Impact of early corticosteroid withdrawal on simultaneous pancreas-kidney transplant long-term outcomes: Single center experience and comparison to the International Pancreas Transplant Registry.

BACKGROUND: There remains a paucity of modern data comparing early steroid withdrawal (ESW) versus chronic corticosteroid (CCS) immunosuppression in simultaneous pancreas kidney (SPK) transplant recipients with long-term follow-up. Therefore, the purpose of this study is to assess the effectiveness and tolerability of ESW compared to CCS post-SPK. METHODS: This was a retrospective single-center matched comparison with the International Pancreas Transplant Registry (IPTR). Patients from University of Illinois Hospital (UIH) represented the ESW group and were compared to those matched CCS patients from the IPTR. Included patients were adult recipients of a primary SPK transplant between 2003 and 2018 within the US receiving rabbit anti-thymocyte globulin induction. Patients were excluded if they had early technical failures, missing IPTR data, graft thrombosis, re-transplant, or positive crossmatch SPK. RESULTS: A total of 156 patients were matched and included in the analysis. Patients were predominantly African American (46.15%) males (64.1%) with Type 1 diabetes etiology (92.31%). Overall pancreas allograft survival (hazard ratio [HR] = .89, 95% confidence interval [CI] .34-2.30, p = .81) and kidney allograft survival (HR = .80, 95%CI .32-2.03, p = .64) were similar between the two groups. Immunologic pancreas allograft loss was statistically similar at 1-year (ESW 1.3% vs. CCS 0%, p = .16), 5-year (ESW 1.3% vs. CCS 7.7%, p = .16), and 10-year (ESW 11.0% vs. CCS 7.7%, p = .99). The 1-year (ESW 2.6% vs. CCS 0%, p > .05), 5-year (ESW 8.3% vs. CCS 7.0%, p > .05), and 10-year (ESW 22.7% vs. CCS 9.9%, p = .2575) immunologic kidney allograft loss were also statistically similar. There was no difference in 10-year overall patient survival (ESW 76.2% vs. CCS 65.6%, p = .63). CONCLUSIONS: No differences were found between allograft or patient survival post-SPK when comparing an ESW or CCS protocol. Future assessment is needed to determine differences in metabolic outcomes.

A systematic review of opioid use and multimodal strategies in solid organ transplant recipients and living donors.

The opioid epidemic has impacted analgesia in the postoperative period for solid organ transplant (SOT) donors and recipients. However, optimal pain management and opioid stewardship strategies have not been identified across this unique population. The purpose of this systematic review was to evaluate the impact of perioperative opioid use and to describe multimodal analgesic strategies to reduce opiate use in SOT recipients and living donors. A systematic review was conducted. Electronic searches were performed in Medline, Embase, Google Scholar, and Web of Science through December 31, 2021. Title and abstracts were screened. Relevant articles underwent full-text review. Literature was separated into effects of opioid exposure on post-transplant outcomes, recipient pain management strategies, and living donor pain management strategies. Search yielded 25,190 records, and 63 were ultimately included. The impact of opioid use on post-transplant outcomes was assessed in 19 publications. The risk of graft loss in pretransplant opioid users was assessed in six reports and was found to be higher in the majority (66%) of publications. Opioid minimization strategies were reported in 20 studies in transplant recipients. Twenty-four studies evaluated pain management strategies in living donors. Both populations used a combination of multimodal strategies to minimize opioid use throughout the hospitalization and on discharge. Opioids are associated with select negative outcomes in post-transplant recipients. To minimize their use while also maintaining appropriate analgesia, multimodal pain regimens should be considered in SOT recipients and donors.

The expanded role of the transplant pharmacist: A 10-year follow-up.

The role of the transplant pharmacist is recognized by transplant programs, governmental groups, and professional organizations as an essential part of the transplant multidisciplinary team. This role has evolved drastically over the last decade with the advent of major advances in the science of transplantation and the growth of the field, which necessitate expanded pharmacy services to meet the needs of patients. Data now exist within all realms of the phases of care for a transplant recipient regarding the utility and benefit of a solid organ transplant (SOT) pharmacist. Furthermore, governing bodies now have the opportunity to use Board Certification in Solid Organ Transplant Pharmacotherapy as a mechanism to identify and recognize specialty knowledge and expertise within the field of SOT pharmacotherapy. The purpose of this paper is to provide an overarching review of the current and future state of SOT pharmacy while also identifying major changes to the profession, forthcoming challenges, and expected areas of growth.

