Mitigation strategies for anti-D alloimmunization by platelet transfusion in haematopoietic stem cell transplant patients: a survey of NCCN® centres.

BACKGROUND AND OBJECTIVES: D-negative patients are at risk of developing an alloantibody to D (anti-D) if exposed to D during transfusion. The presence of anti-D can lead to haemolytic transfusion reactions and haemolytic disease of the newborn. Anti-D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti-D alloimmunization with special attention in patients considered for HSCT. METHODS AND MATERIALS: To understand transfusion practices regarding D-positive platelets in D-negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network® (NCCN® ). RESULTS: Nineteen centres responded (68%). Most centres (79%) avoid transfusing D-positive platelets to RhD-negative patients when possible. Four centres (21%) avoid D-positive platelets only in D-negative women of childbearing age. If a D-negative patient receives a D-positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D-negative patients who are HSCT candidates including adult men and women of no childbearing age. CONCLUSION: There is wide variation in platelet transfusion practices for supporting D-negative patients. The majority of centres do not have D-positive platelet transfusion policies focused on preventing anti-D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti-D alloimmunization in HSCT patients.

Hematologic improvement with iron chelation therapy in myelodysplastic syndromes: Clinical data, potential mechanisms, and outstanding questions.

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenias and progression to acute myeloid leukemia (AML). Although several treatments for MDS are available, the mainstay of therapy for most patients remains supportive care. This includes red blood cell (RBC) transfusion to correct anemia, which leads to iron overload. RBC transfusion dependence and iron overload portend inferior overall survival. Some studies indicate that iron chelation therapy (ICT) may have beneficial effects on clinical endpoints in MDS; however, these data are from non-randomized trials and the validity of the results is vigorously debated. A consistent observation in clinical studies of ICT in MDS has been hematologic improvement (HI) in some patients, including a reduction in RBC transfusion requirements and even transfusion independence. Here, we review data on HI with ICT in lower risk MDS, preclinical data examining mechanisms by which HI may occur, and identify areas for future investigation.

Myocardial Iron Overload in Sickle Cell Disease: A Rare But Potentially Fatal Complication of Transfusion.

Sickle cell disease (SCD) is a frequent indication for chronic transfusion, which can cause iron overload. Excess iron often affects the liver, but not the heart in SCD. Magnetic resonance (MR) is recommended to detect myocardial iron overload (MIO) but its elevated cost requires optimized indication. We aimed to compile all published data on MIO in SCD upon the description of a fatal case of severe MIO in our institution, and to determine associated risk factors. We performed a systematic review using the PRISMA guidelines in two databases (PubMed and Web of Science). Inclusion criteria were publication in English, patients diagnosed with SCD, and reporting ferritin and MIO by MR. Twenty publications reported on 865 SCD adult and pediatric patients, with at least 10 other cases of MIO. The prevalence of MIO in chronically transfused SCD patients can be estimated to be 3% or less, and is associated with high transfusion burden, top-up transfusions, and low adherence to iron chelation. Cardiac siderosis in SCD is rarely reported, and increased awareness with better use of the available screening tools are necessary. Prospective studies should define the recommended chelation regimens depending on the severity of MIO.

Is there a risk of transfusion-transmissible infections after percutaneous needle treatments in blood donors? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The donor medical questionnaire identifies a blood donor's history of known blood safety risks. Current Australian, Canadian, European and USA legislation temporarily defers blood donors who received different percutaneous needle treatments (i.e. tattooing, acupuncture and piercing) from blood donation. This systematic review aimed to scientifically underpin these deferrals by identifying the best available evidence on the association between percutaneous needle treatments and the risk of transfusion-transmissible infections (TTIs). MATERIALS AND METHODS: Studies from three databases investigating the link between percutaneous needle treatments and TTIs (HBV, HCV and HIV infection) in blood donors were retained and assessed on eligibility by two reviewers independently. The association between percutaneous needle treatments and TTIs was expressed by conducting meta-analyses and calculating pooled effect measures (odds ratios (ORs) and 95% CIs). The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS: We identified 1242 references and finally included 21 observational studies. Twenty studies assessed the link between percutaneous needle treatments and HCV infection and found that blood donors receiving these treatments had an increased risk of HCV infection (tattooing: pooled OR 5·28, 95% CI [4·33, 6·44], P < 0·00001 (low-quality evidence); acupuncture: pooled OR 1·56, 95% CI [1·17, 2·08], P = 0·03 (very low-quality evidence); and piercing: pooled OR 3·25, 95% CI [1·68, 6·30], P = 0·0005 (low-quality evidence)). CONCLUSION: Percutaneous needle treatments may be associated with an increased HCV infection risk. Further high-quality studies are required to formulate stronger evidence-based recommendations on percutaneous needle treatments as a blood donor deferral criterion.

