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Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Introduction and Objective: Intravenous iron preparations rapidly correct iron deficiency anemia, with the notable drug class effect of rare, yet potentially life-threatening, administration-related hypersensitivity or anaphylactic reactions. The objective of this comparative study was to assess adverse events associated with four intravenous iron preparations and estimated medical costs, in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database., Methods: Cases of hypersensitivity reactions and anaphylaxis/anaphylactic shock associated with iron dextran, iron sucrose, ferumoxytol, and ferric carboxymaltose, spontaneously reported to FAERS (1 January, 2014 to 31 December, 2019), were extracted. The reporting odds ratio lower bound 90% confidence interval (ROR05) > 1 and cases ≥ 5 defined a likely signal for a drug-adverse event association. Adverse event-associated medical costs were estimated using Agency for Healthcare Research and Quality/Healthcare Cost and Utilization Project 2016 data., Results: For hypersensitivity reactions, ferumoxytol and iron dextran had the highest ROR05 values (5.00 and 4.35, respectively) and greatest proportions of associated deaths (7.1% and 5.3%), followed by iron sucrose (ROR05 3.94, deaths 2.4%), and ferric carboxymaltose (ROR05 3.03, deaths 0.2%). For anaphylaxis/anaphylactic shock, ROR05 for cases/deaths were: 39.32/13.4%, ferumoxytol; 37.80/4.5%, iron dextran; 17.60/4.7%, iron sucrose; and 8.77/no deaths, ferric carboxymaltose. Downstream medical costs per adverse event were highest with iron dextran (US$8615) and ferumoxytol (US$8164), followed by iron sucrose (US$4212), and ferric carboxymaltose (US$1832)., Conclusions: Reporting rates of hypersensitivity and anaphylaxis with intravenous iron preparations were highest with ferumoxytol and lowest with ferric carboxymaltose in the US FAERS database. Adverse event-related medical costs were highest for iron dextran and ferumoxytol, and lowest for ferric carboxymaltose.

Anemia is a common finding in the perioperative setting with significant untoward consequences including worsening of outcomes and diminished quality of life as well as increased risk of allogeneic blood transfusions. Here, we present 3 cases that illustrate how anemia can be perioperatively managed in patients undergoing cardiac, orthopedic, and oncology surgeries. Timely detection of anemia prior to high-blood loss surgeries can allow clinicians to manage it and optimize hemoglobin level, making patients better prepared for the surgery. Treatment of anemia should be guided by the etiology and may include erythropoietic agents, folic acid, B12, and iron preparations. Other blood management strategies geared toward reducing surgical blood loss such as autologous transfusion techniques and agents to optimize hemostasis are used during surgery and in the immediate postoperative period. Patients should be closely monitored following surgery for signs of ongoing bleeding in need of control. Finally, screening for and management of anemia should continue in the postoperative and postdischarge period, as persistence and recurrence of anemia can further undermine patient's outcomes., (© 2020 by The American Society of Hematology.)

Objectives: Increasingly complex medical care requires specialized transfusion support close at hand. Hospital growth can necessitate expansion of blood bank services to new locations to ensure rapid delivery of blood products. We describe the opening of a new satellite transfusion service designed to serve the needs of a pediatric hospital., Methods: Institutional transition teams and stakeholders collaborated to discuss options for providing blood at a new pediatric hospital. A staffed satellite transfusion service met the diverse needs of multiple services and was considered a compromise between a full new transfusion service and automated solutions., Results: Initial challenges in establishing the laboratory included regulatory uncertainty and interactions between two hospitals' information technology services. Laboratory scientist staffing and actual use required adapting the satellite service to an emergency release-only model., Conclusions: A flexibly staffed satellite transfusion service met the most urgent needs of a pediatric hospital expansion. Review of implementation revealed potential process improvements for future expansions, including comprehensive routine and massive transfusion simulations. The challenges experienced in supplying staff and specialized blood products track with national trends. Other institutions may consider establishing a satellite transfusion service in the context of both increasingly sophisticated automated solutions and complex blood needs., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with chronic kidney disease (CKD) are at increased risk for infection, attributable to immune dysfunction, increased exposure to infectious agents, loss of cutaneous barriers, comorbid conditions, and treatment-related factors (eg, hemodialysis and immunosuppressant therapy). Because iron plays a vital role in pathogen reproduction and host immunity, it is biologically plausible that intravenous iron therapy and/or iron deficiency influence infection risk in CKD. Available data from preclinical experiments, observational studies, and randomized controlled trials are summarized to explore the interplay between intravenous iron and infection risk among patients with CKD, particularly those receiving maintenance hemodialysis. The current evidence base, including data from a recent randomized controlled trial, suggests that proactive judicious use of intravenous iron (in a manner that minimizes the accumulation of non-transferrin-bound iron) beneficially replaces iron stores while avoiding a clinically relevant effect on infection risk. In the absence of an urgent clinical need, intravenous iron therapy should be avoided in patients with active infection. Although serum ferritin concentration and transferrin saturation can help guide clinical decision making about intravenous iron therapy, definition of an optimal iron status and its precise determination in individual patients remain clinically challenging in CKD and warrant additional study., (© 2020 The Authors.)

