R.S., Higgins, R., Pruett, T.L., 2009), and we propose that this rigor be equally applied to living VCA donation. The Living Donor Committee responded to a 2006 directive from HRSA published in the Federal Register to develop policies for all living donors. These policies were to include informed consent and medical and psychosocial evaluations. Initially, voluntary guidelines were developed for donor informed consent and for the psychosocial/medical evaluation of living kidney and living liver donors. No specific guidelines were in place for other living donors such as lung, pancreas or intestine donors.

The Living Donor Committee worked collaboratively over the subsequent years with other UNOS committees and with the Joint Societies Working Group (American Society for Transplantation - AST, American Society for Transplant Surgeons - ASTS, and the North American Transplant Coordinators Organization - NATCO) to formulate policies specific for living kidney donation. As a result, policies were approved by the OPTN Board of Directors in November 2012 for living kidney donation. The Living Donor Committee, working again with the Joint Societies Working Group, considered policies specific to living liver donation. The Living Donor Committee felt that the same consideration should be given to other living organ donors and in 2013 proposed policies to govern all living organ donors. These policies also incorporated specific requirements in the cases of living kidney and liver donors. These policies, and their public comment, understandably evolved over several years without consideration for living VCA donors. Therefore when the living donor policies were approved by the OPTN Board in November 2014, these policies pertained only to living kidney, liver, lung, pancreas and intestine donors (OPTN, 2015).

The VCA, Living Donor, and Ethics Committees are keenly aware that the current living donation policies do not include VCA living donation. The VCA Committee is of the strong opinion that, in view of some public and professional uncertainty regarding the role of living donation in VCA transplantation, it is essential to establish guidelines appropriate for living VCA donation that are transparent and easily available to the public. These guidelines should uphold the established principles of living donation across all organ types. As well, the adoption of these guidelines should be consistent with the requirements already contained in the current living donor policies. However, it must be recognized that there are many different types of VCA donors whose specific risks cannot be encapsulated or covered by general principles. Furthermore, the presence of guidelines that cover some types of living VCA donations cannot be taken as an endorsement of all types of living VCA donation. In fact, there will be some types of VCA organs that should never be donated by a living person. In other circumstances, an acceptable VCA transplant procedure involving living donation may not be possible because the urgency of the procedure is too great and could lead to undue pressure on and possibly coercion of the donor.

The Living Donor and Ethics Committees agreed with the need for a Guidance Document for VCAs from living donors and have been extensively involved in the thoughtful development of this document. The VCA, Living Donor and Ethics Committees endorse this guidance document and also the development of future policies that will address living VCA donation.

The initial step in this process is this Guidance Document that provides resources and general recommendations to assist VCA transplant programs that are beginning to consider living donor VCA transplantation. This approach is consistent with other precedents that developed OPTN Board of Directors-approved guidance documents for living donor kidney and liver transplantation, prior to the development of policies.

The first level of oversight for living VCA donation in lieu of actual policy is the strong recommendation that living VCA donor programs submit their protocols to the OPTN. Furthermore, we recommend that these protocols be reviewed and approved by the transplant hospital’s Ethics and Institutional Review Boards. Those protocols submitted to the OPTN would assist in the development of future OPTN policy proposals for VCA living donation. The process of OPTN policy development for VCA living donation would then ensure that input is obtained from the relevant OPTN committees and professional societies. After a consensus agreement is reached, the proposal would be presented for public comment. If approved by the Board, the VCA-specific policies could be incorporated into current living donor policies as specific VCA requirements in keeping with the same concept already in place for kidney and liver living donation. This process may take up to 18 to 24 months. In the interim, the VCA Committee strongly supports this Guidance Document as the first step in fulfilling the Committee’s responsibility to move forward with the development of VCA-specific policies, including the possibility of living VCA donation, and to address public comment in regards to the ethical and safe practice of living VCA donation. Assurances that the practice of living VCA donation will ultimately be governed by policies that are consistent with the central principle of protecting donor safety, including requirements for informed consent and psychosocial and medical evaluations of potential living VCA donors are needed for the OPTN to remain in compliance with NOTA and the 2006 directive from HRSA.

