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.

Future of platelet formulations with improved clotting profile: a short review on human safety and efficacy data.

BACKGROUND: Platelet (PLT) transfusion is a widely used therapy in treating or preventing bleeding and hemorrhage in patients with thrombocytopenia or trauma. Compared to the relative ease of PLT transfusion, current practice for PLT storage at room temperature (RT) for up to 5 to 7 days is inefficient, costly, wasteful, and relatively unsafe. STUDY DESIGN AND METHODS: This study was a review of major advances in PLT derivative products with improved hemostatic potential and safety feature. RESULTS: Recent progress in understanding the PLT activation and host clearance mechanisms has led to reassessments of current and new storage conditions that employ refrigeration and/or cryopreservation to overcome storage lesions and significantly extend shelf life of PLTs with reduced risk of pathogen contamination. DISCUSSION: It is anticipated that future PLT preservation involving cold, frozen, and/or pathogen reduction strategies in proper PLT additive solutions will enable longer term and safer PLT storage.

The evolving role of lyophilized plasma in remote damage control resuscitation in the French Armed Forces Health Service.

Freeze-dried plasma was developed by the US Army for the resuscitation of combat casualties during World War II. The French Military Blood Institute began producing French lyophilized plasma (FLYP) in 1949, in accordance with French blood product guidelines. Since 2010, a photochemical pathogen inactivation process has been implemented to reduce the remaining transfusion-related infectious risk. All quality controls for this procedure verify that the hemostatic properties of FLYP are conserved. FLYP is compatible with all blood types, can be stored at room temperature for 2 years, and its reconstitution requires less than 6 minutes. As a result, FLYP allows quick delivery of all the coagulation proteins and the application of a 1:1 ratio of FLYP and red blood cells in the context of a massive transfusion. Hemovigilance data collected in France since 1994 have included FLYP. Results indicate no reporting of infection related to the use of FLYP. Clinical monitoring with a focus on hemostasis was implemented in 2002 and expanded in 2010. The data, obtained from overseas operations, confirmed the indications, the safety and the clinical efficacy of FLYP. Further research is needed to determine specific indications for FLYP in the therapeutic management of civilian patients with severe hemorrhage.

Relationship between red cell storage duration and outcomes in adults receiving red cell transfusions: a systematic review.

INTRODUCTION: The duration of red blood cell (RBC) storage before transfusion may alter RBC function and supernatant and, therefore, influence the incidence of complications or even mortality. METHODS: A MEDLINE search from 1983 to December 2012 was performed to identify studies reporting age of transfused RBCs and mortality or morbidity in adult patients. RESULTS: Fifty-five studies were identified; most were single-center (93%) and retrospective (64%), with only a few, small randomized studies (eight studies, 14.5%). The numbers of subjects included ranged from eight to 364,037. Morbidity outcomes included hospital and intensive care unit (ICU) length of stay (LOS), infections, multiple organ failure, microcirculatory alterations, cancer recurrence, thrombosis, bleeding, vasospasm after subarachnoid hemorrhage, and cognitive dysfunction. Overall, half of the studies showed no deleterious effects of aged compared to fresh blood on any endpoint. Eleven of twenty-two (50%) studies reported no increased mortality, three of nine (33%) showed no increased LOS with older RBCs and eight of twelve (66%) studies showed no increased risks of organ failure. Ten of eighteen (55%) studies showed increased infections with transfusion of older RBCs. The considerable heterogeneity among studies and numerous methodological flaws precluded a formal meta-analysis. CONCLUSIONS: In this systematic review, we could find no definitive argument to support the superiority of fresh over older RBCs for transfusion.

Perspectives of potential donors on cord blood and cord blood cryopreservation: a survey of highly educated, pregnant Korean women receiving active prenatal care.

BACKGROUND: The aim of the study was to investigate the knowledge of cord blood (CB) and attitudes toward CB banking among high-potential donors (i.e., well-educated pregnant Koreans) because their voluntary donation is indispensable to the success of unrelated CB transplantation. STUDY DESIGN AND METHODS: Questionnaires examining perspectives on CB were distributed to and completed by 1001 women attending a maternity education program from April to October 2008; 863 women answered that they had heard of CB. We analyzed the 863 questionnaires to identify the sources of information, the plan for CB, the reasons for decisions, beliefs about the potential uses of CB, and knowledge about current therapeutic uses. RESULTS: Most subjects received information from promotional materials distributed by CB banks and the media; however, minimal information was obtained from obstetricians. More than 90% of women who planned to donate cited "altruism," and 75.0% of the "private preservation" group indicated that a desire to "safeguard for the future" was the reason for their decision. The probability of autologous CB transplantation (p = 0.001) and current usefulness were significantly overestimated in the private preservation group (p = 0.02). In addition, 56% of subjects underestimated the probability of identifying a matched CB in the public bank, and the overall rate of correct answers about current usefulness was 57.4%. CONCLUSIONS: A considerable portion of educated pregnant Korean women has more than minimal knowledge of CB, but the levels of knowledge regarding the potency of the public bank and the current usefulness and limitations of CB are generally low; in addition, obstetricians play insignificant roles in disseminating knowledge. Providing accurate and detailed information to pregnant women not only via brochures and the media and/or Internet but also by obstetricians would encourage CB donation.