Despite many years of published medical society guidelines for red blood cell (RBC) transfusion therapy, along with clinical trials that provide Level 1 evidence that restrictive transfusion practices can be used safely and are equivalent to transfusions given more liberally, annualized blood transfusion activity did not begin to decline in the United States until 2010. Adoption of electronic medical records has subsequently allowed implementation of clinical decision support (CDS): best practice alerts that can be initiated to improve the use of blood components. We describe our own institutional experience using a targeted CDS to promote restrictive blood transfusion practice and to improve RBC use. A 42% reduction in RBC transfusions was demonstrated at our institution from a baseline in 2008 through 2015, and the rate remained stable through 2018. Although the data cannot be used to infer causality, this decreased RBC use was accompanied by improved clinical outcomes., Competing Interests: Conflict-of-interest disclosure: L.T.G. and M.A.H. declare no competing financial interests., (© 2019 by The American Society of Hematology. All rights reserved.)

Objective: To perform a systematic review of randomized trials comparing oral vs intravenous (IV) iron therapy to treat postpartum anemia., Data Sources: Data sources were as follows: PubMed (1972-2017); Cochrane Central Register of Controlled Trials, CENTRAL (1972-2017); CINAHL (1972-2017); Web of Science; Excerpta Medica Database, and EMBASE (1972-2017)., Study Eligibility Criteria: We included randomized trials comparing oral vs IV iron monotherapy to treat postpartum anemia (classified as a hemoglobin <12 g/dL)., Study Appraisal and Synthesis Methods: Study quality was assessed with the Cochrane risk of bias assessment tool. The primary outcome was hemoglobin concentration at 6 weeks postpartum. Secondary outcomes included hemoglobin concentration at 1-5 weeks postpartum, ferritin concentration at 1-6 weeks postpartum, and maternal adverse outcomes. For meta-analysis, mean differences and odds ratios using a random effects model were calculated. Risk of heterogeneity was reported as I 2 ., Results: A total of 15 randomized trials met our inclusion criteria (n = 1001 and 1 181 women receiving oral iron and IV iron, respectively); 4 studies reported data for our primary outcome. We observed higher postpartum week 6 hemoglobin concentrations in the IV iron group compared to the oral iron group (mean difference, 0.9 g/dL; 95% confidence interval (CI), 0.4-1.3; P = .0003). Compared to oral iron, women receiving IV iron had higher hemoglobin concentrations at postpartum weeks 1, 2, and 3; higher ferritin concentrations at postpartum weeks 1, 2, 4, and 6; an increased likelihood of skin flushing (odds ratio [OR], 6.95; 95% CI, 1.56-31.03; P = .01; I 2  = 0%); and a decreased likelihood of constipation (OR, 0.08; 95% CI, 0.03-0.21; P < .00001, I 2  = 27%) and dyspepsia (OR, 0.07; 95% confidence interval, 0.01-0.42; P = .004; I 2  = 0%). The reported event rate for anaphylaxis among women receiving IV iron was 0.6%., Conclusion: In this systematic review, among women with postpartum anemia, hemoglobin concentrations at 6 weeks postpartum were almost 1 g/dL higher in women who received IV iron compared to oral iron. The safety profile of IV iron was also reassuring. Given the weaker hemoglobin response and higher risk of gastrointestinal side effects with oral iron use, our findings suggest that IV iron be considered as a viable treatment option for postpartum iron deficiency anemia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: CD47 is a novel therapeutic target in the treatment of solid-organ and hematologic malignancies. CD47 is also expressed on RBCs. Here, we report our experience of the RBC effects and the impact on blood bank testing and transfusion management in a Phase 1 trial of the humanized anti-CD47 monoclonal antibody Hu5F9-G4 in relapsed or primary refractory acute myeloid leukemia (AML) (NCT02678338)., Study Design and Methods: Nineteen patients with relapsed or primary refractory AML treated across five UK centers were included for analysis. Patients received escalating doses of Hu5F9-G4. Serial laboratory data were collected to evaluate impact on hemoglobin (Hb), markers of hemolysis (bilirubin, lactate dehydrogenase, reticulocyte count), transfusion requirements, and blood compatibility testing., Results: A decline in Hb was observed with drug administration (median Hb change, -1.0 g/dL; range, 0.4-1.6) with associated increase in transfusion requirements. Patients responded to transfusion with a median Hb increment per unit of 1.0 g/dL. RBC agglutination was seen in all cases without associated change in Hb, lactate dehydrogenase, bilirubin, or reticulocyte count. Nine of 19 (47%) patients developed a newly positive antibody screen with a pan-agglutinin identified in plasma. Invalid ABO blood grouping occurred in 4 of 12 (33%) non-group O patients due to anomalous reactivity in the reverse ABO-type results., Conclusions: Treatment with Hu5F9-G4 in patients with AML resulted in an Hb decline and increased transfusion requirements. Problems with ABO blood typing and compatibility testing were widely observed and should be expected by centers treating recipients of Hu5F9-G4., (© 2019 AABB.)