Evaluating the Incidence and Risk Factors for Acute Cellular Rejection in a Steroid Sparing Liver Transplant Center.

BACKGROUND: Corticosteroids has been the mainstay of immunosuppression (IMS) following liver transplant (LT). With the advent of more potent IMS, complete steroid withdrawal has become possible after LT. However, there is limited data regarding the incidence and risk factors for acute cellular rejection (ACR) in LT recipients on steroid sparing regimens. OBJECTIVE: To identify the incidence and risk factors of ACR in LT recipients at an urban LT center utilizing a steroid-sparing IMS regimen. METHODS: This was a single center retrospective study evaluating incidence of ACR in adults (>18 years) who received a LT between 01/01/2008 and 6/30/2019 at a steroid-sparing liver transplant center. Data between patients who had ACR and patients who did not were compared and risk factors were identified by multivariate logistic linear regression. RESULTS: A total of 266 patients were included in this analysis, of which 18.4% experienced ACR within the first year of LT. Median time to first ACR was 134 (interquartile range [IQR]: 34-246) days. Black race (odds ratio [OR]: 4.39, P < 0.001), continued need for prednisone (OR: 2.80, P = 0.015) and cytomegalovirus (CMV) viremia (OR: 6.27, P < 0.001)) were independent risk factors for ACR. Tacrolimus use was associated with less ACR (OR: 0.33, P = 0.013). CONCLUSION AND RELEVANCE: Steroid sparing regimens for IMS post-LT were not associated with an increased incidence of ACR when compared to reported ACR rates in literature. Potential risk factors for ACR include Black race, the use of prednisone maintenance IMS therapy, and CMV viremia.

Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation.

BACKGROUND: Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation. AIMS: Characterize associations between gut microbiome features and pain interference before and after kidney transplantation. DESIGN: Longitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant. SETTING: Participants were recruited at the kidney transplant clinic at the University of Illinois Hospital & Health Sciences System. PARTICIPANTS/SUBJECTS: 19 living donor kidney transplant recipients. METHODS: We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57. RESULTS: We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R = .306, p = .022), and between pain interference groups at posttransplant (R = .249, p = .041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene. CONCLUSIONS: Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.

The utilization and safety of apixaban for therapeutic anticoagulation in heart transplant population requiring routine endomyocardial biopsies.

PURPOSE: Routine endomyocardial (EM) biopsies pose a challenge in the management of heart transplant recipients requiring anticoagulation. Apixaban is a direct-acting oral anticoagulant (DOAC) with a short half-life allowing for brief interruptions of anticoagulation for procedures. The study objective was to determine the safety and efficacy of apixaban in heart transplant patients undergoing EM biopsies. METHODS: This retrospective case series evaluated patients with a heart transplant from April 1, 2017 to July 30, 2020 who were treated with apixaban within 90 days post-transplant. The primary outcome was the occurrence of a bleeding or thrombotic event. RESULTS: A total of 12 patients with >100 biopsies were included. The median age was 54 years (IQR 37-59) with a mean weight of 91 ± 20 kg. There were no bleeding or thrombotic events. During therapy, patients underwent an average of eight biopsies. The median time from transplant to initiation of apixaban was 39.5 days (range 9-77). Therapy was maintained without any need for reversal for a median of 276 days (IQR 45-245). CONCLUSIONS: Apixaban is safe to use for anticoagulation of heart transplant recipients undergoing routine biopsies. Using apixaban allows for a short interruption of therapeutic anticoagulation to accommodate a biopsy without increased risk of bleeding.

Incidence and risk factors for the development of cytomegalovirus viremia in a steroid sparing liver transplant center.

