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Platelet transfusion refractoriness results in adverse outcomes and increased health care costs. Managing refractoriness resulting from HLA alloimmunization necessitates the use of HLA antigen–matched platelets but requires a large platelet donor pool and does not guarantee full matching. We report the first randomized, double-blind, noninferiority, crossover trial comparing HLA epitope–matched (HEM) platelets with HLA standard antigen–matched (HSM) platelet transfusions. Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia were eligible. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to 8 prophylactic HEM and HSM transfusions provided in random order. The primary outcome was 1-hour posttransfusion platelet count increment (PCI). Forty-nine patients were randomized at 14 UK hospitals. For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean PCIs for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively (adjusted mean difference, −0.1; 95% confidence interval [CI], −2.9 to 2.8). Because the lower limit of the 95% CI was not greater than the predefined noninferiority limit, the HEM approach was declared noninferior to the HSM approach. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments. For every additional epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope-matched platelets should be considered to support HLA alloimmunized patients. This trial was registered at www.isrctn.com as #ISRCTN23996532.

BACKGROUND: Platelet transfusions are commonly used to prevent bleeding in preterm infants with thrombocytopenia. Data are lacking to provide guidance regarding thresholds for prophylactic platelet transfusions in preterm neonates with severe thrombocytopenia. METHODS: In this multicenter trial, we randomly assigned infants born at less than 34 weeks of gestation in whom severe thrombocytopenia developed to receive a platelet transfusion at platelet-count thresholds of 50,000 per cubic millimeter (high-threshold group) or 25,000 per cubic millimeter (low-threshold group). Bleeding was documented prospectively with the use of a validated bleeding-assessment tool. The primary outcome was death or new major bleeding within 28 days after randomization. RESULTS: A total of 660 infants (median birth weight, 740 g; and median gestational age, 26.6 weeks) underwent randomization. In the high-threshold group, 90% of the infants (296 of 328 infants) received at least one platelet transfusion, as compared with 53% (177 of 331 infants) in the low-threshold group. A new major bleeding episode or death occurred in 26% of the infants (85 of 324) in the high-threshold group and in 19% (61 of 329) in the low-threshold group (odds ratio, 1.57; 95% confidence interval [CI], 1.06 to 2.32; P=0.02). There was no significant difference between the groups with respect to rates of serious adverse events (25% in the high-threshold group and 22% in the low-threshold group; odds ratio, 1.14; 95% CI, 0.78 to 1.67). CONCLUSIONS: Among preterm infants with severe thrombocytopenia, those randomly assigned to receive platelet transfusions at a platelet-count threshold of 50,000 per cubic millimeter had a significantly higher rate of death or major bleeding within 28 days after randomization than those who received platelet transfusions at a platelet-count threshold of 25,000 per cubic millimeter. (Funded by the National Health Service Blood and Transplant Research and Development Committee and others; Current Controlled Trials number, ISRCTN87736839 .).

SUMMARYObjective To describe the epidemiology of blood transfusion in children: including the incidence of transfusion, the diagnoses leading to transfusion, donor exposure (DE) and post-transfusion survival. Study design and methods The Epidemiology and Survival of Transfusion Recipients (EASTR) Study was a multi-centre epidemiological study with prospective survival monitoring. Cross-sectional sampling of adult and paediatric transfusion recipients in 29 hospitals was used to select three separate cohorts of red cell (RBC), platelet (PLT) and fresh frozen plasma (FFP) recipients between October 2001 and September 2002. This paper presents the analysis of results for children

Look-back studies of blood transfusion in Creutzfeldt-Jakob disease commonly rely on reported history from surrogate witnesses. Data from the UK Transfusion Medicine Epidemiology Review have been analysed to determine the accuracy of the blood donation history provided by the relatives of cases. Our results show that only a small percentage of cases were found to be registered as donors on UK Blood Service (UKBS) databases when there was no family report of blood donation. In contrast, a history of reported donation was less accurate.

Background Low fibrinogen (Fg) concentrations in trauma haemorrhage are associated with poorer outcomes. Cryoprecipitate is the standard source for Fg administration in the UK and USA and is often given in the later stages of transfusion therapy. It is not known whether early cryoprecipitate therapy improves clinical outcomes. The primary aim of this feasibility study was to determine whether it was possible to administer cryoprecipitate, within 90 min of admission to hospital. Secondary aims were to evaluate laboratory measures of Fg and clinical outcomes including thrombotic events, organ failure, length of hospital stay and mortality. Methods This was an unblinded RCT, conducted at two civilian UK major trauma centres of adult trauma patients (age ≥16 yrs), with active bleeding and requiring activation of the major haemorrhage protocol. Participants were randomised to standard major haemorrhage therapy (STANDARD) (n=22), or to standard haemorrhage therapy plus two early pools of cryoprecipitate (CRYO) (n=21). Results 85% (95% CI: 69–100%) CRYO participants received cryoprecipitate within 90 min, median time 60 min (IQR: 57–76) compared with 108 min (67–147), CRYO and STANDARD arms respectively (P=0.002). Fg concentrations were higher in the CRYO arm and were maintained above 1.8 g litre−1 at all time-points during active haemorrhage. All-cause mortality at 28 days was not significantly different (P=0.14). Conclusions Early Fg supplementation using cryoprecipitate is feasible in trauma patients. This study supports the need for a definitive RCT to determine the effect of early Fg supplementation on mortality and other clinical outcomes. Trial registry number ISRCTN55509212.