Anemia of inflammation (AI), also known as anemia of chronic disease (ACD), is regarded as the most frequent anemia in hospitalized and chronically ill patients. It is prevalent in patients with diseases that cause prolonged immune activation, including infection, autoimmune diseases, and cancer. More recently, the list has grown to include chronic kidney disease, congestive heart failure, chronic pulmonary diseases, and obesity. Inflammation-inducible cytokines and the master regulator of iron homeostasis, hepcidin, block intestinal iron absorption and cause iron retention in reticuloendothelial cells, resulting in iron-restricted erythropoiesis. In addition, shortened erythrocyte half-life, suppressed erythropoietin response to anemia, and inhibition of erythroid cell differentiation by inflammatory mediators further contribute to AI in a disease-specific pattern. Although the diagnosis of AI is a diagnosis of exclusion and is supported by characteristic alterations in iron homeostasis, hypoferremia, and hyperferritinemia, the diagnosis of AI patients with coexisting iron deficiency is more difficult. In addition to treatment of the disease underlying AI, the combination of iron therapy and erythropoiesis-stimulating agents can improve anemia in many patients. In the future, emerging therapeutics that antagonize hepcidin function and redistribute endogenous iron for erythropoiesis may offer additional options. However, based on experience with anemia treatment in chronic kidney disease, critical illness, and cancer, finding the appropriate indications for the specific treatment of AI will require improved understanding and a balanced consideration of the contribution of anemia to each patient's morbidity and the impact of anemia treatment on the patient's prognosis in a variety of disease settings., (© 2019 by The American Society of Hematology.)

Declining a treatment modality should not be considered the same as refusal of medical care as illustrated by the management of Jehovah's Witness patients who do not accept transfusions. Over the years, a comprehensive set of strategies have been developed to meet the specific needs of these patients and these strategies are collectively called "Bloodless Medicine and Surgery" (BMS). The focus in BMS is to optimize the patients' hematopoietic capacity to increase hemoglobin (Hgb) level, minimize blood loss, improve hemostasis, and provide supportive strategies to minimize oxygen consumption and maximize oxygen utilization. We present 3 case reports that illustrate some of the challenges faced and measures available to effectively treat these patients. Under BMS programs, patients with extremely low hemoglobin levels, not conducive to survival under ordinary conditions, have survived and recovered without receiving allogeneic transfusions. Additionally, the valuable experience gained from caring for these patients has paved the way to develop the concept of Patient Blood Management as a standard care to benefit all patients, and not only those for whom blood is not an option., (© 2018 Wiley Periodicals, Inc.)

Background: The incidence of placenta accreta (PA) has increased from 0.8 to 3.0 in 1000 pregnancies, driven by increased rates of cesarean deliveries (32.2% in 2014) of births in the United States. The average blood loss for a delivery complicated by PA ranges from 2000 to 5000 mL, frequently requiring substantial transfusion medicine support. We report our own institutional multidisciplinary approach for managing such patients, along with transfusion medicine outcomes, in this setting over a 5-year period., Methods: We reviewed records for patients referred to our program in placental disorders from July 1, 2009, to July 1, 2014. A placental disorders preoperative checklist was implemented to ensure optimal management of patients with peripartum hemorrhage., Results: Of 136 patients whose placentas were reviewed postpartum, 21 had PA, 39 had microscopic PA, 17 had increta, 17 had percreta, and 42 had no accreta (of which 11 had placenta previa). For each subtype, the percentage of patients receiving blood products were 71% (PA), 28% (microscopic PA), 82% (increta), 82% (percreta), and 19% (no accreta). Among patients with PA or variants, 89% of patients with PA or variants underwent postpartum hysterectomy, compared to only 5% of patients with no or microscopic PA., Conclusions: Based on our experience and on the findings of our retrospective analysis, patients presenting with either antepartum radiological evidence or clinical suspicion of morbidly adherent placenta will benefit from a standardized protocol for clinical management, including transfusion medicine support. We found that massive hemorrhage is predictable when abnormal placentation is identified predelivery and that blood product support is substantial regardless of the degree of placental invasiveness. The protocol at our institution provides immediate access to sufficient volumes and types of blood products at delivery for patients at highest risk for life-threatening obstetric hemorrhage. Therefore, for patients with a diagnosis of morbidly adherent placenta scheduled for planned cesarean delivery with possible hysterectomy, a programmatic checklist that mobilizes a multidisciplinary team, including proactive transfusion medicine support, represents best practices.