Frozen Platelets-Development and Future Directions.

Storage requirements and outdating of platelets represent a continued challenge for blood banks. These hurdles are confounded for rural area hospitals or in military deployments. Over 60 years of research and development into frozen platelets have generated a stable and reproducible product. Valeri's method to freeze platelets in 6% dimethyl sulfoxide (DMSO) and storage at -80°C allows for long-term storage alleviating burdens placed on blood banks. Clinical studies show that frozen platelet transfusions are safe with no related thrombotic or other serious adverse events. There are ongoing efforts to demonstrate cryopreserved platelet (CPP) superiority in efficacy studies designed in trauma or cardiac surgery patients. Technical advances in CPP manufacturing including closed system manufacturing, applications of pathogen reduction technology and potency standard characterization add to the appeal of CPP as an alternative to traditional liquid-stored platelets (LP) in settings of supply shortages, mass casualty, active bleeding, rapid provision of HLA-compatible platelets, and remote care.

Past and future approaches to assess the quality of platelets for transfusion.

No automated test exists to routinely measure platelet quality. Currently, the short, 5-day shelf life of platelet concentrates is largely dictated by the risk associated with bacterial contamination and not by platelet quality. With the implementation of bacterial testing and pathogen inactivation, platelet quality will become the major determinant for the shelf life of platelet concentrates. However, extended use of platelet concentrates stored beyond 5 days will require quality testing. In addition, high platelet quality would be expected to result in improved clinical efficacy, determined by count increment, improved hemostasis, and lower risk for adverse reactions in recipients. No in vitro quality test has yet demonstrated a good correlation with clinical efficacy or improved hemostasis. This review focuses on those tests of platelet quality that are based on platelet morphology. These include visual inspection of swirling, microscopic morphology score, measurement of light transmission through platelet concentrates, and platelet light scattering techniques. Recently, a new test for platelet quality has been introduced that uses dynamic light scattering. The advantages and remaining challenges for dynamic light scattering before it can become a routine platelet quality test are discussed.

Research Progress of Platelet Transfusion in China.

Platelet products have been increasingly used for more than 50 years. Platelet transfusion is effective for correcting bleeding caused by thrombocytopenia and platelet function defects. In this review, we will outline research on platelet transfusion in China including platelet biosafety, cryopreservation of platelets, the assessment of the effectiveness of platelet transfusion, the causes of platelet transfusion refractoriness including immunization against CD36, and neonatal alloimmune thrombocytopenia.

The new generation of platelet additive solution for storage at 22 degrees C: development and current experience.

The storage of platelets (PLTs) in PLT additive solutions (PASs) might have several advantages. It can reduce allergic and febrile transfusion reactions, facilitate AB0-incompatible PLT transfusions, enable pathogen inactivation, and make more plasma available for other purposes (eg, for fractionation). For this reason, there has been considerable focus on the development of new PASs that assure maintenance of good PLT quality throughout storage. Several compounds in PASs such as citrate, acetate, phosphate, potassium, and magnesium have all turned out to be important, and the same applies to the necessary amount of glucose as determined by the plasma carryover. The latest generation of PASs, the modified PAS-III and Composol-PS, contains most or all of those compounds. Recently published data on the in vitro quality of either buffy coat- or apheresis-derived PLT concentrates stored in 70% or even 80% of PAS might encourage transfusion specialists to consider using these PASs in routine blood banking. However, because in vitro tests do not adequately predict clinical effectiveness of PLTs after transfusion, in vivo studies are still needed to assess the quality of PAS-stored PLTs.

The future of automated red blood cell collection.

Automated red blood cell (RBC) collection is a newer but well-established form of donor apheresis. The technologies comprising and supporting apheresis have undergone significant advancements through the past 50 years, and we anticipate further improvements in devices and systems for automated RBC collection. Multiple factors must be considered in implementing automated RBC collections, but these procedures provide a way to draw additional RBC products that meet cGMP, regulatory, blood collector economic and donor objectives while maintaining or improving RBC availability. The continuing need for RBCs, accompanied by shrinking donor availability, would indicate that automated RBC collections will grow.