BACKGROUND: Bacterial screening offers the possibility of extending platelet (PLT) storage to Day 7. We conducted a noninferiority, crossover trial comparing PLTs stored for 6 or 7 days versus 2 to 5 days. STUDY DESIGN AND METHODS: Stable hematology patients were allocated to receive blocks of 2- to 5- and 6- or 7-day PLTs in random order. The primary outcome was the proportion of successful transfusions during the first block, defined as a corrected count increment (CCI) of more than 4.5 at 8 to 24 hours posttransfusion. RESULTS: Of 122 patients with an evaluable first block, 87 (71%) and 84 (69%) had successful transfusions after 2- to 5- and 6- or 7-day PLTs of mean (SD) ages of 3.8 (1.0) and 6.4 (0.5) days, respectively. Six- or 7-day PLTs were declared noninferior to 2- to 5-day PLTs since the upper confidence interval (CI) limit was less than the predefined noninferiority margin of 10% (95% CI, -14.0% to 9.1%; p = 0.766). Logistic regression analysis gave an adjusted odds ratio of 0.86 (95% CI, 0.47-1.58; p = 0.625). Mean (SD) 8- to 24-hour CCIs were 9.4 (7.9) and 7.7 (7.1) after transfusion with 2- to 5- or 6- or 7-day PLTs (95% CI, -3.31 to 0.03; p = 0.054). The proportions of days with bleeding scores of WHO Grade 2 or higher were 13% (38/297 days) and 11% (32/296 days; 95% CI, -3.2 to 7.2; p = 0.454). Median interval to next PLT transfusion (2 days) was unaffected (95% CI, -10.5 to 5.4; p = 0.531). CONCLUSION: In hematology patients, there was no evidence that 6- or 7-day PLTs were inferior to 2- to 5-day PLTs, as measured by proportion of patients with successful transfusions, bleeding events, or interval to next transfusion.

The effect of variation in platelet function in platelet donors on patient outcome following platelet transfusion is unknown. This trial assessed the hypothesis that platelets collected from donors with highly responsive platelets to agonists in vitro assessed by flow cytometry (high-responder donors) are cleared more quickly from the circulation than those from low-responder donors, resulting in lower platelet count increments following transfusion. This parallel group, semirandomized double-blinded trial was conducted in a single center in the United Kingdom. Eligible patients were those 16 or older with thrombocytopenia secondary to bone marrow failure, requiring prophylactic platelet transfusion. Patients were randomly assigned to receive a platelet donation from a high- or low-responder donor when both were available, or when only 1 type of platelet was available, patients received that. Participants, investigators, and those assessing outcomes were masked to group assignment. The primary end point was the platelet count increment 10 to 90 minutes following transfusion. Analysis was by intention to treat. Fifty-one patients were assigned to receive platelets from low-responder donors, and 49 from high-responder donors (47 of which were randomized and 53 nonrandomized). There was no significant difference in platelet count increment 10 to 90 minutes following transfusion in patients receiving platelets from high-responder (mean, 21.0 × 109/L; 95% confidence interval [CI], 4.9-37.2) or low-responder (mean, 23.3 × 109/L; 95% CI, 7.8-38.9) donors (mean difference, 2.3; 95% CI, -1.1 to 5.7; P = .18). These results support the current policy of not selecting platelet donors on the basis of platelet function for prophylactic platelet transfusion.

Background and Objectives In this study, we compare variant Creutzfeldt-Jakob disease (vCJD) cases definitely linked to blood transfusion, those with a history of blood transfusion in which no donor has developed vCJD and primary cases with no history of blood transfusion. The aim is to determine whether there are any differences in the demographics or clinical phenotype in these groups that might suggest additional cases of transfusion transmission of vCJD. Materials and Methods All cases of vCJD who are old enough to donate blood (i.e. >17 years old) are notified to the UKBTS at diagnosis, regardless of whether they are known to have a blood donation history. A search is then made for donor records and, if found, all components produced and issued to hospitals are identified and their fate determined. Recipient details are then checked against the NCJDRSU register to establish whether there is a match between these individuals and patients who have been diagnosed with vCJD. In the reverse study, attempts are made to trace the donors to all cases reported to have received a blood transfusion and donors' details are checked against the register to determine if any have developed vCJD. Results Of the 177 cases of vCJD diagnosed in the UK as of 1 February 2014, the TMER study identified 15 cases reported to have received a blood transfusion. Transfusion records were unavailable for 4 of these cases, all pre-1980, and in one other case there was no transfusion recorded in the medical notes. Transfusion records were found for 10 cases. One case transfused at symptom onset was excluded from this analysis. The mean age at onset of symptoms of the remaining nine transfusion recipients (four female and five male) was 42·9 years; 57·6 years in the three known transfusion-transmitted cases and 35·5 years in the six not linked cases. In one of these cases, details of components transfused were unavailable, and the remaining five cases received a total of 116 donor exposures with 112 donors identified, none of whom is known to have developed clinical vCJD. To date, five of the 112 identified donors have died and none was certified as dying of vCJD or any other neurological disorder. Two of the transfusion-transmitted cases did not fulfil diagnostic criteria for probable vCJD during life but were confirmed at post-mortem. Both cases were in the older age range (68 and 74 years, respectively), and neither had a positive MRI brain scan. The remaining cases all fulfilled the criteria for the diagnosis of vCJD in life, but two of these had atypical features and were older than the expected age at onset for vCJD. Conclusion In conclusion, it is possible that one or more of the vCJD cases that received a blood transfusion derived from an individual not known to have vCJD were infected by the blood transfusion. However, the evidence for this is weak, and the absence of a past history of transfusion in most cases of vCJD excludes a large number of unrecognised transfusion-transmitted cases.