Objectives: To curtail inappropriate plasma transfusions, we instituted clinical decision support as an alert upon order entry if the patient's recent international normalized ratio (INR) was 1.7 or less., Methods: The alert was suppressed for massive transfusion and within operative or apheresis settings. The plasma order was automatically removed upon alert acceptance while clinical exception reasons allowed for continued transfusion. Alert impact was studied comparing a 7-month control period with a 4-month intervention period., Results: Monthly plasma utilization decreased 17.4%, from a mean ± SD of 3.40 ± 0.48 to 2.82 ± 0.6 plasma units per hundred patient days (95% confidence interval [CI] of difference, -0.1 to 1.3). Plasma transfused below an INR of 1.7 or less decreased from 47.6% to 41.6% (P = .0002; odds ratio, 0.78; 95% CI, 0.69-0.89). The alert recommendation was accepted 33% of the time while clinical exceptions were chosen in the remaining cases (active bleeding, 31%; other clinical indication, 33%; and apheresis, 2%). Alert acceptance rate varied significantly among different provider specialties., Conclusions: Clinical decision support can help curtail inappropriate plasma use but needs to be part of a comprehensive strategy including audit and feedback for comprehensive, long-term changes., (© American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: More than 30% of the world's population are anemic with serious medical and economic consequences. Red blood cell transfusion is the mainstay to correct anemia, but it is also one of the top five overused procedures and carries its own risk and cost burden. Patient blood management (PBM) is a patient-centered and multidisciplinary approach to manage anemia, minimize iatrogenic blood loss, and harness tolerance to anemia in an effort to improve patient outcome. Despite resolution 63.12 of the World Health Organization in 2010 endorsing PBM and current guidelines which include evidence-based recommendations on the use of diagnostic/therapeutic resources to provide better health care, many hospitals have yet to implement PBM in routine clinical practice., Method and Results: A number of experienced clinicians developed the following "Simplified International Recommendations for Patient Blood Management." We propose a series of simple, cost-effective, best-practice, feasible, and evidence-based measures that will enable any hospital to reduce both anemia prevalence on the day of intervention/surgery and anemia-related unnecessary transfusion in surgical and medical patients, including obstetrics and gynecology.

Transfusion of red blood cells (RBCs) is a balance between providing benefit for patients while avoiding risks of transfusion. Randomized, controlled trials of restrictive RBC transfusion practices have shown equivalent patient outcomes compared with liberal transfusion practices, and meta-analyses have shown improved in-hospital mortality, reduced cardiac events, and reduced bacterial infections. This body of level 1 evidence has led to substantial, improved blood utilization and reduction of inappropriate blood transfusions with implementation of clinical decision support via electronic medical records, along with accompanying educational initiatives., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In developed countries, rates of postpartum hemorrhage (PPH) requiring transfusion have been increasing. As a result, anesthesiologists are being increasingly called upon to assist with the management of patients with severe PPH. First responders, including anesthesiologists, may adopt Patient Blood Management (PBM) recommendations of national societies or other agencies. However, it is unclear whether national and international obstetric societies' PPH guidelines account for contemporary PBM practices. We performed a qualitative review of PBM recommendations published by the following national obstetric societies and international groups: the American College of Obstetricians and Gynecologists; The Royal College of Obstetricians and Gynecologists, United Kingdom; The Royal Australian and New Zealand College of Obstetricians and Gynecologists; The Society of Obstetricians and Gynecologists of Canada; an interdisciplinary group of experts from Austria, Germany, and Switzerland, an international multidisciplinary consensus group, and the French College of Gynaecologists and Obstetricians. We also reviewed a PPH bundle, published by The National Partnership for Maternal Safety. On the basis of our review, we identified important differences in national and international societies' recommendations for transfusion and PBM. In the light of PBM advances in the nonobstetric setting, obstetric societies should determine the applicability of these recommendations in the obstetric setting. Partnerships among medical, obstetric, and anesthetic societies may also help standardize transfusion and PBM guidelines in obstetrics.

