Developing a protocol for bloodless medicine patients undergoing transfusion-free kidney transplantation Free

Bloodless medicine patients, including Jehovah's Witnesses (JW), have provided a natural case study for examining how adjuvant therapies can improve cytopenias without red cell, plasma, or platelet transfusions. Guidelines regarding optimization for JW patients undergoing kidney transplantation (KT) are not well established, with infrequent case studies reported. We propose treatment strategies for JW patients undergoing live-donor kidney transplantation (LDKT) or deceased-donor kidney transplantation (DDKT) at our single-institution's Centre for Transfusion-Free Medicine (CTFM). Our CTFM-KT protocol targets 3 identifiable challenges: establishing pre-transplant hemoglobin (Hb) thresholds, using plasma-free INR-reversal agents for Warfarin-based anticoagulation, and managing post-transplant anemia.

Chronic dialysis patients are deemed eligible for KT when they reach an estimated glomerular filtration rate of <20ml/min. Prior evidence on JW patients undergoing KT has shown that post-transplant Hb levels drop approximately 2g/dL from pre-transplant Hb levels within 7-days, with a mean pre-transplant Hb level of 12.9g/dL (Carvalho Fiel et al., 2021). Our CTFM data on JW patients undergoing autologous stem cell transplantation (ASCT) has shown success with pre-transplant Hb levels as low as 9.7g/dL (Patel et al., 2024). Thus, using our CTFM's pre-established protocols for bloodless ASCT and cardiovascular surgery in congruence with KDIGO guidelines, our patients will be maintained at a pre-operative Hb threshold of >11g/dL. Pre-transplant optimization strategies will include using short-acting erythropoietin-stimulating agents (ESAs) thrice weekly with dialysis, intravenous iron, and nutritional assessments. Oftentimes, KT-eligible patients requiring direct oral anticoagulation are preferably switched to alternative agents like Warfarin (Vitamin K Antagonist – VKA) per KDIGO practice guidelines. At our single-institution, the routine use of fresh frozen plasma (FFP) for INR-reversal in patients on Warfarin immediately excludes potential JW patients awaiting KT. Thus, for anticoagulation reversal, we propose the use of fractionated, 4-factor prothrombin complex concentrate (4F-PCC) in lieu of FFP as an acceptable alternative for JW patients prior to KT if they are to continue a VKA. The use of 4F-PCC in urgent surgical or invasive procedures has been proven to be superior and non-inferior to plasma, due to its lower post-transfusion volume burden and lower risk of ABO-incompatibility (Goldstein et al., 2015). In the setting of rapid reversal, 4F-PCC is dosed by body-weight and renal function to achieve pre-transplant hemostasis. Following optimization of pre-transplant Hb levels and adequate INR-management with plasma-sparing agents and VKAs, transplant surgeons further consider specific intra-operative surgical techniques to minimize blood loss as part of routine blood-management care. Prior evidence on dual-organ (pancreas-kidney) transplantation has continually advocated for the use of cell-savers to preserve autologous blood (Figueiro et al., 2003). Similar blood-sparing techniques exist in studies with bloodless kidney donations, where specific laparoscopic incisions, acute normovolemic hemodilution, and hand assistance were employed to minimize intra-operative and iatrogenic blood loss (Mateo et al., 2007). Finally, through early multi-disciplinary evaluation, post-transplant anemia will be managed collaboratively under the guidance of transplant nephrology, hematology, and when required, infectious diseases. Historically, bloodless-KT patients who develop severe anemia post-transplant, whether it be through hemorrhage, drug-toxicity, or hemolysis, have been associated with higher fatality rates if they subsequently developed delayed graft function, compared to patients without severe anemia (Kaufman et al., 1988).

Our CFTM protocol emphasizes blood-management concepts using prior data on ASCTs and cardiovascular surgery to allow JW populations to be considered for LDKT and DDKT at our institution. By creating a pre-operative Hb threshold, offering plasma-free alternative agents for anticoagulation reversal, and holistic evaluation with multi-disciplinary involvement, our CFTM will be able to collect longitudinal data on clinical outcomes of JW patients undergoing KT to increase the accessibility of a life-prolonging procedure.