The Mirasol PRT system for pathogen reduction of platelets and plasma: an overview of current status and future trends.

The safety of blood transfusion is still threatened by contamination of blood products with a variety of pathogens such as viruses, bacteria and parasites. A novel pathogen reduction process for platelets and plasma products, the Mirasol PRT system, has been developed and is under clinical evaluation for its efficacy and safety. The Mirasol PRT process is based on riboflavin photochemistry. This manuscript reviews current progress and future trends.

Biopreservation of red blood cells: past, present, and future.

Preservation and long-term storage of red blood cells (RBCs) is needed to ensure a readily available, safe blood supply for transfusion medicine. Effective preservation procedures are required at various steps in the production of a RBC product including testing, inventory, quality control, and product distribution. Biopreservation is the process of maintaining the integrity and functionality of cells held outside the native environment for extended storage times. The biopreservation of RBCs for clinical use can be categorized based on the techniques used to achieve biologic stability and ensure a viable state after long-term storage. This paper will review the history, science, current practices, and emerging technologies of current RBC biopreservation approaches: hypothermic storage, cryopreservation, and lyophilization.

Multicomponent apheresis blood collection in the United States: current status and future directions.

Transfusion medicine in the USA confronts the ongoing challenges posed by a worsening blood supply, regulatory pressure, public pressure for increased safety and cost pressure. Multicomponent apheresis collection (MAC) is a powerful tool for addressing these issues. There are both clinical and operational advantages to MAC. The most important MAC procedures currently performed are platelet and two-red blood cell apheresis. Both procedures are growing in importance to the blood supply as the demand for platelets and red blood cells (RBC) increase. As the demand for safer and more standardized blood components increases, red cell apheresis may possibly become the collection standard.

What's happening? The expanding role of apheresis platelet support in neonatal alloimmune thrombocytopenia: current status and future trends.

Despite some unresolved problems that may be associated with platelet transfusion, such as alloimmunisation, refractoriness, bacterial contamination, and the potential side effects related to the development of some biological response modifiers during storage, platelet therapy remains the most effective treatment for the management and prevention of severe thrombocytopenia and hemorrhage [Seghatchian J, Snyder EL, Krailadsiri P, editors. Platelet therapy: current status and future trends. Amsterdam, The Netherlands: Elsevier; 2000]. This appears to be particularly the case in neonatal alloimmune thrombocytopenia (NAIT), which arises due to an incompatibility of the platelet specific antigens between the pregnant mother and her baby. Over 80% of severe NAIT cases in the Caucasian population occur when the mother and baby differ in their HPA-1 epitope (HPA-1a negative and positive respectively) leading, in 10% of cases, to the production of anti-HPA-1a which can cross the placenta and cause NAIT in utero or post-partum. Anti-HPA-5b is the second most cause of NAIT, although severe cases occur only after the first pregnancy. Clinical manifestations of NAIT vary from mild (petechia and bruises) to severe (intracranial haemorrhage with possible death or life long morbidity). A recent study in Scotland indicated that the cost per case of severe NAIT detected during screening of pregnant women, where anti-HPA-1a is detected for the first time, would amount to $98,771 [Turner M, Bessos H, et al. Prospective epidemiological study of the outcome and cost effectiveness of antenatal screening to detect neonatal alloimmune thrombocytopenia (NAIT) due to anti-HPA-1a. Transfusion, in press. Yet, unlike the case with Rhesus hemolytic disease of the new born, the cost-effectiveness of HPA-1 screening in NAIT remains unresolved, as does the most optimal mode of treatment. Therefore, in the absence of a consensus on the screening and optimal management of NAIT, the availability and provision of HPA-1a/5b negative apheresis platelets based on current practice (transfusionguidelines.org.uk) appear to be a clinically effective treatment in NAIT. In that vein, an increasing number of blood transfusion centres are screening blood donors in order to secure panels of donors for the prompt provision of HPA-1a/5b negative apheresis platelets. However, evidence is also accumulating that while platelets derived from various apheresis technologies currently in use may be equivalent in terms of cellular contents (thus meeting specifications), they may differ in terms of the platelet storage lesion, microvesiculation and the development of platelet-derived cytokines and some other biological response modifiers [Seghatchian J. Platelet storage lesion: the influence of various leukoreduction procedures on generation/retention of some biological response modifiers, microvesiculation, distribution of membrane-bound/soluble Prion and the rate of HLA-CLASS1 release. Trans Apher Sci, in press. This manuscript summarises strategy and progress both in the improvement of apheresis platelet quality and provision in NAIT.