Sporadic Zika virus infections had only occurred in Africa and Asia until an outbreak in Micronesia (Oceania) in 2007. In 2013 to 2014, several outer Pacific Islands reported local outbreaks. Soon thereafter, the virus was likely introduced in Brazil from competing athletes from French Polynesia and other countries that participated in a competition there. Transmission is thought to have occurred through mosquito bites and spread to the immunologically naive population. Being also a flavivirus, the Zika virus is transmitted by the Aedes mosquito that is endemic in South and Central America that is also the vector of West Nile virus, dengue, and chikungunya. In less than a year, physicians in Brazil reported a many-fold increase in the number of babies born with microcephaly. Despite initial skepticism regarding the causal association of the Zika virus epidemic and birth defects, extensive basic and clinical research evidence has now confirmed this relationship. In the United States, more than 4000 travel-associated infections have been reported by the middle of 2016 to the Centers for Disease Control and Prevention. Furthermore, many local mosquito-borne infections have occurred in Puerto Rico and Florida. Considering that the virus causes a viremia in which 80% of infected individuals have no symptoms, the potential for transfusion transmission from an asymptomatic blood donor is high if utilizing donor screening alone without testing. Platelet units have been shown to infect 2 patients via transfusion in Brazil. Although there was an investigational nucleic acid test available for testing donors, not all blood centers were initially required to participate. Subsequently, the US Food and Drug Administration issued a guidance in August 2016 that recommended universal nucleic acid testing for the Zika virus on blood donors.In this report, we review the potentially devastating effects of Zika virus infection during pregnancy and its implication in cases of Guillain-Barre syndrome in adults. Furthermore, we urge hospital-based clinicians and transfusion medicine specialists to implement perisurgical patient blood management strategies to avoid blood component transfusions with their potential risks of emerging pathogens, illustrated here by the Zika virus. Ultimately, this current global threat, as described by the World Health Organization, will inevitably be followed by future outbreaks of other bloodborne pathogens; the principles and practices of perioperative patient blood management will reduce the risks from not only known, but also unknown risks of blood transfusion for our patients.

More than 30% of the world's population are anemic with serious economic consequences including reduced work capacity and other obstacles to national welfare and development. Red blood cell transfusion is the mainstay to correct anemia, but it is also 1 of the top 5 overused procedures. Patient blood management (PBM) is a proactive, patient-centered, and multidisciplinary approach to manage anemia, optimize hemostasis, minimize iatrogenic blood loss, and harness tolerance to anemia. Although the World Health Organization has endorsed PBM in 2010, many hospitals still seek guidance with the implementation of PBM in clinical routine. Given the use of proven change management principles, we propose simple, cost-effective measures enabling any hospital to reduce both anemia and red blood cell transfusions in surgical and medical patients. This article provides comprehensive bundles of PBM components encompassing 107 different PBM measures, divided into 6 bundle blocks acting as a working template to develop institutions' individual PBM practices for hospitals beginning a program or trying to improve an already existing program. A stepwise selection of the most feasible measures will facilitate the implementation of PBM. In this manner, PBM represents a new quality and safety standard., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The changing focus of transfusion medicine (TM) toward the hospital rather than the blood center and the involvement of TM specialists in a wide range of patient blood management and other specialist activities in the hospital, rather than just blood bank activities, means that the training of the transfusion specialists of the future should be under constant review., Study Design and Methods: We provide overviews of the current training programs of the Accreditation Council for Graduate Medical Education in the United States and the Joint Royal Colleges of Physicians Training Board in the United Kingdom, along with specific descriptions of our own training programs at Stanford and Oxford., Results: The numbers of TM fellows in training annually in the United States and of those who attempt to attain board certification have increased substantially over the last 20 years, despite the profound reduction in blood utilization since 2009. These trends reflect increasing job and career opportunities in new activities, such as patient blood management at hospital-based transfusion services. This trend has been seen to a lesser extent in the United Kingdom, although the focus of TM is similarly switching to hospital-based transfusion services., Conclusion: Based on current trends, transfusion medicine is a growing and robust specialty in the United States but perhaps less so in the United Kingdom, increasingly with hospital-centered job opportunities for improving blood utilization and clinical outcomes. Establishing pediatric TM training programs and improving research training are further opportunities for training TM specialists., (© 2016 AABB.)