Background This cost analysis uses data from a randomized trial comparing a no prophylaxis versus prophylactic platelet (PLT) transfusion policy (counts

Background A recent randomized trial compared a policy of no prophylaxis with a policy of prophylactic platelet (PLT) transfusions at counts of fewer than 10 × 109/L in patients with hematologic malignancies. The results suggested the effectiveness of prophylactic PLT transfusions may vary according to patient diagnosis and treatment plan. Study Design and Methods This article presents full subgroup analyses and compares treatment effects between autologous hematopoietic stem cell transplantation (autoHSCT; n = 421) and chemotherapy/allogeneic HSCT (chemo/alloHSCT; n = 179) patients. Results Prespecified subgroup analysis found that the reduction in proportion of patients experiencing WHO Grade 2 to 4 bleeds (main trial outcome) seen in the prophylaxis arm was of greater magnitude in chemo/alloHSCT than autoHSCT patients (interaction p = 0.04). Analysis of secondary outcomes showed a shorter time to first bleeding episode with no prophylaxis in the chemo/alloHSCT group (hazard ratio, 1.84; 95% confidence interval CI, 1.21-2.79; p = 0.004) compared to the autoHSCT group (hazard ratio, 1.12; 95% CI, 0.85-1.48; p = 0.4; interaction p = 0.08). The increased number of days with Grade 2 to 4 bleeds with a no-prophylaxis policy was similar in chemo/alloHSCT (rate ratio, 1.89; 95% CI, 1.10-3.26) and in autoHSCT patients (rate ratio, 1.43; 95% CI, 1.04-1.97). Both subgroups showed significant reductions in PLT transfusions with a no-prophylaxis strategy. Conclusion There is evidence that the effectiveness of prophylactic PLT transfusions may differ between subgroups, with chemo/alloHSCT patients receiving prophylactic PLT transfusions appearing to show a greater reduction in bleeding outcomes compared to patients following a no-prophylaxis policy.

The study’s objective was to assess the cost-effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle cell disease (HbSS/Ss 0 thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis based on evidence from that trial is presented. A decision-analytic model is used to incorporate long-term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality-adjusted life years (QALYs), are reported from the ‘within-trial’ analysis and for the decision-analytic model. The probability of cost-effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from � £813 to £26. All scenarios suggested preoperative transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness threshold of £20 000 per QALY.

BACKGROUND: The effectiveness of platelet transfusions to prevent bleeding in patients with hematologic cancers remains unclear. This trial assessed whether a policy of not giving prophylactic platelet transfusions was as effective and safe as a policy of providing prophylaxis. METHODS: We conducted this randomized, open-label, noninferiority trial at 14 centers in the United Kingdom and Australia. Patients were randomly assigned to receive, or not to receive, prophylactic platelet transfusions when morning platelet counts were less than 10×10(9) per liter. Eligible patients were persons 16 years of age or older who were receiving chemotherapy or undergoing stem-cell transplantation and who had or were expected to have thrombocytopenia. The primary end point was bleeding of World Health Organization (WHO) grade 2, 3, or 4 up to 30 days after randomization. RESULTS: A total of 600 patients (301 in the no-prophylaxis group and 299 in the prophylaxis group) underwent randomization between 2006 and 2011. Bleeding of WHO grade 2, 3, or 4 occurred in 151 of 300 patients (50%) in the no-prophylaxis group, as compared with 128 of 298 (43%) in the prophylaxis group (adjusted difference in proportions, 8.4 percentage points; 90% confidence interval, 1.7 to 15.2; P=0.06 for noninferiority). Patients in the no-prophylaxis group had more days with bleeding and a shorter time to the first bleeding episode than did patients in the prophylaxis group. Platelet use was markedly reduced in the no-prophylaxis group. A prespecified subgroup analysis identified similar rates of bleeding in the two study groups among patients undergoing autologous stem-cell transplantation. CONCLUSIONS: The results of our study support the need for the continued use of prophylaxis with platelet transfusion and show the benefit of such prophylaxis for reducing bleeding, as compared with no prophylaxis. A significant number of patients had bleeding despite prophylaxis. (Funded by the National Health Service Blood and Transplant Research and Development Committee and the Australian Red Cross Blood Service; TOPPS Controlled-Trials.com number, ISRCTN08758735.).

Summary Background No consensus exists on whether preoperative blood transfusions are beneficial in patients with sickle-cell disease. We assessed whether perioperative complication rates would be altered by preoperative transfusion. Methods We did a multicentre, randomised trial. Eligible patients were aged at least 1 year, had haemoglobin SS or Sβ 0 thalassaemia sickle-cell-disease subtypes, and were scheduled for low-risk or medium-risk operations. Patients were randomly assigned no transfusion or transfusion no more than 10 days before surgery. The primary outcome was the proportion of clinically important complications between randomisation and 30 days after surgery. Analysis was by intention to treat. Findings 67 (96%) of 70 enrolled patients—33 no preoperative transfusion and 34 preoperative transfusion—were assessed. 65 (97%) of 67 patients had the haemoglobin SS subtype and 54 (81%) were scheduled to undergo medium-risk surgery. 13 (39%) of 33 patients in the no-preoperative-transfusion group had clinically important complications, compared with five (15%) in the preoperative-transfusion group (p=0·023). Of these, 10 (30%) and one (3%), respectively, had serious adverse events. The unadjusted odds ratio of clinically important complications was 3·8 (95% CI 1·2–12·2, p=0·027). 10 (91%) of 11 serious adverse events were acute chest syndrome (nine in the no-preoperative-transfusion group and one in the preoperative-transfusion group). Duration of hospital stay and readmission rates did not differ between study groups. Interpretation Preoperative transfusion was associated with decreased perioperative complications in patients with sickle-cell disease in this trial. This approach could, therefore, be beneficial for patients with the haemoglobin SS subtype who are scheduled to undergo low-risk and medium-risk surgeries. Funding NHS Blood and Transplant.

