Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury.

BACKGROUND: Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS: The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS: In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.

Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial.

BACKGROUND: No randomised trials have addressed whether exposure to red blood cells (RBCs) stored longer than 35 days is associated with harm in patients. We aimed to assess the risk of in-hospital mortality associated with transfusing blood stored longer than 35 days. METHODS: We did a secondary analysis of the INforming Fresh versus Old Red cell Management (INFORM) trial, a pragmatic, multicentre, randomised controlled trial of patients (≥18 years) admitted to one of six hospitals in Australia, Canada, Israel, and the USA and expected to need RBC transfusions. Patients were randomly assigned (2:1) to receive blood in inventory stored for the longest time (standard care) or the shortest time, using a random allocation schedule and stratified by centre and patient ABO blood group. The primary objective of the INFORM trial was to assess all-cause in-hospital mortality in patients with blood group A and O who were transfused. For our exploratory secondary analysis, we classified individuals into one of three mutually exclusive exposure categories on the basis of the maximum storage duration of any blood unit patients had received on each day in hospital: exclusively exposed to RBCs stored no longer than 7 days, exposed to at least one unit of RBCs stored 8-35 days, and exposed to least one unit of RBCs stored longer than 35 days. Our primary objective was to determine the effect on risk of in-hospital death of time-dependent exposure to RBCs stored longer than 35 days compared with exclusive exposure to RBCs stored no longer than 7 days, both in patients of blood groups A and O and all patients. The INFORM trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN08118744. FINDINGS: Between April 2, 2012, and Oct 21, 2015, 31 497 patients were recruited, and 24 736 patients were eligible for inclusion in this analysis. We excluded nine patients for whom information about the storage duration of transfused blood was missing and one patient whose sex was unknown. 4480 (18%) patients were exposed to RBCs with longest storage, 1392 (6%) patients were exposed exclusively to RBCs with shortest storage, and 18 854 (76%) patients were exposed to RBCs stored 8-35 days. Median follow-up was 11 days (IQR 6-20). Exposure to RBCs stored longer than 35 days was not associated with increased risk of in-hospital death compared with exclusive exposure to the freshest RBC units after adjusting for demographic variables, diagnosis category, and blood product use history (in patients with blood group A or O: hazard ratio 0·94, 95% CI 0·73-1·20, p=0·60; in all patients: 0·91, 0·72-1·14, p=0·40). The risk of in-hospital death also did not differ between patients exposed to blood stored 8-35 days and patients exposed to blood stored 7 days or less (in patients with blood group A or O: 0·92, 0·74-1·15, p=0·48; in all patients: 0·90, 0·73-1·10, p=0·29). INTERPRETATION: These data provide evidence that transfusion of blood stored for longer than 35 days has no effect on in-hospital mortality, which suggests that current approaches to blood storage and inventory management are reasonable. FUNDING: Canadian Institutes for Health Research, Canadian Blood Services, and Health Canada.

Rationale and Design of the Informing Fresh versus Old Red Cell Management (INFORM) Trial: An International Pragmatic Randomized Trial.

Although red blood cell transfusion is a potentially lifesaving intervention in severely anemic and acutely bleeding patients, some observational studies have suggested that prolonged red cell storage before transfusion is associated with harm. INFORM is a large, pragmatic, randomized controlled trial comparing the effect of the shorter storage with longer storage red blood cell transfusions on inhospital mortality in hospitalized patients who require a blood transfusion. The trial is being conducted in centers in Australia, Canada, Israel, and the United States and is expected to enroll 31497 patients. If the results of INFORM indicate that shorter storage red blood cell transfusion is associated with superior outcomes compared with standard issue red blood cell transfusion, consideration may be given to shortening blood storage times. If, in contrast, the INFORM trial provides no evidence of harm from longer storage red blood cells, clinicians and patients may be reassured that current blood inventory management strategies are appropriate.

Senescence in amniocytes and placentas from trisomy 21 pregnancies.

OBJECTIVE: Senescence has been described as a stable cell proliferation arrest resulting from the progression of primary human fibroblasts through a finite number of population doublings in vitro. Accelerated telomere shortening was observed in pregnancies complicated by intrauterine growth restriction, in placentas of diabetic mothers and trisomy 21 amniocytes. We hypothesized that under conditions of stress, telomeres in placentas will be shorter and there will be more cells with the senescence phenotype. METHODS: The two study groups included placental biopsies from 7 cases of trisomy 21 and amniocytes from 10 cases of trisomy 21. The control groups consisted of placental biopsies from 6 cases and amniocytes from 10 pregnancies with a normal karyotype. The samples were analyzed for the presence of senescent cells based on the number of fragments in each cell. RESULTS: A significantly higher percentage of cells in the senescent state, based on a higher percentage of cells with more fragmentations, were found in the amniocytes (20.8%) and in trophoblasts (94.3%) from placentas with trisomy 21 compared to the control groups. CONCLUSION: Among other genetic instability parameters, trisomy 21 amniocytes and trophoblasts express a higher prevalence of senescent cells than were previously reported.