Solid organ procurement and transplantation from deceased donors with vaccine-induced thrombosis and thrombocytopenia.
Ontology highlight
ABSTRACT:
SUBMITTER: Loupy A
PROVIDER: S-EPMC8441882 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Uterus transplantation is a surgical treatment for women with congenital or acquired uterine factor infertility. While uterus transplantation is a life-enhancing transplant that is commonly categorized as a vascular composite allograft (e.g., face or hand), it is similar to many solid organ transplants (e.g., kidney) in that both living donors (LDs) and deceased donors (DDs) can be utilized for organ procurement. While many endpoints appear to be similar for LD and DD transplants (including graft survival, time to menses, livebirth rates), there are key medical, technical, ethical, and logistical differences between these modalities. Primary considerations in favor of a LD model include thorough screening of donors, enhanced logistics, and greater donor availability. The primary consideration in favor of a DD model is the lack of physical or psychological harm to a living donor. Other important factors, that may not clearly favor one approach over the other, are important to include in discussions of LD vs. DD models. We favor a stepwise approach to uterus transplantation, one in which programs first begin with DD procurement before attempting LD procurement to maximize successful organ recovery and to minimize potential harms to a living donor.
| S-EPMC9369769 | biostudies-literature
Project description:We present a summary of the evidence on testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and organ procurement from deceased donors and provide recommendations based on current clinical data and the guidelines from major transplant organizations. Because of the limited historical experience with coronavirus disease 2019 (COVID-19), certain recommendations in this document are based on theoretical rationales rather than clinical data. The recommendations in this manuscript may be subject to revision as subsequent clinical studies provide definitive evidence regarding COVID-19 in organ procurement.
| S-EPMC10583974 | biostudies-literature
Project description:Deceased donor kidney allocation follows a ranked match-run of potential recipients. Organ procurement organizations (OPOs) are permitted to deviate from the mandated match-run in exceptional circumstances. Using match-run data for all deceased donor kidney transplants (Ktx) in the US between 2015 and 2019, we identified 1544 kidneys transplanted from 933 donors with an OPO-initiated allocation exception. Most OPOs (55/58) used this process at least once, but 3 OPOs performed 64% of the exceptions and just 2 transplant centers received 25% of allocation exception Ktx. At 2 of 3 outlier OPOs these transplants increased 136% and 141% between 2015 and 2019 compared to only a 35% increase in all Ktx. Allocation exception donors had less favorable characteristics (median KDPI 70, 41% with history of hypertension), but only 29% had KDPI ≥ 85% and the majority did not meet the traditional threshold for marginal kidneys. Allocation exception kidneys went to larger centers with higher offer acceptance ratios and to recipients with 2 fewer priority points-equivalent to 2 less years of waiting time. OPO-initiated exceptions for kidney allocation are growing increasingly frequent and more concentrated at a few outlier centers. Increasing pressure to improve organ utilization risks increasing out-of-sequence allocations, potentially exacerbating disparities in access to transplantation.
| S-EPMC9081167 | biostudies-literature
Project description:BackgroundProcurement biopsies have become a common practice in the evaluation and allocation of deceased donor kidneys in the United States despite questions about their value and reproducibility. We sought to determine the extent of OPO-level differences in criteria used to decide which deceased donor kidneys undergo a procurement biopsy and to assess the degree of variability in procurement biopsy technique and interpretation across OPOs.MethodsEach of the country's 58 OPOs were invited to participate in the survey. OPOs were divided into two groups based on organ availability ratio and deceased donor kidney discard rate.Results and conclusionsFifty-out-of-fifty-eight invited OPOs (86% response rate) responded to the survey between November 2020 and December 2020. Thirty (60%) OPOs reported that they have formal criteria for performing kidney procurement biopsy, but for 29 of these OPOs, transplant centers can request biopsy on kidneys that do not meet criteria. OPOs used a total of seven different variables and 12 different numerical thresholds to define impaired kidney function that would prompt a procurement biopsy. Additionally, wide variability was seen in biopsy technique and procedures for biopsy interpretation and reporting of findings to transplant programs. These findings identify a clear opportunity for standardization of procurement biopsies to best practices.
| S-EPMC8556234 | biostudies-literature
Project description:In the spring of 2021, reports of rare and unusual venous thrombosis in association with the ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to a brief suspension of their use by several countries. Thromboses in the cerebral and splanchnic veins among patients vaccinated in the preceding 4 weeks were described in 17 patients out of 7.98 million recipients of the Ad26.COV2.S vaccine (with 3 fatalities related to cerebral vein thrombosis) and 169 cases of cerebral vein thrombosis among 35 million ChAdOx1 recipients. Events were associated with thrombocytopenia and anti-PF4 (antibodies directed against platelet factor 4), leading to the designation vaccine-induced immune thrombotic thrombocytopenia. Unlike the related heparin-induced thrombotic thrombocytopenia, with an estimated incidence of <1:1000 patients treated with heparin, and a mortality rate of 25%, vaccine-induced immune thrombotic thrombocytopenia has been reported in 1:150 000 ChAdOx1 recipients and 1:470 000 Ad26.COV.2 recipients, with a reported mortality rate of 20% to 30%. Early recognition of this complication should prompt testing for anti-PF4 antibodies and acute treatment targeting the autoimmune and prothrombotic processes. Intravenous immunoglobulin (1 g/kg for 2 days), consideration of plasma exchange, and nonheparin anticoagulation (argatroban, fondaparinux) are recommended. In cases of cerebral vein thrombosis, one should monitor for and treat the known complications of venous congestion as they would in patients without vaccine-induced immune thrombotic thrombocytopenia. Now that the Ad26.COV2.S has been reapproved for use in several countries, it remains a critical component of our pharmacological armamentarium in stopping the spread of the human coronavirus and should be strongly recommended to patients. At this time, the patient and community-level benefits of these two adenoviral vaccines vastly outweigh the rare but serious risks of vaccination. Due to the relatively low risk of severe coronavirus disease 2019 (COVID-19) in young women (<50 years), it is reasonable to recommend an alternative vaccine if one is available. Ongoing postmarketing observational studies are important for tracking new vaccine-induced immune thrombotic thrombocytopenia cases and other rare side effects of these emergent interventions.
