Screening of subclinical functional hemoglobin and red blood cell abnormalities among blood donors of Fayoum University Hospital in Egypt: Are RET-He, and IRF useful screening tools?

BACKGROUND: The effectiveness of red cell transfusion in a given blood unit that relied on both quantity and quality of donated cells undoubtedly affects prognostic outcomes. OBJECTIVE: We aimed to determine the frequency of subclinical functional hemoglobin and red cell abnormalities in donated blood of Fayoum University Hospital in Egypt. Additionally, to assess the usefulness of reticulocyte mean hemoglobin content (RET-He) and immature reticulocyte fraction (IRF) as screening measures for such abnormalities. MATERIAL AND METHODS: This cross-sectional study enrolled 200 volunteer blood donors who met the national standard criterion of blood donation. Complete blood count with reticulocyte parameters, serum ferritin, sickling test, G6PD assay, Mentzer index, and naked-eye single tube red cell osmotic fragility test were carried out. RESULTS: Functional red cell abnormalities represented 44 % of this cohort. Out of them, 4.5 % had iron deficiency, 11 % had a positive sickling test, 19 % had G6PD deficiency, and 9.5 % had suspicious thalassemia. The sensitivity and specificity test for RET-He in selective identification of functional hemoglobin abnormalities in donated blood were 83.3 % and 61.2 %, respectively at a cutoff value of 26.9. Though there was no statistically significant effect of RET-He on the selective detection of G6PD deficiency, IRF had a statistically significant high level with a p-value of 0.04. CONCLUSION: Subclinical functional red cell abnormalities seem to be prevalent among blood donors. Reticulocyte/ erythrocyte indices could be useful screening tools for red cell abnormalities. Further studies are required for assessing the impact of transfusing such abnormalities to neonates and other critical recipients.

Transfusion reactions in neonates and pediatrics: How and why are they different?

Neonates and children are physically as well as physiologically different from adults. They are immunologically vulnerable, and the effects of transfusion can be longstanding, including with respect to their development. The transfusion reactions in children differ from those in adults in the type of reactions, incidence, and severity. The incidence is more than that in adults for the common type of reactions noted in children. Transfusion reactions are most commonly associated with platelets, followed by plasma and red blood cell transfusions in children. Febrile, allergic, and hypotensive reactions or volume overload are the common types in children. Standardizing pediatric adverse transfusion reaction definitions and criteria are necessary to improve studies and reports. Several modifications are needed to be adapted for transfusing blood products in neonates and children to evade the reactions as much as possible and make transfusion safer in this vulnerable population. This article provides a brief articulation of the transfusion reactions in neonatal and pediatric populations describing how they are different from adults.

Acute haemolytic transfusion reaction after transfusion of fresh frozen plasma in a neonate-Preventable by using solvent/detergent-treated pooled plasma?

BACKGROUND: Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent-treated plasma has become the standard product in the adult population since several years, but for neonatal use, FFP remains the product of preference. DESCRIPTION: A preterm neonate developed lung bleeding at day 8 postpartum, for which intubation and mechanical ventilation was required and transfusions with packed red blood cells and plasma, in the form of FFP, were given. Five hours after transfusion, a red discoloration of the urine occurred. An acute haemolytic transfusion was suspected, confirmed by laboratory investigations (fast decrease in haemoglobin, increased free haemoglobin, decreased haptoglobin, increased lactate dehydrogenase and a positive direct antiglobulin test [IgG 2+]). Additional research showed that the FFP product contained nonspecific auto-antibodies that reacted with the transfused erythrocytes, most test erythrocytes and the donor's own erythrocytes. CONCLUSION: A neonate experienced an acute haemolytic reaction, most probably caused by administrating a FFP product containing auto-antibodies. If transfused with solvent/detergent-treated plasma, such antibodies would have been diluted or captured. This case adds a new argument to the discussion on expanding the use of solvent/detergent-treated plasma to the paediatric population.

Neonatal and pediatric transfusion practices and policies in India: A survey-based cross-sectional assessment of blood centers.