Recommendations for Programs Performing Living VCA Donation

OPTN Bylaws, Appendix J requires that recovery hospitals must have received approval for and maintain an active VCA program. Transplant hospitals that perform living VCA donor transplants must only accept and transplant living VCA donor organs recovered at hospitals with current transplant program approval for the same VCA type (See OPTN Policy 14.6.C). In addition to these requirements, it is highly recommended that:

• The living VCA donor recovery hospital should be approved by the OPTN for another type of living donor recovery in order to provide institutional expertise and guidance to the living VCA donor program.
• The VCA program should submit their informed consent, medical, and psychosocial evaluation protocols for living VCA donation to the OPTN. These protocols may be used to develop future OPTN policies and bylaws for living VCA donation.
• A transplant hospital that plans to recover VCAs from living donors should obtain their own institutional Ethics and Institutional Review Board approvals of their informed consent, medical, and psychosocial evaluation protocols.
• The VCA program should provide a “Statement of Need” approved by their own institutional Ethics and Institutional Review Boards outlining the following items:
• Any benefit the donor may gain from the procedure;
• The risk of permanent disability incurred by the potential VCA donor that may exceed known complications of the surgical procedure, and why the donor may be justified to take this risk;
• Why the use of a deceased donor is not possible, or suboptimal for the proposed VCA procedure.
• Protocols for each type of VCA to be recovered from a living donor should address all of the following key elements detailed below under subheadings 1-7:
1. Independent Living Donor Advocate (ILDA) Recommendations
2. Informed Consent Recommendations
3. Psychosocial Evaluation Recommendations
4. Medical Evaluation Recommendations
5. Living Donor Follow-up
6. Medical Evaluation after Living Donation
7. Other considerations
• The recovery hospital submit to the OPTN the institutionally approved operative consent form to be used for each type of proposed VCA procurement from a living donor. This consent form should include the elements specified under subheading 2 (Informed Consent Recommendations) below.
• The VCA program must identify the Surgical Director responsible for compliance with the recovery hospital’s living VCA donor informed consent and medical/psychosocial evaluation protocols.

OPTN policy specifies requirements for ILDAs, informed consent, and medical and psychosocial evaluation requirements for living liver, kidney, pancreas, intestine, and lung donors. In addition, OPTN policy specifies living donor follow-up requirements for kidney and liver donors. These policy requirements were based on extensive work by the Living Donor Committee as well as recommendations from experts on a Joint Societies Steering Committee (AST, ASTS, and NATCO). To date, there has not been an opportunity to follow this same process for living VCA donors. The Joint Societies Steering Committee has communicated their interest in collaborating with the OPTN on future policy development in this area.

The recommendations that follow were made by an OPTN working group from the OPTN VCA, Living Donor and Ethics Committees, and were largely drawn from OPTN Policy 14 (14.1-14.8) with appropriate additions relevant to VCA. The recommendations that follow should be viewed as minimum suggested elements, and should apply to VCA living donation until policies specific to living VCA donors, and specific to different types of VCA living donation, can be developed. The living donor recovery hospital should tailor the informed consent, and psychosocial and medical evaluation to the specific type of living VCA donation to be performed, as deemed appropriate by the transplant team. To date, the risks to donors of many types living VCA donation is not known.

1. Independent Living Donor Advocate (ILDA) Recommendations

The living VCA donor recovery hospital should develop and, once developed, comply with a protocol to provide an ILDA who advocates for the rights of the living VCA donor and who will assist the donor during all phases of the consent process and the psychosocial and medical evaluation process. The ILDA should be available to assist the donor after VCA donation as well. The ILDA may be one person or an ILDA team with multiple members. The recovery hospital should include in their protocol the following elements, adapted from OPTN Policy 14.2.

• The designated ILDA should not be involved with the potential recipient evaluation and should be independent of the decision to transplant the potential recipient.
• If the recovery hospital uses an ILDA team instead of an individual person as an ILDA, the ILDA team should designate one person from the team as the key contact for each living VCA donor.
• The ILDA should fulfill qualification and training requirements that the recovery hospital specifies in their protocol, including knowledge of living VCA organ donation and transplantation, medical ethics, informed consent, and the potential impact of family or any other external pressure on the living VCA donor’s decision about whether to donate.
• The ILDA should review whether the living VCA donor has received information, and assist the donor in obtaining additional information from other professionals as needed, in the areas of informed consent, the evaluation process and requirements, medical and psychosocial risks, the recovery hospital’s requirements for living VCA donor follow-up, and the benefit and need for donor participation in follow-up.
• The recovery hospital’s protocol for the ILDA should specify any other required duties and responsibilities of the ILDA, and should also specify the process for the ILDA to file a grievance to protect the rights and best interests of the living donor, as well as the process that will be used to address any grievance raised by the ILDA concerning the rights or bests interests of the donor.

