The haematological features and transfusion management of women who required massive transfusion for major obstetric haemorrhage in the UK: a population based study.

Understanding the coagulopathy of major-obstetric-haemorrhage (MOH) that leads to massive-transfusion (MT) is fundamental to improving outcomes. This study reports on the haematological features and transfusion management of women experiencing MT [defined as transfusion of ≥8 units of red blood cells (RBC) within 24 h of delivery]. One hundred and eighty-one cases [median (interquartile range; IQR) age 33 years (29-36)] were identified from all UK hospitals, using the UK Obstetric Surveillance System between July 2012 and June 2013. The median (IQR) estimated blood loss was 6 l (4·5-8). At presentation, the median platelet count was lowest for placenta accreta, compared with other causes, while the median prothrombin time and fibrinogen were <1·5 × mean normal and <3 g/l, respectively for all aetiologies. Median platelet count and fibrinogen fell to <75 × 10(9) /l and <2 g/l, respectively for all causes during bleeding, except for trauma. The median (IQR) units of RBC, fresh-frozen-plasma (FFP) and cryoprecipitate transfused were 10 (8-14), 6 (4-8) and 2 (2-4), respectively. The median time from the onset of bleeding to delivery of the first RBC unit was significantly shorter for women who delivered via elective caesarean section, compared with others. The coagulopathy of MT during MOH differs significantly depending on its cause, suggesting that more targeted transfusion strategies are required.

Where do all the red blood cells (RBCs) go? Results of a survey of RBC use in England and North Wales in 2014.

BACKGROUND: Knowledge of blood utilization can assist clinicians in directing patient blood management (PBM) initiatives and can facilitate demand planning by blood services. We describe a national study of red blood cell (RBC) utilization in England and North Wales in 2014. STUDY DESIGN AND METHODS: All hospitals that are supplied with blood components by NHS Blood and Transplant (NHSBT) were asked to provide data on the age and sex of all recipients of transfusions of RBCs, and the clinical indication for every unit transfused, for two separate weeks in 2014. Clinical indication categories were derived from those used in previous studies in an English region. Completeness of data collection was checked against NHSBT issue and wastage data. RESULTS: Data on 46,111 RBC units were collected, representing 73% of all RBCs issued by NHSBT during the weeks surveyed. A total of 67% of RBC units were transfused for a medical indication, with 27 and 6% being transfused for surgical and obstetric/gynecologic indications, respectively. For comparison, figures from a study in the North of England in 2009, on which this national study was based, showed that 64% of RBCs were transfused to medical patients. All but 20 units could be ascribed to a broad clinical heading, for example, "gastrointestinal bleeding." CONCLUSION: Our findings confirm the previous regional finding that the percentage of RBC units that are transfused to surgical patients in England and North Wales is now much lower than for medical patients and suggest that PBM initiatives should now focus on medical patients.

Influence of surgeon learning on outcomes in new ophthalmic procedures: quantified nationwide evidence in endothelial corneal transplantation.

AIMS: To investigate the impact of surgeon learning on endothelial keratoplasty (EK) procedure outcomes. METHODS: A prospective nationwide registry study of EK grafts in patients aged at least 21 years with Fuchs endothelial corneal dystrophy or pseudophakic bullous keratopathy undergoing a first EK procedure in that eye between 2005 and 2020. EK procedures were either Descemet Stripping Endothelial Keratoplasty (DSEK) or Descemet Membrane Endothelial Keratoplasty (DMEK). Primary outcome was transplant survival at 2 years. Secondary outcomes at 1-year post-transplant were (1) best-corrected visual acuity, (2) requirement for repeat air injection procedures to treat graft detachment and (3) iatrogenic primary graft failure. RESULTS: Following analysis of 11 516 EK transplants, significant impact of surgeon learning was indicated by (1) the influence of surgeon prior experience in that EK technique, (2) the influence of surgeon prior experience in postoperative management and (3) the time interval from introduction of that EK technique in the United Kingdom to time of surgery. EK grafts reported to have failed within the first 6 months were a significant proportion of all transplant failures. CONCLUSIONS: Influence of surgeon learning and inexperience in EK of clinical and statistical significance can be quantified and diminishes over time. Equivalent analyses may be feasible for novel procedures in other ophthalmology specialties and surgical training. Training programmes and nationwide advisory networks may be helpful in reducing the duration and impact of surgeon learning curves.