BACKGROUND: Blood centers play a critical role in supporting neonatal and pediatric transfusions. We aim to study the variation in pediatric/neonatal transfusion policies and practices for blood centers in India. STUDY DESIGN AND METHODS: This is a survey-based (45 question) cross-sectional assessment of blood centers in India supporting pediatric/neonatal transfusions. RESULTS: One hundred three centers responded to the survey (response rate 51.2%; 103/201). As a part of pretransfusion testing, use of "microtainers" was reported by 58.4% (59/101) centers and only 57.4% (58/101) centers provide antibody screening. In case of absence of maternal sample, type O negative blood is most commonly used (48.5%; 49/101), and in case of ABO incompatibility, 68.3% (69/101) use units compatible with both mother and newborn. Leukoreduced RBCs are provided by 89% (90/101) centers and irradiated products are provided by 48.5% (49/101). 82% (83/101) of centers reported not receiving requests for CMV negative units considering the high incidence of CMV-seropositivity in donors. Fresh units are defined as <7 days old by 44.5% (45/101) and <5 days old by 31.6% (32/101) centers. 97% centers reported SAGM suspended RBCs in inventory but only 67.3% (68/101) use them for top-up transfusions to neonates. Overall >80% centers use the buffy-coat method for platelet concentrates preparation. Volume-based (ml/kg) aliquots preparation is done by 88% (89/101), mainly using the sterile connecting device (84.6%; 83/98). CONCLUSION: This survey shows heterogeneity and lack of standardization in practices across blood centers in India and highlights the need for more studies to establish best practices for this vulnerable age group.

Perinatal risk factors associated with severity of haemolytic disease of the foetus and newborn due to Rhc maternal-foetal incompatibility: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Anti-c is the third red blood cell antibody responsible for haemolytic disease of the foetus and newborn (HDFN) requiring intrauterine transfusion. We aimed to identify risk factors associated with HDFN and severe HDFN due to Rhc maternal-foetal incompatibility. MATERIALS AND METHODS: A retrospective cohort study was conducted in Paris and the surrounding area (France), between 2013 and 2015. We included mothers and their children managed by the National Reference Centre in Perinatal Hemobiology for alloimmunization and maternal-foetal incompatibility for the Rhc antigen (N = 121). We conducted bivariate analyses to assess a relationship between perinatal factors (e.g., titre and concentration of anti-c antibodies, direct antiglobulin test) and HDFN, its severity and duration. RESULTS: The incidence of HDFN was 30% (n = 36), including 11% of severe HDFN (n = 13). Seven percent (n = 9) of neonates received at least one transfusion during the first week and 21% (n = 26) after this period until 3 weeks of life. During pregnancy, a concentration ≥7.5 IU/ml and a titre ≥4 and above were associated with HDFN and severe HDFN (p < 0.05). At birth, the high intensity of the quantitative direct antiglobulin test was associated with HDFN and severe HDFN (p < 0.05). A concentration ≥15 IU/ml is the best factor (area under curve [AUC] = 0.78) in predicting HDFN, followed by a titre ≥8 (AUC = 0.76). CONCLUSION: Anti-c alloimmunization causes neonatal anaemia, which is often belated. Paediatricians have to be aware of these risk factors and organize prolonged monitoring of neonates.

Safety of Red Blood Cell Transfusion Using Small Central Lines in Neonates: An in vitro Non-inferiority Study.

Aim: This study aimed to investigate the safety of transfusing red blood cell concentrates (RBCCs) through small [24 gauge (24G)] and extra-small [28 gauge [28G)] peripherally inserted central catheters (PICCs), according to guidelines of transfusion practice in Switzerland. Methods: We performed a non-inferiority in vitro study to assess the safety of transfusing RBCC for 4 h at a 4 ml/h speed through 24G silicone and 28G polyurethane PICC lines, compared with a peripheral 24G short catheter. The primary endpoint was hemolysis percentage. Secondary endpoints were catheter occlusion, inline pressure, and potassium and lactate values. Results: For the primary outcome, hemolysis values were not statistically different among catheter groups (0.06% variation, p = 0.95) or over time (2.75% variation, p = 0.72). The highest hemolysis values in both 24G and 28G PICCs were below the non-inferiority predefined margin. We did not observe catheter occlusion. Inline pressure varied between catheters but followed the same pattern of rapid increase followed by stabilization. Potassium and lactate measurements were not statistically different among tested catheters (0.139% variation, p = 0.98 for potassium and 0.062%, p = 0.96 for lactates). Conclusions: This study shows that RBCC transfusion performed in vitro through 24G silicone and 28G polyurethane PICC lines is feasible without detectable hemolysis or pressure concerns. Also, it adds that, concerning hemolysis, transfusion of RBCC in small and extra-small PICC lines is non-inferior to peripheral short 24G catheters. Clinical prospective assessment in preterm infants is needed to confirm these data further.

Recycling Apparent Waste Into Biologicals: The Case of Umbilical Cord Blood in Italy and Spain.