2. Informed Consent Recommendations

Living VCA donor recovery hospitals should:

A. Develop, and once developed, should comply with written protocols for the Informed Consent for the Donor Evaluation Process and for the living VCA donation procedure. These written protocols should include the recovery hospital’s approved operative consent forms, and if obtained the Institutional Review Board-approved protocol(s), that will be used for the type of VCA procurement being considered for a given donor. All consent forms and other educational information provided to donors should be written at a fifth grade reading level, and provided in the donor’s native language. When necessary, independent interpreters should be provided to make certain the potential donor comprehends all information and other communications from the recovery team. The protocol should ensure that, when possible, the donor has sufficient time to reflect (a “cooling off period” after receiving informed consent materials and related education.

B. Provide to the living VCA donor the evaluation protocol and operative consent forms and obtain the donor’s signature on these documents that confirm that the donor:

• is willing to donate,
• is free from inducement and coercion,
• acknowledges that it is unlawful to knowingly acquire, obtain or otherwise transfer any human organ for anything of value including, but not limited to, cash, property, and vacations,
• may decline to donate or opt out of the donation process at any time, and
• has the opportunity to discontinue the donor consent or evaluation process in a way that is protected and confidential.

C. Provide teaching or instructional materials, in any media the recovery hospital chooses, and including one-on-one interaction between staff and the donor, utilizing interpreters when needed as noted above. Media materials should be in a language in which the donor is fluent, and should address all phases of the living donation process, including informed consent; medical and psychosocial evaluations; pre- and post-operative care; and required post-operative follow-up.