Graphical comparison of surgeon outcomes for the audit of a national corneal transplant registry (OTAG study 32).

PURPOSE: To compare Kaplan-Meier survival curves and funnel plots for the audit of surgeon-specific corneal transplantation outcomes. METHODS: We obtained data on all patients with Fuchs endothelial dystrophy (FED) receiving a first corneal transplant in one eye between January 2012 and December 2017. We produced 2-year Kaplan-Meier graft survival curves to compare a simulated individual surgeon's graft survival rate to national pooled data. We used funnel plots to compare all surgeon outcomes to the national graft survival rate with superimposed 95 and 99.8% confidence limits. We defined an outlier as a surgeon who performed ≥10 transplants and had graft survival below the 99.8% national lower limit. To assess the effect of the surgeon case mix, we also compared unadjusted and risk-adjusted graft survival rates. RESULTS: There were 3616 first corneal transplants for FED patients with complete data, performed or overseen by 196 surgeons. The 2-year national graft survival rate was 88%. The median change from the unadjusted to the risk-adjusted graft survival rate for individual surgeons was 0% (IQR: 0%- -2%). Of the 108 surgeons who had performed ≥10 transplants, we identified two outliers based on the unadjusted graft survival funnel plot, compared to four outliers based on the risk-adjusted graft survival funnel plot. CONCLUSION: Funnel plots provide a visually accessible method for comparing individual graft survival rates to the national rate. Risk-adjustment accounts for clinical factors, and this has advantages for audit and clinical governance.

6†The impact of COVID-19 on corneal transplantation in England.

INTRODUCTION/BACKGROUND: At the beginning of the COVID-19 pandemic, eye banks around the world had to assess the impact of SARS-CoV-2 infection in potential ocular tissue donors and decide how to characterise donors to meet ongoing demand for tissue for transplantation.NHSBT eye banks normally issue cornea grafts for over 4000 transplants per annum (pre-pandemic). SARS-CoV2 RNA screening is not a requirement for eye donor characterisation. Donor authorisation is based on review of donor medical and contact history and any available COVID test results (e.g. from hospital testing or as part of organ donor characterisation). After retrieval, globes are disinfected with PVP-iodine, and corneas stored in organ culture.This presentation explores the impact of COVID-19 on corneal donation and transplantation in England. METHODS: UK Transplant Registry data were analysed on all corneal donors and transplants in England from 1 January 2020 to 2 July 2021. All laboratory confirmed SARS CoV-2 infections were collected by Public Health England from 16 March 2020. Information was available until mid-November 2021.To assess the possibility of transmission through a transplanted graft, cases with a diagnosis of infection within 14 days post transplant were identified for further review. RESULTS: 4130 corneal grafts were performed in England. We are aware of 222 recipients who tested positive for SARS-CoV2. 2 of these have been reported to have died within 28 days of testing positive. The diagnosis of SARS-CoV2 infection in these 2 recipients had been made beyond 30 days post transplant.In 3 of the 222 infected recipients, the interval between transplant and infection was within 14 days (all 3 recipients alive). 2 of the 3 donors were fully characterised organ donors (universally screened for SARS-CoV-2 RNA in upper and lower respiratory tract samples), and one was an eye only donor who had tested negative in hospital 2 days prior to death. CONCLUSIONS: The linkage of large registries allows collection of useful data in a large cohort of patients transplanted during the COVID-19 pandemic. The incidence of COVID-19 and characteristics of corneal transplant recipients who tested positive for SARS-CoV2 were found to be similar to those for the general population of England.These data have not identified any epidemiological evidence for transmission of COVID-19 through corneal transplantation, and offer reassurance about the safety and quality systems that are in place to allow ongoing corneal transplantation during the pandemic.

Endothelial failure and rejection in recipients of corneas from the same donor.