Screening the Blood Supply for Zika Virus in the 50 U.S. States and Puerto Rico: A Cost-Effectiveness Analysis.

Background: In 2016, universal individual donation nucleic acid testing (ID-NAT) of donated blood for Zika virus began in U.S. states and territories. Objective: To assess the cost-effectiveness of universal ID-NAT in the first year of screening compared with alternatives for the 50 states and separately for Puerto Rico. Design: Microsimulation that captured Zika-related harms to transfusion recipients, sexual partners, and their infants. Data Sources: National testing results compiled by AABB and costs, utilities, and outcome probabilities estimated from the literature. Target Population: Transfusion recipients. Time Horizon: Lifetime. Perspective: Societal. Intervention: Universal ID-NAT, universal mini-pool NAT (MP-NAT), and ID-NAT exclusively for components transfused to women of childbearing age. Seasonally targeted strategies in Puerto Rico and geographically targeted strategies in the 50 states were also considered. Outcome Measures: Costs, quality-adjusted life-years (QALYs), and outcomes. Results of Base-Case Analysis: In Puerto Rico, MP-NAT exclusively during high mosquito season was cost-effective at $81 123 per QALY (95% CI, -$49 138 to $978 242 per QALY). No screening policy was cost-effective in the 50 states. Universal ID-NAT cost $341 million per QALY (CI, $125 million to $2.90 billion per QALY) compared with no screening in the 50 states. Results of Sensitivity Analysis: In Puerto Rico, MP-NAT only during the season of high mosquito activity was most cost-effective in 64% of probabilistic sensitivity analysis iterations. In the 50 states, no intervention was cost-effective in 99.99% of iterations. Cost-effectiveness was highly dependent on the rate of assumed infectious donations. Limitation: Data were limited on the component-specific transmissibility of Zika and long-term sequelae of infection. Conclusion: Screening was cost-effective only in the high mosquito season in Puerto Rico, and no evaluated screening policy was cost-effective in the 50 states. During periods with lower rates of Zika-infectious donations, the cost-effectiveness of screening will be even less favorable. Primary Funding Source: None.

Retrospective analysis of HDFN due to ABO incompatibility in a single institution over 6 years.

OBJECTIVES: To study the rate of ABO haemolytic anaemia of fetus and newborn (HDFN) in one institution over 6 years. BACKGROUND: ABO major incompatibility between mothers and their newborns occurs in about 10% of births. So, mothers with an O blood group may form IgG-class antibodies against A and B antigens, which could pass across the placenta and lead to a variable degree of HDFN in the newborn. METHODS: At our institution, we have reviewed data regarding ABO-based HDFN in the last 6 years. RESULTS: We found that, in 28 089 deliveries, an ABO major incompatibility between mothers and newborns occurs in 11% of cases, with 72% of O/A and 28% of O/B incompatibility. In turn, 23% of these newborns had an eluate-confirmed positive direct antiglobulin test [DAT; 74% (511) were due to anti-A and 26% (179) to anti-B], with 1·0% requiring invasive treatments (exchange transfusion or intravenous immunoglobulin). Overall, 2·5% of the total newborns had a positive DAT for an anti-A or anti-B antibody, and 0·11% required invasive treatment in addition to phototherapy for their HDFN. CONCLUSIONS: Serological ABO HDFN is a relatively frequent event when an O-A/O-B incompatibility between mothers and their newborn occurs and, in most cases, translates into a self-limiting disease, with a small number of newborns requiring invasive treatments. The DAT test, although not predictive of disease severity, appears to be a useful tool to monitor babies born from O-A/O-B-incompatible pregnancies and to identify those who may require treatment.

Blood Products in the Management of Abnormal Placentation.

A critical tool in the successful management of patients with abnormal placentation is an established massive transfusion protocol designed to rapidly deliver blood products in obstetrical and surgical hemorrhage. Spurred by trauma research and an understanding of consumptive coagulopathy, the past 2 decades have seen a shift in volume resuscitation from an empiric, crystalloid-based method to balanced, targeted transfusion therapy. The present article reviews patient blood management in abnormal placentation, beginning with optimizing the patient's status in the antenatal period to the laboratory assessment and transfusion strategy for blood products at the time of hemorrhage.

How to mitigate the risk of inducing transfusion-associated adverse reactions.