D. Disclose the following:

• Living VCA donation is an experimental procedure
• The operative procedure to be used for the specific VCA procurement procedure and the operative technique for the restorative or reconstructive procedure to be used for the recipient after procurement, as well as the expected recovery time for the donor.
• The recovery hospital will take all reasonable precautions to protect the confidentiality of the donor and recipient. Information about the donor’s workup and decision making will only be disclosed to the recipient team if the donor provides consent for this information disclosure.
• The living VCA donor will be provided with an ILDA who will assist with all phases of the evaluation and donation process.
• Living VCA donation is intended to be life-enhancing but not life-saving for the recipient.
• The donor undertakes risk and receives no direct medical benefit from the donation. While donors may experience non-medical benefits from donation, these outcomes are uncertain.
• The possibility of visible physical change, including temporary or permanent disfigurement and loss of physical function for the VCA donor. Specific physical changes as a result of a specific type of VCA donation should be enumerated (e.g., inability to have children after donating a uterus).
• The alternative procedures or treatments available for the potential recipient, as appropriate to the proposed VCA:
  • Options may include deceased VCA donation,
  • Use of prostheses, or
  • In the case of a uterine transplant, options of surrogacy or adoption.
• Whether the intended recipient has or has not been registered on the waiting list for a VCA from a deceased donor.
• There is no apparent shortage of deceased donor VCAs, and the alternative is to wait for a deceased donor. VCA transplant candidates may continue to wait for a deceased donor VCA without incurring additional medical risks.
• Any transplant candidate may have risk factors for increased morbidity or mortality that are not disclosed to the donor
• The medical and psychosocial outcomes for the candidates of the type of VCA transplantation that is to be performed and for their living VCA donors, as well as the fact that the data are limited due to the small numbers of VCA transplants that have been performed to date. This information should include, but not be limited to:
  • how many such procedures have been performed:
    • (a) at the recovery hospital where the procedure is to take place,
    • (b) nationally, and
    • (c) internationally, and
  • one-year recipient and graft survival.
• The OPTN requires submission of living donor follow-up information for a period of two years post-donation for living liver and kidney donors. At this time, the OPTN does not have the same data collection mechanism in place for living VCA donors. Recovery hospitals are requested to report VCA living donor follow-up information for at least two years to help determine the short-term health impact of VCA living donation. Standardized data collection forms will be made available for living donor recovery hospitals to submit information voluntarily via secure email to the OPTN.
• The evaluation process will include a medical evaluation and a psychosocial evaluation of the potential donor (see subheading 3 and 4 below).
• Health information obtained during the evaluation is subject to the same regulations as all medical records, and could reveal conditions that must be reported to local, state, or federal public health authorities. Additionally, any infectious disease or malignancy pertinent to acute recipient care discovered during the donor’s first several years of follow-up care will be disclosed to the:
  • local, state, or federal public health authorities as required by law,
  • recipient’s transplant center, and
  • OPTN Improving Patient Safety Portal.
• There are inherent risks associated with the evaluation for living VCA donation. Some of these risks will vary depending on the specific type of donation, and recovery hospitals should enumerate the VCA-specific risks to the donor. In addition, general risks include:
  • Allergic reactions to contrast o Discovery of reportable infections
  • Discovery of serious medical conditions and adverse genetic findings unknown to the donor
  • Discovery of certain abnormalities that will require more testing at the donor’s expense or create the need for unexpected decisions on the part of the transplant team.
• Although many of the risks remain unknown, it is likely that there are medical, psychological, and financial risks associated with being a living VCA donor, which may include, but are not be limited to the following:
• Potential Medical Risks
  • Potential for surgical complications including risk of donor death;
  • Potential for loss of function, resulting in temporary or permanent disability
  • Potential for organ failure; o Potential for disfigurement or changes in physical appearance or physical functional status including:
    • a) the perception by the donor or by others of the donor’s disfigurement, and
    • b) stigmatizing interactions with others as a result; o Potential change in quality of life;
  • Potential for the need for a future VCA transplant for the donor; o Potential for other medical complications including unforeseen long-term complications;
  • Scars;
  • Pain;
  • Fatigue;
  • Abdominal or bowel symptoms such as bloating and nausea, and similar symptoms commonly associated with general anesthesia and the use of narcotic analgesia post-operatively;
  • Increased risk with the use of over the counter medications and supplements; and
  • Depression or other psychiatric disorders requiring medical intervention because of loss of physical function, permanent physical disability, or changes in physical appearance.
  • Other potential medical risks specific to the type of VCA as determined by the medical team
• Potential Psychosocial Risks
  • problems with body image specifically related to physical changes in, or loss of, body parts as a result of the VCA donation procedure.
  • post-surgery depression or anxiety or the development of other psychological adjustment problems related to physical changes resulting from the VCA donation procedure.
  • feelings of emotional distress or grief if the transplant recipient has a recurrence of disease, if the transplant fails and/or the VCA must be removed, if re-transplantation becomes necessary, if the recipient dies, or if there are other suboptimal outcomes from the surgery for the recipient.
  • changes to the donor’s lifestyle as a result of donation.
  • strain between the donor and his/her family if family members did not support the donation.
• Potential Financial Risks
  • neither the donor’s nor the recipient’s health insurance may cover donation expenses if procedures are viewed as experimental or as elective (given that VCA transplant is not life-preserving).
  • personal expenses of travel, housing, child care and lost wages related to VCA donation might not be reimbursed; however, resources might be available to defray some donation-related costs o loss of employment
  • negative impact on the ability to obtain future employment
  • negative impact on the ability to obtain or afford health, disability, and life insurance o future health problems experienced by living VCA donors following donation may not be covered by the recipient’s or donor’s insurance
  • follow-up health care after living VCA donation may not be covered by the recipient’s or donor’s insurance

3. Psychosocial Evaluation Recommendations

Living VCA donor recovery hospitals should develop and comply with written protocols for psychosocial evaluation of the potential living donor by a psychiatrist, psychologist, masters-prepared social worker or licensed clinical social worker with experience in transplantation (defined in OPTN Policy 14.1.A) to determine decision making capacity, screen for any pre-existing or current psychiatric illness, evaluate the donor’s coping skills and social supports, and evaluate whether the donor is experiencing undue pressure or any potential coercion.