Most public cord blood banking programs are currently facing financial difficulties due to a progressive decline in the number of cord blood transplants performed worldwide and to a high discard rate of the donated units caused by progressively increasing thresholds of the stem cell dose required to perform safe and effective hemopoietic cord blood transplants. Recycling a proportion of unused cord blood units to prepare novel cord blood components obtained with minimal manipulation (platelets, plasma, red blood cells) and to develop more technologically complex products regulated in the US as Cellular and Gene Therapy Products and in Europe as Advanced Therapy Medicinal Products [e.g. virus-specific T cells (VST), natural killer (NK) cells, induced pluripotent stem cells (iPSCs) is a promising strategy to increase the therapeutic value and reduce the financial deficits of public cord blood banking. Based on encouraging preliminary evidences reported in the literature, additional laboratory studies, large multicenter clinical trials and international regulatory harmonization are necessary to achieve these important goals. This article describes organizational, methodological and regulatory advancements developed in Italy and Spain to promote the clinical use of cord blood platelets, plasma and red blood cells.

Infectious complications in neonatal transfusion: Narrative review and personal contribution.

Neonates and prematures are among the most transfused categories of patients. Adverse reactions due to transfusions, such as transfusion-transmitted infections, can affect the rest of their lives. In this systematic review, we revised the literature concerning transfusion-transmitted infection in neonates. We reported case-reports and case-series previously published and we integrated these data with our experience at local neonatal intensive care unit. Moreover, we illustrated strategies for mitigating transfusion-transmitted infections, including donor selection and testing, pathogen inactivation technologies and combined approaches, as for Cytomegalovirus infection, integrating leukoreduction and identification of seronegative donors.

A new approach to neonatal medical management that could transform the prevention of retinopathy of prematurity: Theoretical considerations.

Retinopathy of prematurity (ROP) is a disease of the immature retina and is the leading global cause of blindness in children. Two postnatal phases of the disease are distinguished, the first phase is thought to be caused by hyperoxia. One of the most relevant ROP risk factor in routine clinical practice is blood transfusion which leads to the introduction into the neonatal circulation of 'non-physiological' adult haemoglobin (HbA) rather than the physiological foetal haemoglobin (HbF). Due to their different affinities for oxygen, HbA will release into retina more oxygen than HbF. It can be expected that this much greater influx of oxygen from HbA may be sensed by the relevant retinal receptors as hyperoxia. Based on the above considerations, I propose that the introduction of non-physiological HbA from adult donors during blood transfusion for anaemia is of key importance in the development and progression of ROP. This hypothesis predicts that there is an HbA limit, beyond which the sequence of events described in the pathogenesis of ROP is triggered. To prevent ROP, I propose launching a new medical field: neonatal transfusion medicine. This system would involve the collection and preparation of umbilical cord blood from the placenta of healthy newborns (containing almost 100% HbF), which would then be administered to premature newborns (who are at risk of ROP) instead of adult blood.

Bleeding emergencies in neonatal and paediatric patients: improving the quality of care using simulation.

OBJECTIVES: Using a multidisciplinary approach and simulation, a massive transfusion process (MTP) was developed to care for patients in need of emergency transfusion. It was then assessed for effectiveness. BACKGROUND: After a series of sentinel emergency bleeding events, a reliable process for hospital staff to deliver appropriate blood products and obtain relevant laboratory tests to guide therapy for patients with emergency bleeding was needed. METHODS: To determine the feasibility of the new MTP, multidisciplinary teams participated in simulation events. Each simulation event helped refine the MTP. A special laboratory testing panel was devised. To judge the effectiveness and timeliness of the MTP, process measures and patient survival was retrospectively evaluated during the time period before and after MTP implementation. RESULTS: A new emergency bleeding panel of laboratory tests significantly decreased the turn-around time for fibrinogen, haematocrit, International normalised ratio (INR) and platelet count. The speed of commencing the first red blood cells transfusion was also improved (2:00 h vs 0:20 min, P = 0·001). Of 78 patients, there was no change in survival before (n = 31, 48·4%) and after (n = 47, 42·6%; P = 0·6478) MTP implementation. However, there was significant improvement in survival associated with MTP events on the weekdays. CONCLUSIONS: A reliable emergency transfusion process consists of an automatic chain of events that keeps decision-making to a minimum and leads to the fast procurement of blood products and salient test results. This work shows that a multidisciplinary iterative process using simulation increases the efficiency of clinical care delivery for bleeding paediatric and neonatal patients.

