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.).

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Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

SummaryPrevious studies have shown that total platelet count (TPC) inadequately predicts bleeding in thrombocytopenic patients with haematological malignancies. This prospective cohort study evaluated whether rotational thromboelastometry (ROTEM), coagulation or other platelet parameters were more strongly associated with bleeding than TPC. Adults treated at two UK haematology centres for haematological malignancy were enrolled if they had thrombocytopenia (TPC ≤ 50 9 10 9 /l) at beginning of, or during treatment (International Standard Randomized Controlled Trial Number 81226121). TPC and bleeding symptoms were recorded daily for up to 30 d or until platelet count recovery, hospital discharge or death. Blood samples were tested thrice weekly using ROTEM, Platelet Function Analyser (PFA)-100 â , coagulation and platelet cytometry assays. Bleeding symptoms and TPC from 49/50 enrolled participants who completed the study were recorded on 754/760 study days. Mean platelet volume and PFA-100 â closure times were frequently inestimatable because of thrombocytopenia. TPC, absolute immature platelet number (AIPN) and ROTEM maximum clot firmness were significantly associated with bleeding on the day after blood sampling. Only AIPN was associated with bleeding after adjustment of test results for TPC (Odds Ratio 0Á52, 95% confidence interval 0Á28-0Á97; P = 0Á038). In a predictive model, AIPN was superior to TPC for predicting bleeding. This study indicates that AIPN may be more clinically useful than TPC at predicting bleeding.

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 <10×109/L, or no prophylaxis. Allocated treatment policy applied for 30d from randomization, irrespective of in- or out-patient status. In both arms PltTx were given therapeutically (documented signs or symptoms of bleeding) or prior to invasive procedures or at physician discretion. Analysis was by intention to treat. 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 <10 and <20×109/L was significantly longer in no-prophylaxis arm. 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 <10×109/L at onset of grade 3–4 bleeding (median plt count 16, range 3–42 x109/L); both patients were receiving induction chemotherapy for AML. Pre-defined subgroup analysis between autoSCT vs other treatments for the primary outcome found a significant interaction (p-value 0.04). In the autoSCT group, WHO grade 2–4 bleed grade occurred in 99/210 patients (47%) in the no-prophylaxis group vs 95/210 (45%) in the prophylaxis group (difference in proportions 2.3%, 90% CI −5.7 to 10.3%). 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.