Transfusion Medicine Reviews最新文献

The current recommended testing algorithm for assessing the alloimmunized pregnancy utilized by many obstetricians in the United States (US) fails to consider the most recent evidence, placing fetuses, and mothers at unnecessary risk of poor outcome or death. This narrative review of the current landscape of fetal red blood cell (RBC) antigen testing evaluates the history of hemolytic disease of the fetus and newborn (HDFN) and how its discovery has continued to influence practices in the US today. We compare current US-based HDFN practice guidelines with those in Europe. We also provide transfusion medicine and hematology perspectives and recommendations addressing the limitations of US practice, particularly regarding paternal RBC antigen testing, and discuss the most valuable alternatives based on decades of data and evidence-based recommendations from Europe.

K-associated anemic disease of the fetus and newborn (K-ADFN) is a rare but life-threatening disease in which maternal alloantibodies cross the placenta and can mediate an immune attack on fetal red blood cells expressing the K antigen. A considerably more common disease, D-associated hemolytic disease of the fetus and newborn (D-HDFN), can be prophylactically treated using polyclonal α-D antibody preparations. Currently, no such prophylactic treatment exists for K-associated fetal anemia, and disease is usually treated with intrauterine blood transfusions. Here we review current understanding of the biology of K-associated fetal anemia, how the maternal immune system is sensitized to fetal red blood cells, and what is understood about potential mechanisms of prophylactic HDFN interventions. Given the apparent challenges associated with preventing alloimmunization, we highlight novel strategies for treating sensitized mothers to prevent fetal anemia that may hold promise not only for K-mediated disease, but also for other pathogenic alloantibody responses.

Anti-D alloimmunization in the first trimester of pregnancy has long been the subject of prevention with anti-D immunoglobulins during events at risk of fetomaternal hemorrhage. Although the efficacy of preventing anti-D alloimmunization by an injection of immunoglobulin at 28 weeks of gestation (WG) is obvious, the literature provides little evidence of the effectiveness before 12⁺⁶ WG and several countries have modified their recommendations. In the presumed absence of a difference in alloimmunization risk between early and late prevention, our objective was to evaluate and compare the cost of treatment for 3 alloimmunization prevention strategies in France, the United Kingdom, and the Netherlands. This was a single-center retrospective study. Our target population included all women who received anti-D immunoglobulins (Rhophylac) in the first trimester of pregnancy before 12⁺⁶ WG at Nantes University Hospital in 2018 (N = 356). Within the target population, 2 other populations were constituted based on British (N = 145) and Dutch (N = 142) clinical practice guidelines (CPG). These 3 populations were analyzed for the comparative cost of treatment for prevention from a health system perspective. The average cost of Rhophylac alloimmunization prevention for 1 episode was €117.8 from a health system perspective. The total cost attributed to prevention in 2018 at Nantes University Hospital (N = 356) was €41,931.4 according to this perspective. If the UK CPG or Dutch CPG had been applied to the Nantes target population, a saving of around 60% would have been achieved. At the national level, the cost according to the health system perspective specifically attributable to induced abortion (N estimated = 26,916) could represent a total cost of €3,170,704. This study highlighted the high cost of the French prevention strategy in the first trimester of pregnancy compared with British or Dutch strategies. The modification of our practices would allow substantial financial savings to the French health system but would also avoid the nonrecommended exposure to a blood product at this term, would allow a faster medical management and a relief of the care system.

Therapeutic plasma exchange (TPE or PLEX) is used in a broad range of autoimmune diseases, with the goal of removing autoantibodies from the circulation. A newer approach for the selective removal of immunoglobulin G (IgG) antibodies is the use of therapeutic molecules targeting the neonatal Fc receptor (FcRn). FcRn regulates IgG recycling, and its inhibition results in a marked decrease in circulating autoantibodies of the IgG subtype. The difference between FcRn inhibition and PLEX is often questioned. With anti-FcRn monoclonal antibodies (mAbs) and fragments only recently entering this space, limited data are available regarding long-term efficacy and safety. However, the biology of FcRn is well understood, and mounting evidence regarding the efficacy, safety, and potential differences among compounds in development is available, allowing us to compare against nonselective plasma protein depletion methods such as PLEX. FcRn inhibitors may have distinct advantages and disadvantages over PLEX in certain scenarios. Use of PLEX is preferred over FcRn inhibition where removal of antibodies other than IgG or when concomitant repletion of missing plasma proteins is needed for therapeutic benefit. Also, FcRn targeting has not yet been studied for use in acute flares or crisis states of IgG-mediated diseases. Compared with PLEX, FcRn inhibition is associated with less invasive access requirements, more specific removal of IgG versus other immunoglobulins without a broad impact on circulating proteins, and any impacts on other therapeutic drug levels are restricted to other mAbs. In addition, the degree of IgG reduction is similar with FcRn inhibitors compared with that afforded by PLEX. Here we describe the scientific literature regarding the use of PLEX and FcRn inhibitors in autoimmune diseases and provide an expert discussion around the potential benefits of these options in varying clinical conditions and scenarios.