Dedicated donor unit transfusions reduces donor exposure in pediatric surgery patients.

BACKGROUND: Many strategies have been explored to reduce multiple donor exposures in neonates such as use of restrictive transfusion protocols, limiting iatrogenic blood loss, use of recombinant erythropoietin and single donor programs. METHOD: In our study we assessed the feasibility of dedicating single donor units with reserving all the components from the same donor for the specified neonates/infants undergoing surgery and estimating reduction of donor exposure. Fifty neonates undergoing surgery were included in the prospective study group and the transfusion details were compared with 50 retrospective cases with same inclusion criteria. RESULTS: An intra-operative blood loss of >13 ml/Kg was significantly associated with transfusion (P <0.05) which was most frequently administered in the intra-operative period. Donor exposure rate of overall transfusion was 1.15 in the study group as compared to 4.03 in the retrospective control group. In study group Donor Exposure Rate (DER): Transfusion Rate (TR) ratio was 1:1.5 and Transfusion per Donor Unit (TPDU) of 1.5, means that one donor unit contributed to 1.5 transfusions in each patient and contributed to 50% reduction in donor exposure in each patient as compared to retrospective control group. CONCLUSION: Our study showed that by practicing dedicated donor unit transfusion policy, for neonates undergoing surgery we could significantly reduce the donor exposure.

Utilization Analysis of Neonatal Red Blood Cell Aliquots and Development of Electronic Issuing System / 대한수혈학회지

BACKGROUND: Although transfusion in neonates needs to be strictly regulated due to the vulnerability of neonates, there is lack of systematic studies and the working process is not well-established. This study was aimed to point out the problems of current status and to improve the efficiency of systems used in blood aliquots for neonatal transfusions. METHODS: Total red blood cell (RBC) aliquots were analyzed between May 2009 and January 2016 in the neonate intensive care unit. We investigated the aliquot number, issued day interval from the first issued aliquot among the post-aliquots, patients' blood type, and discarded RBC units among the requested RBC units. RESULTS: Of the 472 RBC aliquots, 95.4% (450/472) were divided into two units. The distribution of patients' blood type was similar to that of the Korean population, in decreasing order: A blood group (34.3%), B group (28.2%), and O group (27.5%). The second, third, and forth units of post-aliquots were taken after an average of 49.9 (0∼617.9) hours. Among the post-aliquots, the number of units discarded without use was 22.5%. CONCLUSION: According to the evaluation of current status for neonatal transfusions, we should use aliquot RBC properly and reduce unnecessary requests for aliquot RBC. In addition, in order to reduce the number of near misses, we propose a new label to be attached on the aliquotted blood bags and suggest a development of electronic blood issuing system.

Neonatal Transfusion Medicine: Five Major Unanswered Research Questions for the Twenty-First Century.

Blood component transfusions are important to the care of preterm neonates; however, their use in clinical practice often is not based on high levels of evidence. Five major questions for neonates are discussed: (1) What is the optimal red blood cell (RBC) transfusion threshold? (2) What is the optimal platelet transfusion threshold? (3) Does the storage age of an RBC unit affect outcomes? (4) Does RBC transfusion contribute to the pathogenesis of necrotizing enterocolitis? and (5) Which new practices should be used to prevent transfusion-transmitted infections? Although definitive answers to these questions do not exist, future research should help answer them.

Eficacia y seguridad de la eritropoyetina en la anemia de la prematuridad / Efficacy and safety of erythropoietin for anemia of prematurity

Introducción: la eritropoyetina alfa recombinante forma parte del tratamiento de la anemia de la prematuridad. En Cuba su uso ha sido limitado y controvertido en cuanto a esquema y dosis empleada. Métodos: ensayo clínico prospectivo, multicéntrico, no aleatorizado, de eficacia y seguridad de eritropoyetina en la disminución de transfusiones en el recién nacido pretérmino de muy bajo peso. Se incluyeron 72 neonatos con edad gestacional menor de 34 semanas posmenstruales, y peso al nacer menor o igual a 1 500 g, con más de 7 días posnatales e ingesta de 50 mL/kg/día. Resultados: todos recibieron eritropoyetina 300 U/kg, subcutánea, 3 veces/semana, hasta las 40 semanas de edad gestacional y suplemento de hierro y vitaminas. La eritropoyetina fue muy segura, solo se notificó con relación posible una retinopatía de la prematuridad, ligera y recuperada. Conclusiones: se transfundieron 7 pacientes (9,7 por ciento) en el curso del estudio. El uso tardío de eritropoyetina en el pretérmino de muy bajo peso confirma su eficacia y seguridad(AU)

