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Objective Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. Design Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. Setting 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. Patients 660 infants born at less than 34 weeks’ gestation with platelet counts less than 50×109/L. Interventions Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). Main outcomes measures Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. Results Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). Conclusions Infants randomised to a higher platelet transfusion threshold of 50×109/L compared with 25×109/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. Trial registration number NCT87736839.

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 .).

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 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.).

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 x 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 x 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.

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.

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 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.

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.

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.