| S-EPMC8378439 | biostudies-literature
Project description:Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare yet serious adverse effect of the adenoviral vector vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen) against COVID-19. The mechanisms involved in clot formation and thrombocytopenia in VITT are yet to be fully determined. Here we show neutrophils undergoing NETosis and confirm expression markers of NETs in VITT patients. VITT antibodies directly stimulate neutrophils to release NETs and induce thrombus formation containing abundant platelets, neutrophils, fibrin, extracellular DNA and citrullinated histone H3 in a flow microfluidics system and in vivo. Inhibition of NETosis prevents VITT-induced thrombosis in mice but not thrombocytopenia. In contrast, in vivo blockage of FcγRIIa abrogates both thrombosis and thrombocytopenia suggesting these are distinct processes. Our findings indicate that anti-PF4 antibodies activate blood cells via FcγRIIa and are responsible for thrombosis and thrombocytopenia in VITT. Future development of NETosis and FcγRIIa inhibitors are needed to treat VITT and similar immune thrombotic thrombocytopenia conditions more effectively, leading to better patient outcomes.
| S-EPMC9441824 | biostudies-literature
Project description:Brain death-induced cytokine storm is thought to harm transplantable organs. However, longer procurement times have been associated with non-inferior or better outcomes in kidney, heart, and lung transplants, while optimal procurement time for liver allografts is unknown. Our aim was to analyze the association of time interval from brain death to organ procurement with liver allograft outcomes in two nationwide cohorts. The association of procurement interval with graft survival and short-term complications was analysed in multivariable models. Altogether 643 and 58,017 orthotopic liver transplantations from brain-dead donors were included from Finland between June 2004 and December 2017 and the US between January 2008 and August 2018, respectively. Median time from brain death to organ procurement was 10.5 h in Finland and 34.6 h in the US. Longer interval associated with better graft survival (non-linearly, p = 0.016) and less acute rejections (OR 0.935 95% CI 0.894-0.978) in the US cohort, and better early allograft function (p = 0.005; Beta -0.048 95% CI -0.085 -(-0.011)) in the Finnish cohort, in multivariable models adjusted with Donor Risk Index, recipient age, Model for End-Stage Liver Disease and indication for transplantation. Progressive liver injury after brain death is unlikely. Rushing to recover seems unnecessary; rest and repair might prove beneficial.
| S-EPMC9472133 | biostudies-literature
Project description:ObjectivesTo explore the experiences of people up to 18 months after being diagnosed with vaccine-induced immune thrombocytopenia and thrombosis (VITT).DesignA semistructured qualitative study, conducted via Zoom, of a cohort of people with VITT.SettingParticipants discussed their experiences of hospitalisation and following discharge.Participants14 individuals diagnosed with VITT, recruited via a Facebook support group and advertising on Twitter.ResultsThematic analysis identified challenges of obtaining medical care and diagnosis; fear of the severity of symptoms and unclear prognosis; and lack of family support due to isolation imposed by the COVID-19 pandemic. Once home, participants experienced continued significant symptoms; fear of recurrence; inadequate medical knowledge of their condition; and difficulties coping with residual physical disabilities and psychosocial losses. Also reported were feelings of isolation and abandonment due to lack of government support.ConclusionsThis is a significantly challenged group of people, with multiple health, financial, social and psychological losses. These losses have been compounded by experiences of limited governmental and societal recognition of the problems they face.
| S-EPMC10335444 | biostudies-literature
Project description:Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.
| S-EPMC6711782 | biostudies-literature
Project description:Use of deceased diabetic donor kidneys has increased over recent decades. However, scarce patient and allograft survival data are available taking into account recipient diabetes status. Here we performed a retrospective cohort study using data from the United Network of Organ Sharing in patients transplanted from 1994 to 2014. Multivariable Cox regression assessed recipient outcomes of 9074 diabetic vs. 152,555 non-diabetic donor kidneys. Recipients of diabetic donor kidneys had elevated rates of all-cause allograft failure (hazard ratio 1.21, 95% confidence interval 1.16-1.26) and death (1.19, 1.13-1.24) compared to recipients of kidneys from non-diabetic donors. Younger recipients of diabetic donor kidneys had worse allograft survival than older recipients of non-diabetic donor kidneys. There was significant interaction between donor and recipient diabetes status. To minimize the effect of unmeasured confounders, we used paired analyses of recipients of mate-kidneys from the same donor, with one diabetic recipient and the other non-diabetic. Among discordant recipient pairs of diabetic donor kidneys, diabetic recipients had significantly higher risk of allograft failure (1.27, 1.05-1.53) and death (1.53, 1.22-1.93) than non-diabetic recipients. After stratifying by Kidney Donor Profile Index risk category, diabetic recipients of diabetic donor kidneys continued to have worse allograft survival compared to all other patients. Thus, risks are associated with the use of diabetic donor kidneys. Understanding these risks will enable clinicians to better educate potential recipients.Kidney International advance online publication, 21 October 2015; doi:10.1038/ki.2015.325.
| S-EPMC4840104 | biostudies-literature