Rebecca Barty

A randomized controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia

A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 x 10(9) platelets/product) or low-dose (150- < 300 x 10(9) platelets/product) platelets. The primary outcome (World Health Organization [WHO] bleeding > or = grade 2) was assessed daily through clinical examination, patient interview, and chart review. A WHO grade was assigned through adjudication. The Data Safety Monitoring Board stopped the study because the difference in the grade 4 bleeding reached the prespecified threshold of 5%. At this time, 129 patients had been randomized and 119 patients were included in the analysis (58 low dose; 61 standard dose). Three patients in the low-dose arm (5.2%) had grade 4 bleeds compared with none in the standard-dose arm. WHO bleeding grade 2 or higher was 49.2% (30/61) in the standard-dose arm and 51.7% (30/58) in the low-dose group (relative risk [RR], 1.052; 95% confidence interval [CI], 0.737-1.502). A higher rate of grade 4 bleeding in patients receiving low-dose prophylactic platelet transfusions resulted in this RCT being stopped. Whether this finding was due to chance or represents a real difference requires further investigation. These clinical studies are registered on (http://www.clinicaltrials.gov) as NCT00420914.

Perioperative Management of Dabigatran: A Prospective Cohort Study

Background— The perioperative management of dabigatran in clinical practice is heterogeneous. We performed this study to evaluate the safety of perioperative management of dabigatran using a specified protocol. Methods and Results— Patients treated with dabigatran and planned for an invasive procedure were eligible for inclusion. The timing of the last dose of dabigatran before the procedure was based on the creatinine clearance and procedure-related bleeding risk. Resumption of dabigatran was prespecified according to the complexity of the surgery and consequences of a bleeding complication. Patients were followed up for 30 days for major bleeding (primary outcome), minor bleeding, arterial thromboembolism, and death. We included 541 cases: 324 procedures (60%) with standard risk of bleeding and 217 procedures (40%) with increased risk of bleeding. The last dose of dabigatran was at 24, 48, or 96 hours before surgery according to the protocol in 46%, 37%, and 6%, respectively, of the patients. Resumption was timed according to protocol in 77% with 75 mg as the first dose on the day of procedure in 40% of the patients. Ten patients (1.8%; 95% confidence interval, 0.7–3.0) had major bleeding, and 28 patients (5.2%; 95% confidence interval, 3.3–7.0) had minor bleeding events. The only thromboembolic complication was transient ischemic attack in 1 patient (0.2%; 95% confidence interval, 0–0.5), and there were 4 deaths unrelated to bleeding or thrombosis. Bridging was not used preoperatively but was administered in 9 patients (1.7%) postoperatively. Conclusion— Our protocol for perioperative management of dabigatran appears to be effective and feasible. # CLINICAL PERSPECTIVE {#article-title-21}Background— The perioperative management of dabigatran in clinical practice is heterogeneous. We performed this study to evaluate the safety of perioperative management of dabigatran using a specified protocol. Methods and Results— Patients treated with dabigatran and planned for an invasive procedure were eligible for inclusion. The timing of the last dose of dabigatran before the procedure was based on the creatinine clearance and procedure-related bleeding risk. Resumption of dabigatran was prespecified according to the complexity of the surgery and consequences of a bleeding complication. Patients were followed up for 30 days for major bleeding (primary outcome), minor bleeding, arterial thromboembolism, and death. We included 541 cases: 324 procedures (60%) with standard risk of bleeding and 217 procedures (40%) with increased risk of bleeding. The last dose of dabigatran was at 24, 48, or 96 hours before surgery according to the protocol in 46%, 37%, and 6%, respectively, of the patients. Resumption was timed according to protocol in 77% with 75 mg as the first dose on the day of procedure in 40% of the patients. Ten patients (1.8%; 95% confidence interval, 0.7–3.0) had major bleeding, and 28 patients (5.2%; 95% confidence interval, 3.3–7.0) had minor bleeding events. The only thromboembolic complication was transient ischemic attack in 1 patient (0.2%; 95% confidence interval, 0–0.5), and there were 4 deaths unrelated to bleeding or thrombosis. Bridging was not used preoperatively but was administered in 9 patients (1.7%) postoperatively. Conclusion— Our protocol for perioperative management of dabigatran appears to be effective and feasible.

Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis.