Background: Postpartum hemorrhage (PPH) is a leading cause of obstetric morbidity. There is limited understanding of patients' knowledge about blood loss at delivery, PPH, and PPH-related morbidities, including transfusion and anemia., Methods: We surveyed 100 healthy postpartum patients who underwent vaginal or cesarean delivery about blood loss, and whether they received information about transfusion and peripartum hemoglobin (Hb) testing. Responses were compared between women undergoing vaginal delivery vs. cesarean delivery; P < 0.05 considered as statistically significant., Results: In our cohort, 49 women underwent vaginal delivery and 51 women underwent cesarean delivery. Only 29 (29%) of women provided blood loss estimates for their delivery. Women who underwent cesarean delivery were more likely to receive clear information about transfusion therapy than those undergoing vaginal delivery (43.1% vs. 20.4% respectively; P = 0.04). Women who underwent vaginal delivery were more likely to receive results of postpartum Hb tests compared to those undergoing cesarean delivery (49% vs. 29.4%; P = 0.02)., Conclusion: Our findings suggest that women are poorly informed about the magnitude of blood loss at delivery. Hematologic information given to patients varies according to mode of delivery. Further research is needed to better understand the clinical implications of patients' knowledge gaps about PPH, transfusion and postpartum anemia., Competing Interests: The authors declare there are no competing interests.

Background: Hypotensive transfusion reactions (HyTRs) may be underreported and have been associated with patients taking angiotensin-converting enzyme inhibitors (ACEIs) receiving poststorage leukoreduced blood products through negatively charged filters. Although bedside leukoreduction is no longer commonplace, HyTRs still occur and are insufficiently characterized in the prestorage leukoreduction era. We describe recently reported cases at our institution., Methods: We reviewed transfusion reaction records at Stanford Healthcare from January 2014 to April 2015. HyTRs were defined by National Health Safety Network Hemovigilance Module classification., Results: Eleven HyTRs occurred in 10 patients. All were adults (mean age 71.7 years; range 45-92 years), 7 were male, and all underwent major surgery 0 to 2 days before the reaction. Nine patients underwent cardiac or vascular surgery, and all 10 were taking ACEIs with the last dose taken within 48 hours of the transfusion reaction in 9 patients. Nine patients were on extracorporeal circuits within 24 hours before the reaction (median duration 180 minutes; range 87-474 minutes). In 5 reactions, the implicated unit was restarted with resultant recurrent hypotension. Implicated units included 9 packed red blood cells, 1 apheresis platelet, and 1 plasma frozen within 24 hours., Conclusions: Contrary to what has been previously reported in the era of prestorage leukoreduction, HyTRs at our institution showed consistent patterns in patients at risk. Patients scheduled to undergo major surgery with cardiopulmonary bypass may benefit from earlier preoperative cessation of ACEIs or temporarily switching to an alternative drug class.

Objectives: The rate of plasma product wastage for the United States in 2011 was approximately 1.8%. The plasma wastage rate at our institution was higher, mainly due to products returned out of temperature range from procedural areas. A process review and intervention to reduce plasma wastage was undertaken, which included modifications to our transport cooler., Methods: A new cooler system was designed, and this device was implemented alongside an updated protocol for delivering plasma while also enhancing the previous RBC cooler validation time. We audited plasma and RBC product wastage prior to these interventions, from January 2013 to February 2014, vs after the intervention from April 2014 to March 2015., Results: After the intervention, the monthly plasma wastage rate declined 60% (12.6 units/100 units transfused preintervention vs 5.0 units/100 units transfused postintervention; P < .0001). The monthly RBC wastage rate also decreased 28% (3.2 units/100 units transfused preintervention vs 2.3 units/100 units transfused postintervention; P < .01)., Conclusions: Our intervention resulted in significantly decreased plasma and RBC wastage and is broadly applicable, since out-of-temperature product wastage in procedural areas is likely a significant problem at many institutions., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recombinant activated factor VIIa (rFVIIa) is a prohemostatic agent initially approved for use in hemophilia patients with inhibitors and recently for Glanzmann thrombasthenia. Despite its approval indications, rFVIIa has also been used for a diverse range of off-label indications to treat bleeding related to traumatic injury, major hemorrhage following surgery, intracranial hemorrhage, and for uncontrolled bleeding as a prothrombotic hemostatic agent. Despite its off-label use, the benefit of rFVIIa in most nonhemophilia settings remains uncertain as the majority of clinical trials have not consistently demonstrated beneficial effects as determined by reduced bleeding, decreased blood product utilization, or have not demonstrated a mortality benefit. As with any prohemostatic agent, the risk of thromboembolic events is increased when rFVIIa is used off-label. Pooled data from randomized nonhemophilia studies report an increased risk in the elderly for arterial thromboses, although most individual trials have been underpowered to determine adverse thrombotic events. The causes of thrombotic adverse events associated with off-label use of rFVIIa may be due to an increased risk of adverse events due to critical illness or due to higher doses of rFVIIa used in off-label trials. Without clearly supportive data, physicians should consider risk versus benefit and exercise restraint using rFVIIa in off-label settings. Further, evidence-based guidelines should be developed by professional organizations, and additional randomized controlled clinical trials are needed to further assess the efficacy and safety of off-label rFVIIa use., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Plasma volume reduction (PVR) may reduce the risk of hemolysis associated with transfusion of plateletpheresis blood products (PLTs) containing ABO-incompatible plasma. But PVR may delay PLT issue. In collaboration with our blood donor center we evaluated an automated screen of PLT for high-titer ABO antibody and to apply PVR to high-titer PLTs., Study Design and Methods: At the donor center, plasma from PLT donors was tested using an automated microplate system (PK7300, Beckman). PK settings were set for a detection cutoff equivalent to 1 in 256 using a manual tube method. The donors associated with high-titer PLTs were characterized by sex and age. In the transfusion service, the number of PVR procedures was evaluated before and after implementation of the high-titer screen., Results: During validation, 157 of 1008 PLT units (15%) were positive by the automated method versus 121 (12%) by manual method. After implementation, 2112 of 15,240 PLT units were high-titer, with higher frequency in donations from females versus males (18% vs. 12%, p < 0.0001). The PLT PVR rate was reduced by 50%., Conclusion: Implementation of an automated method to screen PLTs for high-titer ABO antibody at the donor center improves the inventory management of PLTs containing ABO-incompatible plasma at the hospital transfusion service., (© 2015 AABB.)