Molecular analysis of blood groups is important in transfusion medicine, allowing the prediction of red blood cell (RBC) antigens. Many blood banks use single nucleotide variant (SNV) based methods for blood group analysis. While this is a well-established approach, it is limited to the polymorphisms included in genotyping panels. Thus, variants that alter antigenic expression may be ignored, resulting in incorrect prediction of phenotypes. The popularization of next-generation sequencing (NGS) has led to its application in transfusion medicine, including for RBC antigens determination. The present review/meta-analysis aimed to evaluate the applicability of the NGS for the prediction of RBC antigens. A systematic review was conducted following a comprehensive literature search in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies were selected based on predefined criteria and evaluated using Strengthening the Reporting of Observational studies in Epidemiology guidelines. The characteristics and results of the studies were extracted and meta-analysis was performed to verify the agreement between results from standard molecular methods and NGS. Kell (rs8176058), Duffy (rs2814778, rs12078), or Kidd (rs1085396) alleles were selected as a model for comparisons. Additionally, results are presented for other blood group systems. Of the 864 eligible studies identified, 10 met the inclusion criteria and were selected for meta-analysis. The pooled concordance proportion for NGS compared to other methods ranged from 0.982 to 0.994. The sequencing depth coverage was identified as crucial parameters for the reliability of the results. Some studies reported difficulty in analyzing more complex systems, such as Rh and MNS, requiring the adoption of specific strategies. NGS is a technology capable of predicting blood group phenotypes and has many strengths such as the possibility of simultaneously analyzing hundred individuals and gene regions, and the ability to provide comprehensive genetic analysis, which is useful in the description of new alleles and a better understanding of the genetic basis of blood groups. The implementation of NGS in the routine of blood banks depends on several factors such as cost reduction, the availability of widely validated panels, the establishment of clear quality parameters and access to bioinformatics analysis tools that are easy to access and operate.

Major traumatic hemorrhage is now frequently treated by early hemostatic resuscitation on hospital arrival. Prehospital hemostatic resuscitation could therefore improve outcomes for bleeding trauma patients, but there are logistical challenges. Freeze-dried plasma (FDP) offers indisputable logistical advantages over conventional blood products, such as long shelf life, stability at ambient temperature, and rapid reconstitution without specialized equipment. We sought high level, randomized, controlled evidence of FDP clinical efficacy in trauma. A structured systematic search of MEDLINE/PubMed was carried out and identified 52 relevant English language publications. Three studies involving 607 patients met our criteria: Resuscitation with Blood Products in Patients with Trauma-related Hemorrhagic Shock receiving Prehospital Care (RePHILL, n = 501); Prehospital Lyophilized Plasma Transfusion for Trauma-Induced Coagulopathy in Patients at Risk for Hemorrhagic Shock (PREHO-PLYO, n = 150); and a pilot Australian trial (n = 25). RePHILL found no effect of FDP plus packed red blood cells (PRBC) concentrate transfusion versus saline on mortality. PREHO-PLYO found no effect of FDP versus saline on International Normalized Ratio (INR) at hospital arrival. The pilot trial found that study of PRBC versus PRBC plus FDP was feasible during long air transport times to an Australian trauma centre. Further research is required to determine under what conditions FDP might provide prehospital benefit to trauma patients.

Medication use is extremely common in blood donors. Blood centers use various methods to obtain a history of medication use, all of which have strengths and weaknesses. Some data are available to develop policies for medications that impact product quality, transmissible disease testing, and infectious risks. Many blood centers defer donors for use of a small number of highly teratogenic medications, as a precautionary measure. Others also defer for possible harms related to the pharmacologic effects of medications. However, a single exposure to a blood component containing medication, with immediate dilution in the recipient's blood stream, is a very different situation from ongoing use of medication in a patient, with steady state concentrations achieved over time. It is therefore highly unlikely that these effects are relevant for recipient safety.