Acute upper gastrointestinal bleeding (AUGIB) is the commonest reason for hospitalization with hemorrhage in the UK and the leading indication for transfusion of red blood cells (RBCs). Observational studies suggest an association between more liberal RBC transfusion and adverse patient outcomes, and a recent randomised trial reported increased further bleeding and mortality with a liberal transfusion policy. TRIGGER (Transfusion in Gastrointestinal Bleeding) is a pragmatic, cluster randomized trial which aims to evaluate the feasibility and safety of implementing a restrictive versus liberal RBC transfusion policy in adult patients admitted with AUGIB. The trial will take place in 6 UK hospitals, and each centre will be randomly allocated to a transfusion policy. Clinicians throughout each hospital will manage all eligible patients according to the transfusion policy for the 6-month trial recruitment period. In the restrictive centers, patients become eligible for RBC transfusion when their hemoglobin is < 8 g/dL. In the liberal centers patients become eligible for transfusion once their hemoglobin is < 10 g/dL. All clinicians will have the discretion to transfuse outside of the policy but will be asked to document the reasons for doing so. Feasibility outcome measures include protocol adherence, recruitment rate, and evidence of selection bias. Clinical outcome measures include further bleeding, mortality, thromboembolic events, and infections. Quality of life will be measured using the EuroQol EQ-5D at day 28, and the costs associated with hospitalization for AUGIB in the UK will be estimated. Consent will be sought from participants or their representatives according to patient capacity for use of routine hospital data and day 28 follow up. The study has ethical approval for conduct in England and Scotland. Results will be analysed according to a pre-defined statistical analysis plan and disseminated in peer reviewed publications to relevant stakeholders. The results of this study will inform the feasibility and design of a phase III randomized trial. © 2013 Elsevier Inc.

Objective/Aim: To evaluate the safety of transfusing pooled, whole blood-derived granulocytes in additive solution and plasma (GASP) in 30 recipients. Background: Demand for granulocytes in England has increased five-fold. With the advantages of reduced red cell, plasma and overall volume, GASP maintains function in vitro. Methods and Materials: Observations were recorded prior to and post transfusion. Increments were recorded at 1 h and the following morning. Leucocyte antibody screening was undertaken prior to and at 1–6 months following transfusion. Results: Thirty patients aged between 8 months and 68 years received 221 GASP in 148 transfusion episodes. GASP contained an average of 1·0 ×1010 granulocytes in 207 mL. Adults usually received two packs and children 10–20 mL kg–1. Children and adults received a median [interquartile range (IQR)] dose of 12·5 (9·1–25·3) and 19·7 (12·0–25·8) ×109 granulocytes per transfusion, respectively. There was one episode of transfusion-associated circulatory overload (TACO) in a patient with chronic cardiac failure following 600 mL of unpooled granulocytes, other fluids and one GASP. New leucocyte alloimmunisation occurred in 3/30 recipients 10%. No other significant reactions were reported. Median peripheral blood neutrophil increments at 1 h post transfusion were 0·06 (IQR, 0·01–0·17) in children and (0·03) (IQR, 0–0·16) in adults. Conclusion: GASP has a similar safety profile to other sources of granulocytes for patients with refractory infection or in need of secondary prophylactic transfusion. Further studies are required to clarify the role of GASP in the treatment of neutropenic patients.

Although considerable advances have been made in many aspects of platelet transfusion therapy in the last 30 years, some areas continue to provoke debate, including the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding in patients with bone marrow failure. We have designed a randomized controlled trial to compare prophylactic platelet use with a threshold of a platelet count of 10 × 10 9 /L with no prophylaxis in adult thrombocytopenic patients with hematologic malignancies. The trial question is whether a no-prophylactic policy for the use of platelet transfusions in patients with hematologic malignancies is not inferior to a threshold prophylactic policy at 10 × 10 9 /L, for bleeding at World Health Organization (WHO) grade 2, 3, or 4, up to 30 days from randomization. The primary outcome measure is the proportion of patients who have a significant clinical bleed, defined as WHO grade 2 or higher up to 30 days from randomization. Subsidiary clinical outcome measures include time to first bleed and a descriptive analysis of all severe bleeds. A bleeding assessment form is completed daily for all study subjects until day 30 from randomization. Minor modifications were made to the definitions at WHO grades 1 and 2 for petechiae and duration of nose bleeds, after piloting of the bleeding assessment forms. This study has been designed as a 2-stage randomized trial with an interim analysis planned after a minimum of 100 patients had been randomized and had completed their period of observation. Patients have initially been enrolled through 3 United Kingdom hematology centers. The interim analysis has been completed, and the results have confirmed a final sample size of 600 patients. Recruitment is now being extended to other centers in United Kingdom and Australia. Local research nurses are not blinded to treatment allocation, but a number of measures to reduce risk of assessment bias include repeated education around standard operating procedures, common definitions, and duplication of assessments. The expected completion date for the 5-year study is December 2011.