Blood transfusion has been identified as one of the most frequently performed therapeutic procedures, with a significant percentage of transfusions identified to be inappropriate. Recent key clinical trials in adults have provided Level 1 evidence to support restrictive red blood cell (RBC) transfusion practices. However, some advocates have attempted to identify a "correct" Hb threshold for RBC transfusion; whereas others assert that management of anemia, including transfusion decisions, must take into account clinical patient variables, rather than simply one diagnostic laboratory test. The heterogeneity of guidelines for blood transfusion by a number of medical societies reflects this controversy. Clinical decision support (CDS) uses a Hb threshold number in a smart Best Practices Alert (BPA) upon physician order, to trigger a concurrent utilization self-review for whether blood transfusion therapy is appropriate. This review summarizes Level 1 evidence in seven key clinical trials in adults that support restrictive transfusion practices, along strategies made possible by CDS that have demonstrated value in improving blood utilization by promoting restrictive transfusion practices., (© 2015 Wiley Periodicals, Inc.)

Anemia is present in over two-thirds of patients with malignant hematological disorders. The etiology of anemia predominates from ineffective erythropoiesis from marrow infiltration, cytokine related suppression, erythropoietin suppression, and vitamin deficiency; ineffective erythropoiesis is further exacerbated by accelerated clearance due to antibody mediated hemolysis and thrombotic microangiopathy. As the anemia is chronic in nature, symptoms are generally well tolerated and often non-specific. Transfusion of red blood cells (RBCs) is a balance between providing benefit for patients while avoiding risks of transfusion. Conservative/restrictive RBC transfusion practices have shown equivalent patient outcomes compared to liberal transfusion practices, and meta-analysis has shown improved in-hospital mortality, reduced cardiac events, re-bleeding, and bacterial infections. The implications for a lower threshold for transfusion in patients with malignancies are therefore increasingly being scrutinized. Alternative management strategies for anemia with IV iron and erythropoietin stimulating agents (ESAs) should be considered in the appropriate settings., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Patient blood management is an increasingly used term to describe an evidence-based, multidisciplinary approach to optimising the care of patients who might need transfusion. It encompasses measures to avoid transfusion such as anaemia management without transfusion, cell salvage and the use of anti-fibrinolytic drugs to reduce bleeding as well as restrictive transfusion. It ensures that patients receive the optimal treatment, and that avoidable, inappropriate use of blood and blood components is reduced. This paper provides an overview of the scientific basis for patient blood management with a focus on the increasing evidence for restrictive rather than liberal transfusion practice and the use of electronic blood ordering and decision support to facilitate its implementation., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Purpose of Review: Major obstetric hemorrhage is a leading cause of maternal morbidity and mortality. We will review transfusion strategies and the value of monitoring the maternal coagulation profile during severe obstetric hemorrhage., Recent Findings: Epidemiologic studies indicate that rates of severe postpartum hemorrhage (PPH) in well resourced countries are increasing. Despite these increases, rates of transfusion in obstetrics are low (0.9-2.3%), and investigators have questioned whether a predelivery 'type and screen' is cost-effective for all obstetric patients. Instead, blood ordering protocols specific to obstetric patients can reduce unnecessary antibody testing. When severe PPH occurs, a massive transfusion protocol has attracted interest as a key therapeutic resource by ensuring sustained availability of blood products to the labor and delivery unit. During early postpartum bleeding, recent studies have shown that hypofibrinogenemia is an important predictor for the later development of severe PPH. Point-of-care technologies, such as thromboelastography and rotational thromboelastometry, can identify decreased fibrin clot quality during PPH, which correlate with low fibrinogen levels., Summary: A massive transfusion protocol provides a key resource in the management of severe PPH. However, future studies are needed to assess whether formula-driven vs. goal-directed transfusion therapy improves maternal outcomes in women with severe PPH.