OBJECTIVE: To determine whether patients who receive corneas from the same donor have similar risks of endothelial failure and rejection. METHODS AND ANALYSIS: Patients with Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) who received their first corneal transplant between 1999 and 2016 were analysed. Patients receiving corneas from donors who donated both corneas for the same indication were defined as 'paired'. Gray's test was used to compare the cumulative incidence of endothelial failure and rejection within 5 years post-transplant for 'paired' and 'unpaired' groups. Cox regression models were fitted to determine whether there was an association between recorded donor characteristics (endothelial cell density (ECD), age and sex and endothelial graft failure and rejection. RESULTS: 10 838 patients were analysed of whom 1536 (14%) were paired. The unpaired group comprised 1837 (69%) recipients of single corneal donors and 7465 (69%) donors who donated both corneas for another indication. ECD was lower for unpaired single cornea donors (p<0.01). There was no significant difference in endothelial graft failure or rejection between paired and unpaired groups for FED (p=0.37, p=0.99) or PBK (p=0.88, p=0.28) nor for donor ECD, age, sex and paired donation after adjusting for transplant factors (across all models p>0.16 for ECD, p>0.32 for donor age, p>0.14 for sex match and p>0.17 for the donor effect). CONCLUSION: The absence of a significant difference in graft outcome for corneal transplants for FED and PBK between paired and unpaired donors may reflect a homogeneous donor pool in the UK.

Keratoplasty for Keratoconus in Young Patients: Demographics, Clinical Features, and Post-transplant Outcomes.

PURPOSE: To examine pretransplant findings and outcomes of corneal transplants for keratoconus in children. DESIGN: Retrospective cohort (national registry) study. METHODS: Data on all patients aged 16 or younger (n = 170) who had a first transplant for keratoconus between 2003 and 2018 in all corneal transplant centers in the UK were compared to adult patients aged 17 and older (n = 7,191). The influence of demographic variables, pretransplant corneal findings, and transplant type on 2-year visual, rejection-free, and transplant survival outcomes was examined. RESULTS: Children had poorer pretransplant visual acuity and higher rates of corneal vascularization and ocular surface disease than adults. However, 2-year post-transplant corrected visual acuity reached 20/20 or better in 35% of children compared to 28% of adults (P = .1). Transplant rejection and failure rates were 11% (P = .79) and 3% (P = .31), respectively, for children, which were comparable to rates for adults. Endothelial rejection was reported following penetrating keratoplasty (PK) in 13% of children (10% in adults). Irreversible rejection was not recorded for any transplant in a child. Despite a lack of difference in transplant outcomes, there was a significant age effect in the Cox regression model for transplant rejection, such that for every 5-year increase in age there was a 6% reduction in the hazard of rejection. Transplant survival following anterior lamellar keratoplasty and PK in children was similar. CONCLUSIONS: Young keratoconus patients have excellent transplant outcomes and visual results comparable to adults. Overall, the hazard of rejection was found to decrease with advancing age. However, in this large cohort of young patients with keratoconus and poor vision, there is no evidence of outcome advantage in delaying transplant until adult years.

Differential effects of primary disease and corneal vascularisation on corneal transplant rejection and survival.

AIMS: To investigate the relative risk of pretransplant corneal vascularisation on rate of rejection and graft failure within 5 years of surgery when categorised by indication for transplantation.We analysed all adults recorded in the UK transplant registry who had a first cornea transplant for keratoconus (KC), pseudophakic bullous keratopathy (PBK) or previous infection (viral/bacterial/fungal/protozoan) between 1999 and 2017. We analysed the number of quadrants of the recipient cornea vascularised before transplant and type of vascularisation, the interval post-transplant to rejection, if any, and the outcome at 5 years post-transplant. Risk factors for rejection and transplant failure were modelled by multivariable risk-adjusted Cox regression. RESULTS: Corneal vascularisation was recorded in 10%, 25% and 67% of patients with KC, PBK and infection, respectively. Individuals with PBK had an increased hazard of transplant rejection only when there were more than two quadrants of vascularisation (HR 1.5, p=0.004) when either superficial and/or deep vascularisation was present (HR 1.3 and 1.4, respectively, p=0.004). Individuals who had a transplant for previous infection had an increased hazard of rejection with four quadrants of vascularisation (HR 1.6, p=0.003). There was no risk-adjusted increase in transplant failure associated with vascularisation in any group. There was weak evidence of reduction in risk of rejection and/or failure associated with lamellar compared with penetrating transplantation in KC and PBK in vascularised recipient corneas. CONCLUSION: Vascularisation is a risk factor for corneal allograft rejection within 5 years. The indication for transplantation has a clinically significant effect on the magnitude of this risk.

Differential Survival of Penetrating and Lamellar Transplants in Management of Failed Corneal Grafts.