BACKGROUND: To date there have been four instances of infection transmitted through blood transfusions derived from individuals who later developed variant Creutzfeldt-Jakob disease (vCJD). The identification of further transmission of vCJD through this route would have important implications for risk assessment and public health. STUDY DESIGN AND METHODS: Through the UK Transfusion Medicine Epidemiology Review (TMER) the fate of blood donations from individuals who develop vCJD is traced and recipients of labile components are identified. The details of recipients are cross-checked with the register of vCJD cases held at the National CJD Surveillance Unit (NCJDSU) to identify any linkage between donors and recipients. In the reverse study, when individuals with vCJD are found to have a history of blood transfusion the donors of the transfused blood components are traced and their details cross-checked with the vCJD register to identify any missed or unrecognized linkage between donors and recipients. CASE REPORT: A case of vCJD has been identified with a history of blood transfusion in infancy. The donors who provided the components transfused cannot be identified, but a blood donor known to have donated blood to another individual who subsequently developed vCJD could have been a donor to the index case. RESULTS: The at-risk donor is alive 20 years after the relevant donation and continued to donate for some years, until identified as at risk, with 27 other blood components issued for use in patients, none of whom are known to have developed vCJD. CONCLUSION: Circumstantial evidence has raised the possibility that the case in this report represents a further instance of transfusion transmission of vCJD. However, detailed investigation indicates that the pattern of events may have occurred by chance and disease in this individual may have been caused by transmission of bovine spongiform encephalopathy infection, as is the presumed cause in other primary cases of vCJD.

Background The risk to public health of onward transmission of variant Creutzfeldt–Jakob disease (vCJD) via blood transfusion and plasma product administration is of on-going concern, particularly with the recent reported detection of abnormal prion protein in a person with haemophilia. Objectives To describe the history of fractionated plasma product exposure in clinical cases of vCJD in the UK. Methods Through examination of records held at the National CJD Surveillance Unit (from relatives, general practices and hospitals). Results Nine out of 168 UK vCJD cases had a history of receipt of fractionated plasma products on 12 different occasions (1 pre-vCJD risk in 1970, the remaining between 1989–1998). According to the UK CJD Incident Panel risk assessment criteria, 11 were low-risk products and one was low or medium risk. Conclusion It is unlikely that any of the UK vCJD clinical cases to date were infected through exposure to fractionated plasma products. However, the possibility that such transmission may result in vCJD cases in the future cannot be excluded.

To gather data on current preoperative transfusion practice and postoperative complications in sickle cell disease (SCD) as a prelude to a randomised trial.A prospective one year survey of 114 SCD patients undergoing elective surgery in 31 English hospitals was undertaken.43%, 39% and 23% of patients respectively [corrected] received no transfusion, top-up and exchange transfusion preoperatively. Overall postoperative complication rates were 18%, 26% and 17%, with SCD related complications of 12%, 8% and 0% respectively. 85% of patients with [corrected]HbSC/HbSss(+)thalassaemia and 71% of obstetric and gynaecology patients were not transfused preoperatively, whereas 59% patients undergoing ENT procedures and 83% of hip replacements had top-up and exchange transfusions respectively. Multivariable logistic regression analysis revealed that having moderate/high risk procedures was a predictor of postoperative complications (OR 4.9 (95% CL: 1.3 to 18), P = 0.017) [corrected] while preoperative transfusion was not (OR 1.7, (95% CL: [corrected] 0.5 to 6), P = 0.41).The lack of clear benefit of transfusion confirms the need for a randomised controlled trial of transfusion vs. no transfusion in patients with HbSS and HbSss(0)thalassaemia.

The use of patient-identifiable data in epidemiological research is subject to increasingly complex regulation. This article reports the experience of a research team in setting up the Epidemiology and Survival of Transfusion Recipients (EASTR) study in which patient-identifiable information was needed in order to link data from two sources for analysis and obtain long-term survival patterns of transfusion recipients. The process of establishing the study involved obtaining separate ethical, research and development and data protection approval, including application to the newly formed Patient Information Advisory Group, set up under Section 60 of the Health and Social Care Act, 2001. We describe the high cost in administrative procedures and time now necessary to gain statutory approval before such a study can begin, which has been the result of recent legislation. Issues arising from our experience are discussed.

BACKGROUND: A before and after study was under- taken to investigate the effect of universal leukoreduction (ULR) in the UK on postoperative length of hospital stay (LOS) and infections. STUDY DESIGN AND METHODS: Consecutive patients undergoing elective coronary artery bypass grafting or total hip and/or knee replacement in 11 hospitals received non-WBC-reduced RBCs before implementation of ULR (T1, n = 997) or WBC-reduced RBCs after implementation of ULR (T2, n = 1098). RESULTS: Patients in T1 and T2 were comparable except patients in T2 received on average more units of RBCs but had lower discharge Hct levels. Postoperative LOS (T1, 10 ± 8.9 days; T2, 9.6 ± 6.9 days) and the proportion of patients with suspected and proven post- operative infections (T1, 21.0%; T2, 20.0%) were unchanged before and after ULR (LOS, hazard ratio 1.01, 95% CI 0.92-1.10; infections, OR 0.83, 95% CI 0.77-1.02). Subgroup analysis showed no significant interaction between storage age or dose of blood on responsiveness of primary outcomes to ULR. Secondary outcomes were unchanged overall. Analysis by surgical procedure gave conflicting results with both increased mortality (p = 0.031) and an increased proportion of cardiac patients with proven infections (p = 0.004), whereas the proportion of orthopedic patients with proven infections was reduced (p = 0.002) after ULR. CONCLUSION: Implementation of ULR had no major impact on postoperative infection or LOS in patients undergoing elective surgical procedures who received transfusion(s). Smaller effects, either detrimental or beneficial of ULR, cannot be excluded.