The impact of transfusing fresher vs older red blood cells (RBCs) on patient-important outcomes remains controversial. Two recently published large trials have provided new evidence. We summarized results of randomized trials evaluating the impact of the age of transfused RBCs. We searched MEDLINE, EMBASE, CINAHL, the Cochrane Database for Systematic Reviews, and Cochrane CENTRAL for randomized controlled trials enrolling patients who were transfused fresher vs older RBCs and reported outcomes of death, adverse events, and infection. Independently and in duplicate, reviewers determined eligibility, risk of bias, and abstracted data. We conducted random effects meta-analyses and rated certainty (quality or confidence) of evidence using the GRADE approach. Of 12 trials that enrolled 5229 participants, 6 compared fresher RBCs with older RBCs and 6 compared fresher RBCs with current standard practice. There was little or no impact of fresher vs older RBCs on mortality (relative risk [RR], 1.04; 95% confidence interval [CI], 0.94-1.14; P = .45; I(2) = 0%, moderate certainty evidence) or on adverse events (RR, 1.02; 95% CI, 0.91-1.14; P = .74; I(2) = 0%, low certainty evidence). Fresher RBCs appeared to increase the risk of nosocomial infection (RR, 1.09; 95% CI, 1.00-1.18; P = .04; I(2) = 0%, risk difference 4.3%, low certainty evidence). Current evidence provides moderate certainty that use of fresher RBCs does not influence mortality, and low certainty that it does not influence adverse events but could possibly increase infection rates. The existing evidence provides no support for changing practices toward fresher RBC transfusion.

The effect of blood storage duration on in-hospital mortality: a randomized controlled pilot feasibility trial

BACKGROUND: Whether the duration of storage of blood has an impact on patient outcomes remains controversial. The objective was to determine feasibility of a comparative effectiveness trial to evaluate duration of storage of blood before transfusion on in‐hospital mortality.

Red blood cell processing methods and in-hospital mortality: a transfusion registry cohort study

BACKGROUND Quality of red blood cells (RBCs) varies depending on the method of processing the whole blood donation, and the method of processing might affect outcomes in patients transfused RBCs. We aimed to establish whether an association exists between in-hospital mortality and RBC processing method and duration of storage. METHODS We did a retrospective registry cohort study using data from three acute care hospitals in Hamilton, ON, Canada, and Canadian Blood Services over a 6-year period (2008-14). Adult patients (≥18 years) who were admitted to hospital and who received RBC transfusions were included in the study. All transfused RBCs were characterised by the method of processing (red cell filtered or whole blood filtered) and storage age (fresh 1-7 days, mid 8-35 days, and old 36-42 days). The primary outcome was in-hospital mortality. We used Cox proportional hazards regression with time-dependent stratification variables and fixed stratification variables, and controlled for patient covariates. FINDINGS Between April 1, 2008, and March 31, 2014, 91 065 RBC transfusions were given to 23 634 adults who were included in the analyses. When storage duration was included in the model, in-hospital mortality was significantly increased with fresh whole blood filtered units compared with the reference group of mid-age red cell filtered units (hazard ratio 2·19, 95% CI 1·09-4·42; p=0·033). Differences between other age and processing categories were not significant. INTERPRETATION The potential effect of whole blood processing methods on patient outcomes is worthy of further investigation, since adverse outcomes could be reduced by minor changes to blood processing methods and inventory management policies. FUNDING Canadian Blood Services, Health Canada, and the Canadian Institutes of Health Research.

Factors affecting the frequency of red blood cell outdates: an approach to establish benchmarking targets.

BACKGROUND: Benchmarking is a useful tool to identify best practices and to compare an organizations performance with that of similar peers, allowing for continuous quality improvement. In this study, a provincial database of red blood cell (RBC) product inventory/disposition in hospitals was analyzed to identify factors that affected RBC outdates and to systematically establish optimal target levels for RBC outdates.

In vitro evaluation of prestorage pooled leukoreduced whole blood–derived platelets stored for up to 7 days

BACKGROUND: Advantages to storing whole blood–derived platelets (PLTs) as a pool for 7 days would include operational efficiencies and facilitation of bacterial testing and pathogen inactivation. The in vitro quality of pre‐storage pooled PLTs stored for up to 7 days was assessed.

Assessing the effectiveness of whole blood–derived platelets stored as a pool: a randomized block noninferiority trial

BACKGROUND: Prestorage pooling of whole blood–derived platelets (PLTs) would simplify bacterial detection. This study evaluated the in vivo effect of the prestorage pooling of PLTs stored for up to 5 days, by assessing the corrected count increment (CCI) 18 to 24 hours after transfusion of the product.

Effect of standardized perioperative dabigatran interruption on the residual anticoagulation effect at the time of surgery or procedure.

Essentials Anticoagulants need to be stopped preprocedure so there is little or no remaining anticoagulant effect. We assessed the residual anticoagulant effect with standardized interruption for patients on dabigatran. With this protocol, 80–86% of patients had no residual anticoagulant effect at the time of a procedure. A standardized perioperative dabigatran protocol appears to be safe, but requires further study.

Exploratory studies on the age of transfused blood and in-hospital mortality in patients with cardiovascular diagnoses.

The objective was to examine the association between blood storage duration and in‐hospital mortality in a large cohort of cardiovascular patients transfused between 2002 and 2011.