Importance: An increasing proportion of corneal transplant procedures are undertaken for replacement of a failed previous graft. The proportion of lamellar transplant procedures has significantly increased. There are limited large-scale reports on regraft procedures that may help guide surgeons and patients in their choice of surgery. Objective: To examine the corneal transplant replacement survival rates for the 3 main indications and types of regraft surgery. Design, Setting, and Participants: This national transplant registry study examined surgery and follow-up data on all corneal transplants performed in the United Kingdom from April 1, 1999, through March 31, 2016. Main Outcomes and Measures: Actuarial regraft 5-year survival rates were compared for the 3 main indications and types of graft: penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty for keratoconus, PK and endothelial keratoplasty (EK) for Fuchs endothelial dystrophy (FED), and pseudophakic bullous keratopathy (PBK). Results: A total of 9925 regrafts were analyzed during the 17-year study period. Penetrating keratoplasty represented 7261 cases (73.2%) in the cohort. Endothelial keratoplasty increased by 1361.5%, from 12 (2.6%; 95% CI, 1.3%-4.5%) of all 467 regrafts during 2005-2006 to 292 (38.0%; 95% CI, 34.6%-41.6%) of 768 during 2015-2016. The median time to first regraft for all graft types was 28 months (interquartile range, 10-64 months). When examining all graft types performed for all indications, stratification of 5-year survival was found for successive grafts, with a difference in survival of 25 270 (72.5%; 95% CI, 71.7%-73.2%) from the first graft to 4224 (53.4%; 95% CI, 51.4%-55.4%) from the second graft and 1088 (37.3%; 95% CI, 33.4%-41.3%) from the second to third graft. For first regrafts in keratoconus and PBK, survival after lamellar and PK procedures was similar. For FED, there was a higher regraft survival after PK (375 [70.8%]; 95% CI, 64.6%-76.1%) compared with EK (303 [54.7%]; 95% CI, 45.8%-62.8%) (P < .001). For FED and PBK, there was no difference in first regraft survival identified between EK followed by PK vs PK followed by PK or EK followed by EK vs PK followed by EK. Conclusions and Relevance: In this large registry-based analysis of corneal regraft survival, regraft survival was found to vary with indication for first graft surgery and for FED with type of regraft procedure performed. For FED and PBK, the permutation of graft and subsequent first regraft procedure were not associated with any survival benefit for the first regraft. These reported outcomes may assist decision-making in management of a failed corneal transplant.

The Rule of Threes: three factors that triple the likelihood of families overriding first person consent for organ donation in the UK.

Between 1 April 2012 and 31 March 2015, 263 of the 2244 families in the UK whose loved ones had registered to donate organs for transplantation after their death on the NHS Organ Donor Register chose to override this decision; an override rate of 11.7%. Multivariable logistic regression analysis was applied to data relating to various aspects of the family approach in order to identify factors associated with such overrides. The factors associated with family overrides were failure to involve the Specialist Nurse for Organ Donation in the family approach (odds ratio 3.0), donation after circulatory death (odds ratio 2.7) and Black, Asian or Minority Ethnicity (odds ratio 2.7). This highlights the need to further engage with these groups in exploring donation as an end of life choice, and suggests that there may be, from the perspective of the family, fundamental differences between donation after brainstem death and circulatory death. It further adds to the body of data linking involvement of the Specialist Nurse for Organ Donation in the family approach to improved UK consent rates.

Stability of visual outcome between 2 and 5 years following corneal transplantation in the UK.

BACKGROUND AND AIMS: Many studies of corneal transplantation focus on graft failure or rejection as endpoints, or report visual outcomes at one postoperative time point. We aimed to study the stability of visual outcomes between 2 and 5 years following corneal transplantation. METHODS: All patients with keratoconus (868) or Fuchs endothelial dystrophy (FED) (569) receiving their first corneal transplant for visual purposes in the UK between January 2003 and December 2009 were included. The probability of visual improvement or deterioration (gain or loss of ≥2 Snellen lines, respectively) between 2 and 5 years after keratoplasty was modelled by multivariable logistic regression. RESULTS: The majority of keratoconus patients with a penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty maintained their visual acuity (651/868; 75%) while 15% (133/868) improved and 10% (84/868) deteriorated. Similarly, most patients with FED who received a PK maintained their vision (395/569; 70%) while 18% (105/569) improved and 12% (68/569) deteriorated.