The psychosocial evaluation should include, but not be limited to, all of the following:

A. An evaluation for any psychosocial issues, including mental health issues and issues related to body image that might complicate the living VCA donor’s recovery and could be identified as risks for poor psychosocial outcome after donation. The presence or history of suicidal ideation or attempts should be evaluated and documented.

B. An evaluation for the presence of behaviors that may increase the risk for disease transmission as defined by the U.S. Public Health Service Guideline.

C. A review of the living donor’s history of smoking, alcohol, and drug use, abuse, and dependency.

D. The identification of factors that warrant educational or therapeutic intervention before the final donation decision. If the evaluating professional identifies or suspects that the donor has mental health or substance use issues that could complicate donation, this professional should arrange for further psychological or psychiatric evaluation and treatment for the donor, before the recovery hospital reaches a decision as to the suitability of the donor candidate. The professional should reevaluate the donor regarding any such issues once the donor has received treatment in order to determine whether the donor is able to be considered as a potential VCA donor.

E. The determination that the potential donor understands the short- and long-term medical and psychosocial risks (insofar as such risks are known) for both the donor and the recipient associated with the specific type of living VCA donation under consideration.

F. The determination that the potential donor understands the short- and long-term outcomes (or understands that there is little to no information on such outcomes) of the recipient’s specific type of VCA transplant

G. The determination that the potential donor understands the recipient’s alternatives to the specific type of living donor VCA being considered, and that the VCA transplant may be life-enhancing for the recipient but is not considered a life-saving form of transplantation.

H. An assessment of the donor’s ability to cope with surgery, related stress, and the temporary or permanent physical changes that may result, included disfigurement, loss of function, and disability, after the specific type of donation to be undertaken. The assessment should also consider the donor’s ability to cope with an unexpected or poor recipient outcome.

I. An assessment of the reason(s) why the potential donor volunteered to donate and the nature of their relationship (if any) with the transplant candidate. The evaluator should attempt to determine whether the potential donor’s decision to donate is due to undue pressure and whether any coercion from any source exists.

J. An assessment of the donor’s ability to make an informed medical decision. This includes evaluating whether the donor has a realistic plan for donation and recovery, with social, emotional and financial supports available.

K. Review of the financial and social circumstances of the potential living VCA donor (e.g., employment, insurance coverage, living arrangements, social support.) including the potential of loss or impairment of physical function that might affect employment, lifestyle, and the ability to maintain or obtain health or life insurance. The evaluator should investigate the potential donor’s understanding of the possible financial implications of living donation and the availability of financial resources to cover costs related to the surgery as well as to post-operative care and care for any short- or long-term medical consequences of donation.

4. Medical Evaluation Recommendations

VCA recovery hospitals should develop and comply with written protocols for the medical evaluation of the potential living donors. These protocols will vary depending on the type of living donor VCA. Recovery hospitals should review Section 14.4 of OPTN policy for elements that should be included in their living donor VCA protocols, and their protocols should include, but are not limited to, the following elements:

A. General Medical History

Physicians should assess the potential living VCA donor for:

• Significant medical conditions such as hypertension, diabetes, lung disease, heart disease, gastrointestinal disease, autoimmune disease, neurologic disease, genitourinary disease, history of cancer, history of infections, hematologic disorders, and bleeding/clotting disorders;
• Smoking, alcohol and drug use/abuse, including intravenous drug abuse; • Medications consumed currently and in the past (chronic use of pain medications, other);
• Allergies;
• Family history (coronary artery disease, cancer, other);
• Social History including occupation, employment status, health insurance status, living arrangements, and social supports; and
• The presence of behaviors that may increase risk for disease transmission as defined by the U.S. Public Health Service (PHS) Guideline.

B. Physical Exam

• Height, weight, body mass index (BMI) and vital signs;
• Examination of all major organ systems; and
• Specific examination for proposed VCA – refer to “Anatomic Assessment (k) for additional recommendations.

C. General Laboratory Testing

• Complete blood count CBC with platelet count
• Prothrombin Time, INR, Partial Thromboplastin Time
• Coagulation profile (consider Factor V Liden), evaluation of hypercoaguable state in both the donor and recipient should be carefully assessed;
• Comprehensive panel (electrolyte, BUN, creatinine, calcium, phosphorus,)
• HCG quantitative pregnancy test for women < 55 years old
• Chest X-Ray
• Electrocardiogram (ECG)
• Evaluation for coronary artery disease, as suggested by the American College of Physicians
• Pulmonary function tests for smokers, as suggested by the American College of Anesthesiology and American Lung Association.