BACKGROUND: Cytomegalovirus (CMV) is a common opportunistic infection in patients after liver transplant (LT). Guidelines recommend 900 mg daily of valganciclovir; however, valganciclovir commonly causes dose-dependent hematologic toxicities. Use of a low-dose valganciclovir (450 mg) has been used to prevent these adverse effects, but the data regarding this dosing strategy are not as robust in a steroid sparing LT center. METHODS: Retrospective chart review of adult LT recipients between January 1, 2008 and June 30, 2019. All patients received low-dose valganciclovir 450 mg PO daily for CMV prophylaxis. Primary outcome was the incidence of CMV viremia in LT recipients at 12 months post-LT. Secondary outcomes include time to CMV viremia, risk factors for the development of CMV viremia, and incidence of breakthrough CMV viremia while on valganciclovir prophylaxis. RESULTS: A total of 266 patients were included. Overall, the majority were male (63.2%) and Caucasian (45.5%). The most common indication for transplant was decompensated cirrhosis (82%). The incidence of CMV at 1 year posttransplant was 7.9%. Independent risk factors included high risk status (OR 5.97, 95% CI 2.14-16.61, p = .001) as well as having an episode of rejection (OR 5.99, 95% CI 2.16-16.66, p = .001). CONCLUSION: Low-dose valganciclovir can be effective in the prevention of CMV viremia in LT patients and may be a beneficial strategy for CMV prophylaxis in a steroid-sparing transplant center. Further studies may be needed to determine appropriate length of prophylaxis therapy for different risk groups.

Assessment of the prevalence of burnout and well-being in solid organ transplant pharmacists.

BACKGROUND: Solid organ transplant (SOT) pharmacist burnout and well-being has not been described. METHODS: A survey of SOT pharmacists was distributed to transplant pharmacy organization listservs. Burnout was assessed with the full 22 item Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSS-MP) and well-being was assessed with the Mayo Well-Being Index (WBI). Logistic multivariate regression was constructed to identify risk factors for a composite burnout assessment. RESULTS: In total, 230 responses were included (estimated response rate 36.2%). Survey participants were predominantly Caucasian (80.4%), female (79.1%), married/partnered (67.4%), and were within the first 5 years of practice (32.2%) as clinical pharmacist/specialists (87%). According to the MBI-HSS-MP, 63% met criteria for burnout. Comparing the groups with or without burnout, low quality of life (40.4% vs. 9.5%; P<.001), extreme fatigue (52.1% vs. 19%; P<.001), and likelihood of leaving the job for reasons other than retirement (38.5% vs. 10.7%; P<.001) were more common. The incidence of SOT pharmacists with WBI scores ≥ 5 (decreased well-being) was 26.5%. Among clinical pharmacists, risk factors for burnout included > 10 h per week of clinical duties outside of transplant (OR 2.669, P = .021) and extreme fatigue (OR 3.473, P<.001). CONCLUSIONS: Pharmacist burnout in SOT practice was similar to that reported in various pharmacy specialties (53-61%), which impacts clinical workforce retention and personal well-being.

Perioperative Vasopressors are Associated with Delayed Graft Function in Kidney Transplant Recipients in a Primarily Black and Hispanic Cohort.

Introduction: Negative outcome studies of vasopressors in kidney transplant have not focused on patient populations that are predominantly Black or Hispanic. Project Aims: The evaluation sought to investigate the independent impact of perioperative vasopressors on postoperative renal allograft function in a sample drawn from a primarily Black and Hispanic population. Design: Retrospective, observational, single-center evaluation of patients > 18 years old who underwent kidney transplantation comparing outcomes based on vasopressor exposure. Results: The study included 150 patients of which 60 received vasopressors. The primary outcome differed between groups with delayed graft function occurring in 17(28%) versus 11(12.2%) occurring more often in those that received perioperative vasopressors (P = 0.02). The serum creatinine at postoperative day 7 was higher (2.69 vs1.52 mg/dL, P = 0.004), postoperative day 7 eGFR was worse (27.3 vs 52.9 mL/min/1.73m2, P = 0.002) in patients who received vasopressors. Patients who received perioperative vasopressors experienced more postoperative arrhythmias (15% vs 8%, P = 0.007), insulin infusion therapy (26.7% vs 13.3%, P = 0.04), and increased hospital length of stay (6 days vs 5 days, P = 0.006). Using IPWRA, patients receiving vasopressors were more likely to experience delayed function, relative risk difference of 22% (95% CI:0.08-0.35;P = 0.002) and in multivariate logistic regression modeling, an increased odds ratio of 3.2 (95% CI:1.1-8.62;P = 0.022). Conclusions: The use of perioperative vasopressors was independently associated with worsened early renal allograft function including delayed graft function, increased adverse events such as postoperative arrhythmias, and longer ICU length of stay. Further investigation is needed surrounding vasopressor use in this population.

Temporary Deceased Donor Splenic Transplant Prior to Intestinal Transplantation: A New Strategy for Desensitization?