BACKGROUND: Virus inactivation of pooled fresh-frozen plasma (FFP) by the solvent/detergent (SD) method results in a loss of approximately 20 percent of factor VIII. This study aimed to assess the efficacy of SD-treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation. STUDY DESIGN AND METHODS: Forty-nine patients with coagulation deficits due to liver disease, who required FFP for invasive procedures or liver transplantation, were randomly assigned to receive either FFP or SD-treated plasma. Patients were assessed for side effects, correction of coagulopathy over 24 hours, and seroconversion for viral markers 6 to 18 months after treatment. RESULTS: In the liver disease group, equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD-treated plasma, with a similar return to baseline values over 24 hours. There was greater correction of the International Normalised Ratio in patients receiving SD-treated plasma (p = 0.037), but this patient group had higher baseline values than recipients of FFP (p = 0.024). Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD-treated plasma. The use of other blood components during transplantation was identical in the two treatment groups. No seroconversions were seen for HIV or hepatitis B or C virus. One patient who had received FFP seroconverted for human parvovirus B19. Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies, as later testing of these patients gave negative results. Minor side effects were rare in both groups. CONCLUSION: SD-treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation. Assessment of seroconversion for viral markers in recipients of plasma-derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected.

This study, conducted for the UK Blood Transfusion Services (UKBTS), evaluated the clinical safety of red cells filtered through a CE-marked prion removal filter (P-Capt™). Patients requiring blood transfusion for elective procedures in nine UK hospitals were entered into a non-randomized open trial to assess development of red cell antibodies to standard red cell (RCC) or prion-filtered red cell concentrates (PF-RCC) at eight weeks and six months post-transfusion. Patients who received at least 1 unit of PF-RCC were compared with a control cohort given RCC only. About 917 PF-RCC and 1336 RCC units were transfused into 299 and 291 patients respectively. Twenty-six new red cell antibodies were detected post-transfusion in 10 patients in each arm, an overall alloimmunization rate of 4.4%. Neither the treatment arm [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.3, 2.5] nor number of units transfused (OR 0.95, 95% CI 0.8, 1.1) had a significant effect on the proportion of patients who developed new alloantibodies. No pan-reactive antibodies or antibodies specifically against PF-RCC were detected. There was no difference in transfusion reactions between arms, and no novel transfusion-related adverse events clearly attributable to PF-RCC were seen. These data suggest that prion filtration of red cells does not reduce overall transfusion safety. This finding requires confirmation in large populations of transfused patients.

Background To date, four instances of probable transfusion–transmission of variant Creutzfeldt–Jakob disease (vCJD) infection have been described, and surviving recipients of vCJD-implicated blood components have been informed that they may be ‘at risk’ of vCJD. Nearly two-thirds of all recipients of vCJD-implicated blood components are deceased, and many died before the vCJD risk was known. The primary aim of this study was to determine retrospectively whether there was evidence that any of the other deceased recipients of vCJD-implicated blood components had any clinical signs or symptoms suggestive of vCJD in life. In addition, pathological material from recipients, stored at the time of surgery or autopsy, was sought to allow testing for evidence of vCJD infection. A secondary aim of the study was to obtain information on invasive healthcare procedures undertaken on recipients following the transfusion to identify the potential for onward transmission of infection. Methods A retrospective review of medical case notes of deceased recipients of vCJD-implicated blood components was carried out, and relevant information was extracted. In cases undergoing post-mortem, details of the findings were obtained. Results The medical case notes of 33 (83%) deceased recipients of vCJD-implicated blood components, not already known to be infected with vCJD, were reviewed. The median age of recipients was 68 years (interquartile range 57–79 years). Almost half (16) were male. The median time from transfusion to death was 175 days (interquartile range 43–701 days). Most (66%) recipients died in hospital. None of the recipients had documented evidence of clinical signs or symptoms suggestive of vCJD. Only two recipients, both of whom died within a year of transfusion, underwent autopsy examination. Neither brain nor peripheral lymphoreticular tissue was available from either recipient, and pathological material was unavailable from any of the other deceased recipients. Almost half of all recipients underwent at least one invasive healthcare procedure post-transfusion. Conclusions A retrospective review of the medical case notes of the deceased recipients of vCJD-implicated blood components found no evidence that any further cases expressed clinical signs or symptoms suggestive of vCJD during life, but only four of the recipients survived for more than 5 years post-transfusion.