D. Immunological Testing

• ABO blood group typing
• HLA tissue typing
• Crossmatch

E. Metabolic Focused Testing

• Fasting blood glucose
  • The evaluation team may consider fasting cholesterol levels (Cholesterol, Triglycerides, HDL Cholesterol, and LDL Cholesterol) with Fasting Lipid Profile if cholesterol/triglycerides are elevated.
  • If the potential donor does not meet the definition of diabetes, but has a family history of diabetes or characteristics of metabolic syndrome, he/she should receive counseling about risk for developing diabetes and perhaps non-alcoholic fatty VCA disease.

F. Anatomic Assessment

The microvascular/reconstructive surgical team’s assessment of anatomy will vary with the proposed type of VCA, but will ultimately determine if the proposed VCA is anatomically suitable for transplantation into the recipient. For each type of VCA proposed, the surgical team will be asked to send a detailed surgical plan for the donor procurement and the recipient operation to the OPTN. For the donor, this should include:

• The specific tissue components of the VCA to be procured:
• Size/area/depth estimate of the VCA
• Assessment of physical compatibility match, if appropriate, of donor to recipient for characteristics such as skin tone, or size
• Pre-operative interventions necessary (such as angiography)
• Location
• Blood vessels to be procured
• Details of the reconstructive procedure for the donor after procurement
• Expected physical appearance after the procurement
• Expected functional loss, early and long term
• Potential procedure-specific surgical complications for the donor

G. Transmissible disease testing

This screening is used to identify the risk of transmitting an infection or disease to a recipient. This screening may also identify a condition that may require the donor to seek treatment or may increase the risk of donation. Infectious disease testing must comply with OPTN Policy (14.4.B, Table 14-6), including testing for the following:

• CMV (Cytomegalovirus) antibody; VCA or EBNA antibody test may be performed if the recipient is EBV seronegative
• EBV (Epstein Barr Virus) antibody;
• HIV antibody (anti-HIV) testing, or HIV antigen/antibody (Ag/Ab) combination test as close as possible, but within 28 days prior to VCA recovery;
• Hepatitis B surface antigen (HBsAg)* as close as possible, but within 28 days prior to VCA recovery;
• Hepatitis B core antibody (HBcAB)* as close as possible, but within 28 days prior to VCA recovery;
• Hepatitis C antibody (anti-HCV)** as close as possible, but within 28 days prior to VCA recovery; or,
• Syphilis testing

* HBV DNA should be considered if HBcAB is positive or in high risk individuals.

** HCV RNA should be considered in high risk individuals.For tuberculosis (TB), living donor recovery hospitals must determine if the donor is at increased risk for this infection. If TB risk is suspected, testing must include screening for latent infection using either:

• Intradermal PPD
• Interferon Gamma Release Assay (IGRA)

Depending on transplant program preference and donor risk profile, physicians may test for other diseases such as:

• Hepatitis B surface antibody (HBSAB);
• Human T-cell Lymphotropic Virus (HTLV 1) antibody testing;
• Lyme disease for donors from endemic areas
• Strongyloides for donors from endemic areas
• Trypanosoma cruzi for donors from endemic areas
• West Nile Virus for endemic areas
• Toxoplasmosis: Transmission is low if recipients are treated with trimethoprim- sulfamethoxazole

H. Cancer screening

Cancer screening tests should be performed at the discretion of the transplant teams and will vary on the type of VCA proposed. If performed the screening tests should follow the protocols consistent with the American Cancer Society (ACS) or the U.S. Preventive Services Task Force. Screenings that should be performed based on gender, age, or family history include:

• Cervical cancer
• Breast cancer
• Prostate cancer
• Colon cancer
• Lung cancer
• Recent malignancy or cancers with long times to recurrence (e.g., breast cancer);
• History of melanoma;
• History of metastatic cancer

I. Exclusionary Criteria

A variety of criteria may make an individual unsuitable for living VCA donation. A list of exclusion criteria to living VCA donation should appear in the recovery hospital’s protocols and include:

