Christopher P. Stowell

Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery

BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

A prospective, randomized clinical trial of universal WBC reduction.

BACKGROUND : Recipient exposure to allogeneic donor WBCs results in transfusion complications for selected populations of recipients. Whether or not WBC reduction should be universally applied is highly controversial.

Progress in the development of RBC substitutes.

Volume 41, February 2001 TRANSFUSION 287 www.transfusion.org Considerable progress has been made in the development of RBC substitutes in the last decade, with several preparations advancing from the preclinical stage of testing to Phase III clinical trials. Although the primary focus has been on the development of a pharmacologic substitute that could carry and deliver oxygen (O2) in the place of banked blood, the unique properties of the RBC substitutes under study have led to the exploration of applications beyond the conventional use of RBCs in transfusions. The term “RBC substitute,” although widely used (including in medical literature databases), does not convey the diverse properties of, and potential clinical applications for, these materials. The availability of O2-carrying therapeutic agents for clinical use could have a significant impact on the practice of blood banking and transfusion medicine. This review describes the various substitutes under development and the progress that has been made in clinical trials, and considers some of the potential implications of their use. Several recent comprehensive reviews provide additional details regarding the scientific progress in developing these new products.1-6 RBCs have several unique properties. First, they contain a very high concentration of Hb and protect it from degradation, which would be rapid if the Hb were free in the plasma. Second, since Hb is contained within the cell, it does not come in direct contact with tissues, where it might otherwise release its heme and damage the tissue. Third, the intraerythrocytic environment prevents oxidation of Hb to methemoglobin, which is not capable of transporting O2 and may promote injurious oxidative reactions. 7

Therapy for paraneoplastic neurologic syndromes in six patients with protein a column immunoadsorption

Background. Paraneoplastic neurologic syndromes, although rare, cause significant morbidity and mortality. They are thought to be immunologically mediated, but to date those involving the central nervous system (CNS) have not been particularly responsive to immunologic therapy. The use of the novel immunomodulator, protein A immunoadsorption, was explored to address this question.

Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia: The TOTAL Randomized Clinical Trial

IMPORTANCE Although millions of transfusions are given annually worldwide, the effect of red blood cell (RBC) unit storage duration on oxygen delivery is uncertain. OBJECTIVE To determine if longer-storage RBC units are not inferior to shorter-storage RBC units for tissue oxygenation as measured by reduction in blood lactate levels and improvement in cerebral tissue oxygen saturation among children with severe anemia. DESIGN, SETTING, AND PARTICIPANTS Randomized noninferiority trial of 290 children (aged 6-60 months), most with malaria or sickle cell disease, presenting February 2013 through May 2015 to a university-affiliated national referral hospital in Kampala, Uganda, with a hemoglobin level of 5 g/dL or lower and a lactate level of 5 mmol/L or higher. INTERVENTIONS Patients were randomly assigned to receive RBC units stored 25 to 35 days (longer-storage group; n = 145) vs 1 to 10 days (shorter-storage group; n = 145). All units were leukoreduced prior to storage. All patients received 10 mL/kg of RBCs during hours 0 through 2 and, if indicated per protocol, an additional 10 mL/kg during hours 4 through 6. MAIN OUTCOMES AND MEASURES The primary outcome was the proportion of patients with a lactate level of 3 mmol/L or lower at 8 hours using a margin of noninferiority equal to an absolute difference of 25%. Secondary measures included noninvasive cerebral tissue oxygen saturation during the first transfusion, clinical and laboratory changes up to 24 hours, and survival and health at 30 days after transfusion. Adverse events were monitored up to 24 hours. RESULTS In the total population of 290 children, the mean (SD) presenting hemoglobin level was 3.7 g/dL (1.3) and mean lactate level was 9.3 mmol/L (3.4). Median (interquartile range) RBC unit storage was 8 days (7-9) for shorter storage vs 32 days (30-34) for longer storage without overlap. The proportion achieving the primary end point was 0.61 (95% CI, 0.52 to 0.69) in the longer-storage group vs 0.58 (95% CI, 0.49 to 0.66) in the shorter-storage group (between-group difference, 0.03 [95% CI, -0.07 to ∞], P < .001), meeting the prespecified margin of noninferiority. Mean lactate levels were not statistically different between the 2 groups at 0, 2, 4, 6, 8, or 24 hours. Kaplan-Meier analysis and global nonlinear regression revealed no statistical difference in lactate reduction between the 2 groups. Clinical assessment, cerebral oxygen saturation, electrolyte abnormalities, adverse events, survival, and 30-day recovery were also not significantly different between the groups. CONCLUSIONS AND RELEVANCE Among children with lactic acidosis due to severe anemia, transfusion of longer-storage compared with shorter-storage RBC units did not result in inferior reduction of elevated blood lactate levels. These findings have relevance regarding the efficacy of stored RBC transfusion for patients with critical tissue hypoxia and lactic acidosis due to anemia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01586923.