Background and Objectives This paper reports the results to 1 March 2006 of an ongoing UK study, the Transfusion Medicine Epidemiological Review (TMER), by the National CJD Surveillance Unit (NCJDSU) and the UK Blood Services (UKBS) to determine whether there is any evidence that Creutzfeldt–Jakob disease (CJD), including sporadic CJD (sCJD), familial CJD (fCJD), and variant CJD (vCJD) is transmissible via blood transfusion. Materials and Methods Sporadic CJD and fCJD cases with a history of blood donation or transfusion are notified to UKBS. All vCJD cases aged > 17 years are notified to UKBS on diagnosis. A search for donation records is instigated and the fate of all donations is identified by lookback. For cases with a history of blood transfusion, hospital and UKBS records are searched to identify blood donors. Details of identified recipients and donors are checked against the NCJDSU register to establish if there are any matches. Results CJD cases with donation history: 18/31 vCJD, 3/93 sCJD, and 3/5 fCJD cases reported as blood donors were confirmed to have donated labile components transfused to 66, 20, and 11 recipients respectively. Two vCJD recipients have appeared on the NCJDSU register as confirmed and probable vCJD cases. The latter developed symptoms of vCJD 6.5 years and 7.8 years respectively after receiving non-leucodepleted red blood cells (RBCs) from two different donors who developed clinical symptoms approximately 40 and 21 months after donating. A third recipient, given RBC donated by a further vCJD case approximately 18 months before onset of clinical symptoms, had abnormal prion protein in lymphoid tissue at post-mortem (5-years post-transfusion) but had no clinical symptoms of vCJD. CJD cases with history of transfusion: Hospital records for 7/11 vCJD and 7/52 sCJD cases included a history of transfusion of labile blood components donated by 125 and 24 donors respectively. Two recipients who developed vCJD were linked to donors who had already appeared on the NCJDSU register as vCJD cases (see above). No further links were established. Conclusion This study has identified three instances of probable transfusion transmission of vCJD infection, including two confirmed clinical cases and one pre- or sub-clinical infection. This study has not provided evidence, to date, of transmission of sCJD or fCJD by blood transfusion, but data on these forms of diseases are limited.

Summary Background Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease caused by infection with the agent of bovine spongiform encephalopathy (BSE). Epidemiological evidence does not suggest that sporadic CJD is transmitted from person to person via blood transfusion, but this evidence may not apply to vCJD. We aimed to identify whether vCJD is transmissible through blood transfusion. Methods The national CJD surveillance unit reported all cases of probable or definite vCJD to the UK blood services, which searched for donation records at blood centres and hospitals. Information on named recipients and donors was provided to the surveillance unit to establish if any matches existed between recipients or donors and the database of cases of vCJD. Recipients were also flagged at the UK Office of National Statistics to establish date and cause of death. Findings 48 individuals were identified as having received a labile blood component from a total of 15 donors who later became vCJD cases and appeared on the surveillance unit's register. One of these recipients was identified as developing symptoms of vCJD 6·5 years after receiving a transfusion of red cells donated by an individual 3·5 years before the donor developed symptoms of vCJD. Interpretation Our findings raise the possibility that this infection was transfusion transmitted. Infection in the recipient could have been due to past dietary exposure to the BSE agent. However, the age of the patient was well beyond that of most vCJD cases, and the chance of observing a case of vCJD in a recipient in the absence of transfusion transmitted infection is about 1 in 15 000 to 1 in 30 000.

Genetic variation is known to account for up to 70% of the wide variation in platelet function observed in healthy individuals. We have shown that platelet concentrates (PC) that are highly activated when collected by apheresis are produced from donors whose platelets are highly responsive to adenosine diphosphate (ADP) and collagen related peptide (CRP-XL) in vitro(high responder donors) with activation being measured by P-selectin expression and fibrinogen binding. The effect of this variation in donors on the outcome from platelet transfusion is unknown. The aim of the PROmPT trial (Platelet Responsiveness and Outcome from Platelet Transfusion, ISRCTN 56366401) was to test the hypothesis that PC following transfusion from high responder donors are cleared more rapidly from the circulation than PC from low responder donors. Method We established a cohort of 1,000 blood donors phenotyped for responsiveness to CRP (0.1-0.5 µg/mL) or ADP (10-7M) by flow cytometry. A sub-set of these individuals (26 high and 19 low responder donors) who reproducibly had global responses, i.e. not outliers for just one agonist, in the top and bottom 10% of the cohort were selected to supply apheresis platelets collected on the Terumo Trima system for the trial. The trial was designed as a parallel group, semi-randomised double-blinded trial in stable haematology patients who required prophylactic platelet transfusions. Based on 80% power, a 5% significance level, and a presumed 10% dropout, 100 patients (with the aim of 50 receiving a unit from high responders and 50 from low responders) were required to detect a mean difference of 7x109/L in the primary endpoint of the 1 hour (10-90 min) count increment (CI) between the high and low responder PC. Patients were randomised to receive a single PC from either a high or low responder donor when both were available. If only one type of PC was available then patients received that PC. Patients with factors known to affect platelet CI were excluded. In addition, 30 patients acted as controls, receiving non-trial PC from random donors. PCs were ABO and Rh compatible. Patients were followed up for 5 days or until their next platelet transfusion. Secondary outcomes included an assessment of bleeding score (modified WHO score) both by the patient and the clinician, 24 hour (12-36 hours) CI, as well as time to next platelet transfusion, and red cell transfusion requirements. CIs were adjusted for confounding factors that affect platelet increments, these were age and dose of PC, and body surface area. Results Baseline characteristics of patients were adequately balanced between groups. Fifty one patients received a PC from low responder donors, and 49 from high responder donors (47 of which were randomised and 53 non-randomised) and 30 patients received non-trial units (2 non trial transfusions were excluded from final analysis). There was no significant difference in the adjusted 1 hour CI, in patients receiving platelets from high or low responder donors (high response 21.04 versus low response 23.34x109/L; difference 2.30, 95%CI -1.09 to 5.69, p = 0.18) or the 24 hour platelet CI (high response 12.9 versus low response 14.31x109/L; difference 1.41, 95% CI -1.96 to 4.78, p = 0.41). There were no significant differences in all other secondary outcomes between patients receiving PC from high or low responder donors, including maximum bleeding scores (odds ratio 0.78, 95%confidence interval 0.29 to 2.16, p=0.64) and bleeding rates (number of days with Grade 2-4 bleed) (rate ratio was 0.70, 95% confidence interval 0.16 to 2.97, p = 0.63). In addition, there was no significant difference in 1 hour CI between patients receiving non-trial units and those from high (p = 0.28) or low responders (p = 0.95) or in any secondary outcomes. Conclusions Results from this trial suggest that in a setting of prophylactic transfusion, the platelet responsiveness of the donor does not affect platelet count increments, bleeding scores, inter-transfusion interval or red cell usage in recipients. Further studies will be required to determine whether PC derived from high responders may be more efficacious in patients who are actively bleeding at the time of transfusion. Disclosures No relevant conflicts of interest to declare.