Introduction: recombinant alpha erythropoietin is part of the treatment for anemia of prematurity. The use of this one in Cuba has been restricted and controversial as to schedule and dose. Methods: prospective, non-randomized multicenter assay on the safety and efficacy of erythropoietin in the reduction of blood transfusion in very-low-weight preterm newborn. Seventy two neonates with gestational age under 34 post-menstruation weeks, weighing equal or less than 1 500 g, over 7 days of life after birth and fed on 50 mL/kg/day were included in the study. Results: all of them received 300 U/kg erythropoietin by subcutaneous administration three times a week up to reaching 40 weeks of gestational age and an iron and vitamin supplement. Erythropoietin is very safe; it was just possibly related to slight retinopathy of prematurity, but overcome. Conclusions: seven patients were transfused (9.7 percent ) in the course of study. The late use of erythropoietin in very-low-weight preterm child confirms its efficacy and safety(AU)

Eficacia y seguridad de la eritropoyetina en la anemia de la prematuridad / Efficacy and safety of erythropoietin for anemia of prematurity

Introducción: la eritropoyetina alfa recombinante forma parte del tratamiento de la anemia de la prematuridad. En Cuba su uso ha sido limitado y controvertido en cuanto a esquema y dosis empleada. Métodos: ensayo clínico prospectivo, multicéntrico, no aleatorizado, de eficacia y seguridad de eritropoyetina en la disminución de transfusiones en el recién nacido pretérmino de muy bajo peso. Se incluyeron 72 neonatos con edad gestacional menor de 34 semanas posmenstruales, y peso al nacer menor o igual a 1 500 g, con más de 7 días posnatales e ingesta de 50 mL/kg/día. Resultados: todos recibieron eritropoyetina 300 U/kg, subcutánea, 3 veces/semana, hasta las 40 semanas de edad gestacional y suplemento de hierro y vitaminas. La eritropoyetina fue muy segura, solo se notificó con relación posible una retinopatía de la prematuridad, ligera y recuperada. Conclusiones: se transfundieron 7 pacientes (9,7 por ciento) en el curso del estudio. El uso tardío de eritropoyetina en el pretérmino de muy bajo peso confirma su eficacia y seguridad

Introduction: recombinant alpha erythropoietin is part of the treatment for anemia of prematurity. The use of this one in Cuba has been restricted and controversial as to schedule and dose. Methods: prospective, non-randomized multicenter assay on the safety and efficacy of erythropoietin in the reduction of blood transfusion in very-low-weight preterm newborn. Seventy two neonates with gestational age under 34 post-menstruation weeks, weighing equal or less than 1 500 g, over 7 days of life after birth and fed on 50 mL/kg/day were included in the study. Results: all of them received 300 U/kg erythropoietin by subcutaneous administration three times a week up to reaching 40 weeks of gestational age and an iron and vitamin supplement. Erythropoietin is very safe; it was just possibly related to slight retinopathy of prematurity, but overcome. Conclusions: seven patients were transfused (9.7 percent ) in the course of study. The late use of erythropoietin in very-low-weight preterm child confirms its efficacy and safety

Neonatal thrombocytopenia and platelets transfusion.

BACKGROUND: Neonates often develop thrombocytopenia at some time during hospital stay. Platelet transfusion are frequently given to them and are likely to result in unnecessary transfusion. MATERIAL AND METHODS: Thus, we analyzed thrombocytopenia in neonates, its prevalence, and relationship if any, between clinical condition and platelet transfusion in neonates, which would have been helpful in developing guidelines and/or protocols for platelet transfusion (and reducing the donor exposure) in neonates. RESULTS: A total of 870 neonates who were admitted in Neonatal Intensive Care Unit (NICU) with various morbidities had platelets count done; of these, 146 (16.7%) neonate revealed thrombocytopenia. DISCUSSION: Low birth weight babies (P 0.009) and babies born with mother having hypertension (P 0.04) showed significant thrombocytopenia. Neonates with intrauterine growth retardation (IUGR) diagnosed during antenatal screening showed lower platelet count (P 0.022). Neonates having associated illness, such as sepsis, gastrointestinal, and respiratory problems, and on vasopressor drugs were found to be associated with low platelet count. CONCLUSION: In our study, 16.40% of thrombocytopenic neonates required platelet transfusion either alone or with other blood component during their stay in NICU.