An Open-Label, Randomized Study to Compare the Safety and Efficacy of Perioperative Epoetin alfa With Preoperative Autologous Blood Donation in Total Joint Arthroplasty

A multicenter, randomized, open-label, parallel-group study was conducted to compare the safety and efficacy of perioperative recombinant human erythropoietin (Epoetin alfa) with the safety and efficacy of preoperative autologous donation (PAD) in total joint arthroplasty. A total of 490 patients scheduled for total joint (i.e., hip or knee) surgery and having hemoglobin (Hb) levels > or = 11 to < or = 13 g/dL were randomized to receive weekly doses of subcutaneous Epoetin alfa on preoperative Days -21, -14, and -7, and on the day of surgery, or to participate in a PAD program. The mean baseline Hb level in both groups was 12.3+/-0.6 g/dL, increasing to 13.8 g/dL in the Epoetin alfa-treated group and decreasing to 11.1 g/dL in the PAD group before or on the day of surgery. In the PAD group, 156/219 (71.2%) patients were transfused with autologous blood, and 42/219 (19.2%) patients were transfused with allogeneic blood. A smaller proportion, 27/209 (12.9%) patients, in the Epoetin alfa-treated group were transfused with allogeneic blood (P = .078 compared with the PAD group). Moreover, patients in the PAD group received a total of 325 units of blood (79 allogeneic units and 246 autologous units) compared with patients in the Epoetin alfa group who received a total of 54 units of blood. The mean postoperative Hb level was 11.0 g/dL in the Epoetin alfa-treated group and 9.2 g/dL in the PAD group. Compared with the PAD arm, mean Hb levels measured preoperatively, postoperatively on Day 1, and at discharge visits were significantly greater in the Epoetin alfa-treated arm (P < .0001 ).

Testing only donors with a prior history of pregnancy or transfusion is a logical and cost-effective transfusion-related acute lung injury prevention strategy.

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related fatality reported to the Food and Drug Administration. Donor screening may reduce TRALI risk. This study sought to compare the efficacy and safety of different TRALI risk‐reduction strategies at a hospital‐based donor center.

Light‐chain removal by plasmapheresis in myeloma‐associated renal failure

BACKGROUND: Although plasmapheresis has been recommended to reverse nephrotoxic elevations of serum free light chains (sFLCs), there are scant published data on removal of sFLC measured with modern assays.

Does red blood cell storage affect clinical outcome? When in doubt, do the experiment

Q uestions about the efficacy, safety, and availability of blood products are major concerns facing the FDA and the National Heart, Lung, and Blood Institute (NHLBI) as well as health care providers and administrators at hospitals. One of the basic questions that has been posed episodically but repeatedly for decades has been whether or not the changes that occur in red blood cells (RBCs) during storage affect clinical outcomes. Although the urgency of the question has waxed and waned over the years, it remains unanswered. This issue of TRANSFUSION offers two articles that address this issue. Lelubre and coauthors review our current level of understanding of the impact of RBC storage on patient outcomes and point out some of the difficulties of interpreting the data from these clinical studies. The clinical design feasibility study of Bennett-Guerrero and coauthors highlights some of the challenges of conducting definitive clinical trials in this area. Together, they help us focus on the direction we need to move, to address the questions that persist about the clinical impact of RBC storage._02265 1286..1290

A touch of TRALI.

Transfusion‐related acute lung injury (TRALI) is a leading cause of transfusion‐associated morbidity and mortality. The National Heart, Lung, and Blood Institute (NHLBI) and Canadian Consensus Conference definitions of TRALI exclude cases of mild TRALI. As a result, many cases of mild TRALI are likely to be missed. Three cases are reported in which patients experienced the acute onset of breathlessness in association with transfusion of blood components containing human leukocyte antigen (HLA) antibodies reactive with recipient HLA antigens. Despite the sudden onset of a pulmonary syndrome in association with transfusion, clinicians caring for these patients did not consider TRALI, and no case would meet recent consensus definitions. Nevertheless, supporting clinical and serologic evidence for TRALI was found in each case. Benefits in recognizing mild cases of TRALI include quantifying the true incidence of TRALI, understanding the physiology of mild versus severe TRALI, and preventing subsequent cases of TRALI due to donors found to have HLA antibodies.