Background: Viral transmission remains a residual risk in single unit blood component therapy. Virus inactivation of pooled fresh frozen plasma (FFP) by the solvent/detergent (SD) method can be used to reduce this risk but results in some loss of factor activity including factor VIII and (2-anuplasmin. This study was aimed at assessing the clinical effectiveness solvent/detergent treated pooled fresh frozen plasma (SDFFP) in the correction of the coagulopathy seen during Orthotopic Liver Transplantation (OLT) as compared with standard FFP. Method: Twenty eight patients with an underlying derangement of coagulation and who were due to undergo OLT were randomized to receive either FFP or SDFFP. They were assessed for side effects, correction of coagulopathy, and seroconversion for viral markers. Results: Patients undergoing OLT showed equal correction of clotting factors and partial thromboplastin time (PTT) when treated with FFP or SDFFP. There was also a similar time course to return to baseline values in each group. There was no significant difference in correction of INR in either group. Usage of other blood components during the operation was identical in the two groups. No seroconversions were seen for HIV, HBC or HCV but only 12 patients were available for long term follow-up. Conclusion: SDFFP is an efficacious and safe source of coagulation factors for patients with liver disease undergoing Orthotopic Liver Transplantation. No adverse effects were seen during its administration. Further work is required to ascertain long term possibilities of seroconversion.

Abstract 1 Background The effectiveness of prophylactic platelets (plts) to prevent bleeding in patients with hematological malignancies remains unclear. The aim of this trial was to test the hypothesis that a policy of no-prophylactic plt transfusions (PltTx) is as effective and safe as a policy of prophylactic PltTx. Methods TOPPS was a randomized, parallel group, open-label, non-inferiority trial that recruited from 14 UK and Australian hospitals (ISRCTN08758735). The primary outcome was proportion of patients with a clinically significant bleed, defined as ≥WHO Grade 2, up to 30 days (d) from randomization. Non-inferiority margin was defined as a 15% difference in proportion of patients experiencing the primary outcome. Adult patients were eligible if they had a hematological malignancy, were receiving chemotherapy or stem cell transplant (SCT) and expected to be thrombocytopenic for at least 5 days. Patients were randomized by centralized computer system to receive either prophylactic PltTx if plt count was Results Recruitment began August 2006 and closed in August 2011. Of 1093 patients screened, 600 patients were randomized (301 no-prophylaxis, 299 prophylaxis). Baseline characteristics were well matched. 70% patients in both arms received autologous SCT (autoSCT). The majority of patients in both arms had complete bleeding data recorded [median 30d (IQR 29 to 30) no-prophylaxis arm, median 30d (IQR 30 to 30) prophylaxis arm]. Two patients (1 in each arm) withdrew prior to any data collection. Most PltTx in both arms were given according to protocol (no-prophylaxis 450/504 (89%) vs prophylaxis 810/894 (91%). Fewer patients in the no-prophylaxis group received PltTx (176/300, 59%) vs. prophylaxis group (266/298, 89%) [OR 0.14 (95% CI 0.09 to 0.23]; and they also received fewer PltTx overall [no-prophylaxis mean 1.7 PltTx (SD 2.6) vs. prophylaxis mean 3.0 PltTxs (SD 3.2); rate ratio 0.62, 95% CI 0.51 to 0.74]. Average number of days with plt count A WHO grade 2–4 bleed occurred in 151/300 patients (50%) in the no-prophylaxis group compared to 128/298 (43%) in the prophylaxis group (adjusted difference in proportions 8.4%, 90% CI 1.7 to 15.2%: p-value for non-inferiority 0.06). This study therefore did not prove its main aim, that a no-prophylaxis policy is non-inferior to prophylaxis. The time to the first grade 2–4 bleed was significantly shorter in the no-prophylaxis group (Fig. 1). Patients in the no-prophylaxis group averaged 1.7d (SD 2.9) with a WHO grade 2–4 bleed during follow-up, vs. 1.2d (SD 2.0) in the prophylactic group [rate ratio 1.52, 95% CI 1.14 to 2.03]. Whilst there were more grade 3–4 bleeds in the no-prophylaxis group (6/300) compared to the prophylaxis group (1/298) this did not reach statistical significance (OR 6.05, 95% CI 0.73 to 279.72, p = 0.13). Only 2 of these 7 patients had a plt count For all patients, there was no significant difference between treatment groups in period of thrombocytopenia, number of days in hospital, or number of SAEsexperienced. Discussion This multicenter study has not shown that a no-prophylaxis PltTx policy is non-inferior to prophylaxis. Patients in the no-prophylaxis group had more days with a WHO grade 2 or above bleed, and a shorter time to first bleed. Further analysis is needed to determine whether these findings apply to all subgroups of patients. Despite a role for prophylactic platelet transfusions, rates of bleeding in patients remain high. Funding NHS Blood and Transplant & Australian Red Cross Blood Service Disclosures: No relevant conflicts of interest to declare.