Introduction: Iron deficiency anemia (IDA) remains a widely underdiagnosed and unappreciated women's health issue, affecting women of all ages. Despite the fact that IDA is easily diagnosed and treated, it continues to be a major public health issue. The World Health Organization estimates that 30% of nonpregnant and more than 42% of pregnant women have anemia., Methods: A multidisciplinary Group for the Research and Education on Anemia Therapy in Women (GREAT Women II) was formed, sponsored by the Society for the Advancement of Blood Management. The goal was to focus attention on the impact of IDA on women at various stages of life and evaluate and use published literature to provide a simple, evidence-based approach to diagnose and treat IDA., Results: The group developed specific recommendations for evaluating and treating IDA in women. Initial diagnosis is defined as hemoglobin less than 12 g/dL in nonpregnant women. A trial of iron therapy (4 weeks) can be considered a first-line diagnostic tool. Alternatively, a low or normal mean corpuscular volume (<100 fL), low serum ferritin (<30 μg/L), and/or low transferrin saturation (transferrin saturation <20%) is sufficient to confirm IDA. If the patient does not fit the diagnosis of IDA or fails to respond to a trial of oral iron, or mean corpuscular volume is elevated, further diagnostic evaluation is needed, including iron studies, B12, folate levels, and renal function tests. If results are not definitive, and IDA persists, a hematology referral is recommended., Conclusion: Clinicians should routinely identify and treat IDA, thereby decreasing its negative impact on health and quality of life of women.

Context: Hemoglobinuria was observed after packed red blood cell transfusion in a series of patients at our pediatric treatment center. Laboratory testing was suggestive of intravascular hemolysis with no support for an immunohematologic process., Objective: We investigated these adverse events to define a quality improvement plan and to prevent future hemolytic adverse events. Multiple factors were investigated, and the only change identified was the implementation of a new infusion pump (Pump A) that replaced a previous model (Pump B)., Design: In vitro pump analyses, a retrospective review of urinalyses, and prospective urinalysis and nursing surveillances were also performed., Results: In in vitro analysis of the pumps, irradiated units with higher hematocrit at a low flow rate through Pump A had a greater than thirty-fold increase in free hemoglobin from baseline compared to minimal free hemoglobin changes seen with Pump B. Irradiated units with a lower hematocrit had a minimal change in free hemoglobin from baseline with both Pumps A and B at either low or high flow rate. Subsequently, only units with lower hematocrits were issued for transfusion of pediatric patients, and Pump A was replaced by Pump B in the outpatient unit. Retrospective and prospective surveillances found no additional unexplained cases of gross hemoglobinuria associated with transfusion., Conclusion: The investigation determined that infusion of higher hematocrit units using a specific commercial pump was associated with mechanical hemolysis. The change to units with lower hematocrit through an alternative pump has been an effective corrective action to date., (© 2015 by the Association of Clinical Scientists, Inc.)

Fibrinogen is a critical protein for hemostasis and clot formation. However, transfusion guidelines have variable recommendations for maintaining fibrinogen levels in bleeding patients. An increasing number of studies support the practice of fibrinogen replacement therapy for acquired coagulopathies, and additional studies are underway. Fibrinogen therapy can be administered with cryoprecipitate or fibrinogen concentrates, and clinical practice varies according to their availability and licensing status. Fibrinogen concentrate therapy has been studied in animal models and clinical trials and supports the critical role of fibrinogen repletion in bleeding patients. Point-of-care testing will have an important role in guiding fibrinogen replacement for hemostatic therapy in clinical settings such as cardiovascular surgery, postpartum hemorrhage, and trauma. Fibrinogen therapy is an important component of a multimodal strategy for the treatment of coagulopathic bleeding., (© 2015 by The American Society of Hematology.)

Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA), we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV) iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7), we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1-5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p < 0.001) lower (5.6%) in the 1500 mg group, compared to the 1000 mg group (11.1%). Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.