• Age < 18 years of age;
• Mentally incapable of making an informed decision;
• High suspicion of donor coercion
• Evidence that illegal exchange of anything of value between donor and recipient for donation exists
• Active malignancy or incompletely treated malignancy
• HIV
• Active TB or untreated TB infection;
• Active symptomatic infection
• Active psychiatric illness that precludes comprehension of risks and benefits of decision-making, including any evidence of suicidality and disorders of body image (e.g., eating disorders or body dysmorphic disorders)
• Current alcohol or drug abuse or dependence Other Exclusion Criteria to be considered:
• Age limit >60 years of age
• Diabetes;
• Significant history of thrombosis or embolism;
• Bleeding disorders;
• Morbid obesity;
• Clinically significant coronary and/or peripheral vascular artery disease;
• Neurological disease
• Current smoking
• History of alcohol or drug abuse or dependence
• Recent tattoos
• The presence of behaviors that may increase risk for disease transmission as defined by the U.S. Public Health Service (PHS) Guideline
• Pregnancy
• Severe functional limitation including neurologic disorders anticipated following donation
• Symptomatic valvular disease;
• Chronic lung disease with impairment of oxygenation or ventilation;
• Anatomic abnormalities in the donor VCA that make the likelihood of successful transplantation low, or increase the risk in the potential donor;
• Hepatitis C virus infection;
• Hepatitis B virus infection; and
• Human Immunodeficiency Virus

The OPTN Living Donor and VCA committees will consult with relevant experts in the transplant community to periodically review and update this resource until such time as formal VCA-specific policies are in place.

5. Living Donor Follow-up

The VCA living donor recovery hospital is requested to submit information to the OPTN about the status of each living donor for a minimum of two years following donation. Within the first two years, information should be submitted at six months, and at one year and two years post-donation. Standardized data collection forms will be made available for living donor recovery hospitals to submit information voluntarily via secure email to the OPTN. The OPTN will use any information received to determine if living donors experience short-term health complications and how living donation may impact donors’ short-term quality of life. Follow-up information submitted by transplant centers is the only method currently available to obtain information on living donors. The donor hospital is strongly recommended to provide the following information:

• Patient status: alive, dead, lost to follow-up
• Cause of death if applicable and known within 72 hours if possible
• Working for income – and if not reason for not
• Whether the donor has health insurance
• Loss of medical (health, life) insurance due to donation
• Hospital readmissions and cause
• Complications related to donation

6. Medical Evaluation after Living Donation

Prior to donation, the living VCA donor should commit to post-operative follow-up testing coordinated by the recovery hospital for a minimum of two years. The recovery hospital should specify who is responsible for the cost of follow-up care related to the donation process. Given that living VCA donation is experimental and is recommended to be performed under an approved IRB protocol at the recovery hospital’s institution, if donor insurance will not cover the costs, the recovery hospital should cover any costs of follow-up care.

Following VCA living donation, the living donor should remain informed about his/her health and have basic medical evaluations performed as listed below. The living donor program should identify who will provide this follow-up.

• An age appropriate physical exam;
• Laboratory studies as indicated;
• Radiological imaging as indicated;
• Specific medical and surgical evaluation for loss of physical function or changes in physical appearance related to the VCA donation;
• Assessment for additional therapy or interventions to treat loss of function, changes in physical appearance or disability; and
• Psychological evaluation to assess donor response to changes in physical function or appearance.

All living VCA donors should be encouraged to maintain lifestyle choices that will protect their overall health, and should be advised to establish a health evaluation schedule as recommended by the American College of Physicians. However, evaluations independent of the donation process may become the financial responsibility of the living VCA donor.

7. Other Considerations

Living VCA Donor Programs should also be in compliance with other approved policies for living donation:

A. OPTN Policy 14.5 – Registration and Blood Type Verification of living Donors before Donation

• VCA is exempt from this policy requirement because living VCA donors cannot be entered on Living Donor Feedback Form. The recovery program should have a protocol to verify the living donor’s blood type as outlined in the policy.

B. OPTN Policy 14.6 – Placement of living donor organs

C. OPTN Policy 14.7 – Packaging and Labeling

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