Intestinal transplantation is a therapeutic treatment option for patients with irreversible intestinal failure. The presence of donor-specific antibodies (DSAs) has been associated with increased antibody-mediated rejection and allograft loss for recipients of all the solid organ transplants. This case report describes the posttransplant course in the first year of a patient who received a T-cell and B-cell flow cross-match (FXM) and complement-dependent cytotoxicity cross-match positive intestinal transplant in the presence of several class I and class II DSAs who underwent a "temporary desensitization" using the donor spleen. The temporary donor splenic transplant removed several class I and II DSAs as demonstrated by the negative subsequent T-cell FXM, the decreased mean channel shift of the positive B-cell FXM with a significant decrease in DSA mean florescence intensity post temporary splenic transplant. The patient experienced an isolated incidence of acute rejection, which responded to therapy. He had no infectious or cancerous sequelae from the immunosuppression modalities. He was able to discontinue total parenteral nutrition and gained weight after the procedure. Long-term effects are not able to be determined from this approach; hence, further research is warranted to better evaluate the real efficacy of this strategy.

Entrustable professional activities for pharmacy students: A primer for solid organ transplant preceptors.

DISCLAIMER: In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The role of a solid organ transplant pharmacist is multifaceted and translates to diverse experiential and elective learning experiences that can be provided to pharmacy learners. Here we provide a guide to integrating pharmacy students into patient care and other pharmacist activities in solid organ transplantation. SUMMARY: Thoughtful incorporation of learners into clinical practice and clinical research creates a positive learning environment for pharmacy students that can foster the development of core skills necessary for students to become "practice-ready" and "team-ready" pharmacy graduates and can equip them with valuable skills to incorporate into the specialty practice areas and careers they pursue. To help develop these educational experiences, attention to the list of core entrustable professional activities (EPAs) established by the American Association of Colleges of Pharmacy can help create a rich environment of learning with carefully cultivated tasks. Furthermore, learners can serve as transplant pharmacist extenders to assist in overall patient care and multidisciplinary involvement on the transplant team. This article serves as a "how-to" guide for applying the EPA framework to integrating pharmacy students in patient care and other pharmacist activities in solid organ transplantation and other specialty practice areas. CONCLUSION: As pharmacy preceptors design and operationalize their teaching to incorporate EPAs, they can benefit from recommendations tailored to specialty practice areas such as solid organ transplantation. Students may start and finish these experiences at different EPA levels, but continuance of training will allow them to achieve the final EPA level across the 6 EPA domains.

Clinical Implications of Tacrolimus Time in Therapeutic Range and Intrapatient Variability in Urban Renal Transplant Recipients Undergoing Early Corticosteroid Withdrawal.

Tacrolimus demonstrates wide intrapatient and interpatient variability requiring therapeutic drug monitoring. The utility of tacrolimus time in therapeutic range (TTR) after renal transplantation (RT) under an early corticosteroid withdrawal (ECSWD) protocol is unknown. The purpose of this study is to assess the impact of tacrolimus TTR in an ECSWD RT population. MATERIALS: A retrospective analysis of adult RT recipients maintained on tacrolimus was conducted. Patients were excluded if they were on nonstandard protocol immunosuppression agents <12 months post-RT. Tacrolimus TTR was calculated using the Rosendaal method. Patients were divided into high (TTR-H) and low (TTR-L) TTR groups based on cohort median. The primary outcome was to compare the incidence of acute rejection 12 months post-RT. Secondary outcomes included comparing rejection subtypes, incidence of donor-specific antibody (DSA) and de novo DSA (dnDSA), risk factors for acute rejection and dnDSA development, and allograft function (serum creatinine and estimated glomerular filtration rate). RESULTS: A total of 193 patients were analyzed (TTR-H = 98 and TTR-L = 95). There was no difference in the incidence of acute rejection (TTR-H 20.4% versus TTR-L 20.0%; P = 0.944). Positive DSA posttransplant (odds ratio [OR], 3.62; 95% confidence interval [CI], 1.41-9.26; P = 0.007) was associated with a higher acute rejection at 12 months posttransplant. Mycophenolate dose reduction (OR, 2.82; 95% CI, 1.13-6.97; P = 0.025) and acute rejection (OR, 2.99; 95% CI, 1.09-8.18; P = 0.032) were associated with dnDSA formation. No difference in serum creatinine or estimated glomerular filtration rate was observed (P > 0.05). CONCLUSIONS: Tacrolimus TTR was not significantly different with regards to acute rejection in an ECSWD population. Future studies are still needed to determine tacrolimus TTR thresholds post-RT and identify populations that may benefit from this intrapatient variability monitoring parameter.