Transfusion has become extremely safe but can still be associated with adverse reactions. Some adverse reactions can be mitigated by applying measures to donor selection, the process of separating blood components as well as hospital-based procedures consisting in matching the donor and the recipient; special attention is given to optimizing the best fit between the component and the beneficiary, which is not only an immuno-hematological challenge (fresh versus old blood, testing for certain viruses such as CMV, parvovirus B19, etc.). Considerable progress has also been achieved to strengthen the overall quality and safety of the whole transfusion chain. Guidelines and recommendations have resulted in substantial progress, and the recent revisiting of patients as part of a more holistic approach has enabled blood management programs to be created. Such programs, when wisely applied in a context of optimal blood use, reinforce patient safety; they enhance hospital recognition of transfusion and hemovigilance specialists as useful players acting in the interests of patients in full compliance with hospital budgets. This review considers the step-by-step processes that reinforce transfusion safety and identifies hurdles that cannot yet be properly addressed; it proposes steps for further progress, in light of personalized medicine.

Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform.

INTRODUCTION: Despite the availability of effective iron chelators, transfusion-related morbidity is still a challenge in chronically transfused patients with myelodysplastic syndromes (MDS). In these patients, transfusion-induced iron overload may lead to organ dysfunction or even organ failure. In addition, iron overload is associated with reduced overall survival in MDS. Areas covered: During the past 10 years, various guidelines for the management of MDS patients with iron overload have been proposed. In the present article, we provide our updated recommendations for the diagnosis, prevention and therapy of iron overload in MDS. In addition, we propose refined treatment response criteria. As in 2006 and 2007, recommendations were discussed and formulated by participants of our Austrian MDS platform in a series of meetings in 2016 and 2017. Expert commentary: Our updated recommendations should support early recognition of iron overload, optimal patient management and the measurement of clinical responses to chelation treatment in daily practice.

Safety of leucodepleted salvaged blood in oncological surgery: an in vitro model.

Intra-operative blood cell salvage (IOCS) is mainly avoided in onco surgery due to the suspicion that it could increase metastasis' risk. We simulated IOCS followed by leucodepletion: HCT116 (human colorectal cancer) cells were inoculated into packed red blood cells units, and their distribution was evaluated, step-by-step, by flow cytometry and immunohistochemistry. Most of HCT116 cells were lost during washing, and almost completely removed after filtration. IOCS plus leucodepletion could be of great advantage for oncological patients, where allogenic blood transfusion could influence tumour progression.

Perioperative Blood Management in Pediatric Spine Surgery.

Blood management strategies are integral to successful outcomes in many types of orthopaedic surgery. These strategies minimize blood loss and transfusion requirements, ultimately decreasing complications, improving outcomes, and potentially eliminating risks associated with allogeneic transfusion. Practices to achieve these goals include preoperative evaluation and optimization of hemoglobin, the use of pharmacologic agents or anesthetic methods, intraoperative techniques to improve hemostasis and cell salvage, and the use of predonated autologous blood. Guidelines can also help manage allogeneic transfusions in the perioperative period. Although the literature on blood management has focused primarily on arthroplasty and adult spine surgery, pediatric spinal fusion for scoliosis involves a large group of patients with a specific set of risk factors for transfusion and distinct perioperative considerations. A thorough understanding of blood management techniques will improve surgical planning, limit transfusion-associated risks, maintain hemostasis, and optimize outcomes in this pediatric population.

Perioperative bleeding management in pediatric patients.

PURPOSE OF REVIEW: Managing the bleeding pediatric patient perioperatively can be extremely challenging. The primary goals include avoiding hypotension, maintaining adequate tissue perfusion and oxygenation, and maintaining hemostasis. Traditional bleeding management has consisted of transfusion of autologous blood products, however, there is strong evidence that transfusion-related side-effects are associated with increased morbidity and mortality in children. Especially concerning is the increased reported incidence of noninfectious adverse events such as transfusion-related acute lung injury, transfusion-related circulatory overload and transfusion-related immunomodulation. The current approach in perioperative bleeding management of the pediatric patient should focus on the diagnosis and treatment of anemia and coagulopathy with the transfusion of blood products only when clinically indicated and guided by goal-directed strategies. RECENT FINDINGS: Current guidelines recommend that a comprehensive multimodal patient blood management strategy is critical in optimizing patient care, avoiding unnecessary transfusion of blood and blood product and limiting transfusion-related side-effects. SUMMARY: This article will highlight current guidelines in perioperative bleeding management for our most vulnerable pediatric patients with emphasis on individualized targeted intervention using point-of-care testing and specific coagulation products.