A call for transplant stewardship: The need for expanded evidence-based evaluation of induction and biologic-based cost-saving strategies in kidney transplantation and beyond.

Rising expenditures threaten healthcare sustainability. While transplant programs are typically considered profitable, transplant medications are expensive and frequently targeted for cost savings. This review aims to summarize available literature supporting cost-containment strategies used in solid organ transplant. Despite widespread use of these tactics, we found the available evidence to be fairly low quality. Strategies mainly focus on induction, particularly rabbit antithymocyte globulin (rATG), given its significant cost and the lack of consensus surrounding dosing. While there is higher-quality evidence for high single-dose rATG, and dose-rounding protocols to reduce waste are likely low risk, more aggressive strategies, such as dosing rATG by CD3+ target-attainment or on ideal-body-weight, have less robust support and did not always attain similar efficacy outcomes. Extrapolation of induction dosing strategies to rejection treatment is not supported by any currently available literature. Cost-saving strategies for supportive therapies, such as IVIG and rituximab also have minimal literature support. Deferral of high-cost agents to the outpatient arena is associated with minimal risk and increases reimbursement, although may increase complexity and cost-burden for patients and infusion centers. The available evidence highlights the need for evaluation of unique patient-specific clinical scenarios and optimization of therapies, rather than simple blanket application of cost-saving initiatives in the transplant population.

Histopathology of Human Donor Spleen Utilized as a Desensitization Tool Before Intestinal Transplantation.

OBJECTIVES: To describe the histopathologic and immunophenotypic features of a temporary splenic allograft exposed to massive donor-specific antibody (DSA) insult. METHODS: A human cadaveric donor splenic allograft was temporarily transplanted in a highly sensitized patient with the intention of removing DSA before intestinal transplantation from the same donor. Before splenic transplant, the patient had several preformed cytotoxic DSAs that resulted in positive flow cytometric and complement-dependent cytotoxicity crossmatch. The splenic allograft was removed before intestinal transplantation and evaluated by H&E and immunohistochemical stains. RESULTS: Explanted donor splenic allograft showed several histopathologic changes: expanded red pulp secondary to congestion and marked neutrophilic and macrophage infiltration in the sinusoids, numerous neutrophilic microabscesses, and focal capillaritis. The C4d and IgG immunohistochemical stains were diffusely positive in the endothelial lining of the capillaries and sinusoidal lining, indicating diffuse IgG deposition and complement activation. CONCLUSIONS: We propose that the noted changes are features of splenic acute antibody-mediated rejection (AMR). Additional cases are required to determine all the features of splenic AMR. To our knowledge, this is the first report of histopathologic changes in donor spleen after exposure to DSA for a short duration.

Factors Influencing Emergency Department Utilization and Hospital Re-Admissions in a Predominantly Obese, Racially Diverse Urban Renal Transplant Population.

INTRODUCTION: Early emergency department and hospital re-admissions are common in renal transplant recipients, but data are lacking in unique populations. Study Aim: The purpose of this study was to identify patient risk factors for multiple acute care utilization events within the first year of renal transplantation. DESIGN: This was a single-center, retrospective cohort study of adult renal transplant recipients between 9/2013-9/2016. Patients were compared across number of emergency department visits and by hospital re-admissions. Diagnoses were categorized. Univariate and multivariate logistic regression was used to assess risk for multiple acute care utilization events within the first 12 months post-transplant. RESULTS: A total of 216 patients were analyzed and were on average 50.5 (SD 13.9) years old, redominantly Black (49.77%) with an average body mass index of 33.33 (9.8) and were recipients of deceased donor renal transplants (61.11%). A total of 105 (48.6%) patients visited the emergency epartment and 119 (55.1%) patients had a hospital readmission. Patients having a body mass index >35 kg/m2 did not differ across emergency department visit or hospitalization groups. Delayed graft function (OR 2.86, 95% CI 1.07-7.65) and previous renal transplant (OR 2.77, 95% CI 1.04-7.39) were significantly associated with multiple acute care utilizations. DISCUSSION: Acute care utilization following renal transplantation was similar to previously reported experiences. Obesity did not impact use of acute care resources or patient outcomes. Strategies addressing potential preventable emergency visits and hospital re-dmissions should be promoted.

The Significance and Impact of Screening Preservation Fluid Cultures in Renal Transplant Recipients.

INTRODUCTION: Infectious complications can be a major cause of morbidity and mortality in solid organ transplant recipients. Preservation fluid is necessary to maintain organ viability but may serve as a vector or infection. The utility of screening preservation fluid routinely for microbial growth and the impact of culture-positive preservation fluid is controversial. Research Question: What is the clinical impact of a culture positive preservation fluid in a kidney transplant recipient? DESIGN: This retrospective study was performed to define the incidence of post-operative infection related to PF and examine the negative sequelae of culture-positive PF. One hundred and fifty-two deceased donor renal transplant recipients from January 2015 to December 2017 were included for analysis. RESULTS: Overall, 67% of patients (102/152) received an allograft from a culture-positive PF. Nearly 80% of microbial growth was consistent with skin flora, and coagulase-negative staphylococci was the most frequently isolated organism (56%). Sixty-seven percent of patients (68/102) with culture-positive PF received antimicrobial treatment for an average duration of 5 days. There was no difference in the incidence of infection between patients with culture positive PF compared to culture-negative PF. Furthermore, there were no cases of infection related to PF regardless of whether culture-positive PF was treated or untreated. The incidence of subsequent C. difficile infection and multidrug-resistant organisms was similar. DISCUSSION: This study suggests antimicrobial treatment for culture positive PF may not be necessary with pathogens that are common contaminants and of low virulence. Interventional studies are needed to validate this strategy.

Use of direct-acting oral anticoagulants in solid organ transplantation: A systematic review.

The use of direct-acting oral anticoagulants (DOACs) has increased secondary to the mounting evidence for comparable efficacy and potentially superior safety to vitamin K antagonists (VKAs) in the general population. However, insufficient data regarding DOAC use in solid organ transplant (SOT) recipients and numerous pharmacokinetic and pharmacodynamic considerations limit their use in this highly selected patient population. A systematic review of recent clinical evidence on the safety and efficacy of DOACs compared to VKAs in SOT recipients was conducted. Additional considerations including transplant-specific strategies for DOAC reversal and common pharmacokinetic/pharmacodynamic concerns were also reviewed. Although current evidence is limited to single-center retrospective analyses, DOACs, especially apixaban, appear to be a safe and effective alternative to VKAs for SOT recipients with stable graft function and without drug-drug interactions. Reliable data on DOAC reversal at the time of transplant surgery are lacking, and clinicians should consider idarucizumab, andexanet alfa, and other non-specific reversal agents on an individual patient basis. There is no evidence supporting deviations from the Food and Drug Administration labeling recommendations for DOAC dosing in the setting of drug-drug interactions, obesity, and renal function, especially in patients on hemodialysis.

Utilization of direct-acting oral anticoagulation in solid organ transplant patients: A national survey of institutional practices.

The safety and efficacy of direct-acting oral anticoagulants (DOACs) and reversal strategies are not well established in the solid organ transplant population. This was a survey of pharmacists to assess DOAC and urgent reversal practices among adult transplant programs in the United States. A 27-question survey was distributed to members of transplant pharmacy organization listservs between 5/28/19 and 6/30/19. A total of 115 responses were received from kidney (43.5%), heart (20.0%), lung (18.3%), liver (13.9%), and pancreas (4.4%) transplant programs. DOAC use prior to transplant was mostly prohibited in thoracic programs (77.3%) but more permissive in kidney transplant programs (64.0%). If permitted, apixaban (57.8%) was most preferred. At transplant surgery, reversal of DOAC was performed "as needed" (20.9%) or was not routine (18.3%). DOAC use post-transplant was more permissive (94.3%). A majority of responders follow FDA recommended dosing in the setting of drug-drug interactions (51.1%). Major factors influencing DOAC prescribing decisions included renal function, drug-drug interactions, and insurance. High clinical practice variability exists regarding DOAC utilization and urgent reversal strategies in pre-, peri-, and post-transplant stages. While more research is needed to refine the clinical landscape, many institutions are using DOAC therapy under the perception that they pose a similar risk of bleeding compared to a non-transplant population.