Donor Exposure Research Articles

Haemostatic management of cardiac surgical haemorrhage.

Almost 30,000 cardiopulmonary bypass operations are performed in the UK every year, consuming a considerable portion of the UK blood supply. Each year, in cardiac surgery, 90% of blood products are used by only 10% of patients, and over the past 25 years, much innovation and research has gone into improving peri-operative diagnosis and therapy for these patients. Visco-elastic tests performed at the bedside, with modifications to allow direct quantification of fibrinogen levels, are probably the biggest advancement. There is no clear advantage of thromboelastometry over thromboelastography, and the published literature remains scarce. Visco-elastic testing has recently been coupled with the systematic replacement of clotting factors by means of factor concentrates, with objective improvement in terms of blood loss, red blood cell usage and surgical re-exploration. The National Institute for Health and Care Excellence has reviewed the available evidence and recommended visco-elastic tests as cost effective in cardiac surgery. Factor concentrates, however, carry significant risks, particularly unnecessary donor exposures, potential selective over-correction of partial deficiencies and the possibility that the postoperative risk of venous thromboembolism is increased; as yet there are no data on risk-benefit analysis. There are a number of promising drugs used in topical haemostasis, but the requirement to apply these before major bleeding is manifest limits their use considerably. Hyperfibrinolysis is less important than in the past due to the wide spread adoption of antifibrinolytic agents and close intra-operative monitoring of heparin effect.

Effects of universal vs bedside leukoreductions on the alloimmunization to platelets and the platelet transfusion refractoriness

BackgroundMultiple platelet exposure induces anti-HLA and/or anti-HPA antibody production, which may cause platelet transfusion refractoriness (PTR). In Japan, the universal pre-storage leukocyte reduction (ULR) was fully implemented since 2006, but prior to ULR, in our institution, leukocyte reduction filters were routinely used at the bedside (bedside leukoreduction, BSLR) for all onco-hematological patients receiving multiple platelet transfusions. ObjectiveWe retrospectively compared patients receiving platelet transfusions in the era of ULR with those of BSLR era. Materials and methodsPatients of the BSLR group (409 cases) and the ULR group (586 cases) were compared in terms of alloimmunization and immunological PTR. The clinico-pathological features, including gender, history of pregnancy, number of exposed transfusion donors, periods of transfusion, and prior stem cell transplantation were compared, and the risk factors of alloimmunization were determined. ResultsThe antibody detection rate was significantly higher in the ULR compared to BSLR group (8.7% vs. 5.4%), as well as the immunological PTR rate (7.3% vs. 3.2%). By the multivariate analysis, female gender and the number of platelet donor exposure, but not universal leukoreduction or transfusion period, were found to be the risk factors strongly associated with alloantibody formation. ConclusionAlthough ULR may be superior to BSLR in terms of preventing non-hemolytic transfusion reactions, BSLR was found to be as effective as ULR in terms of preventing platelet alloimmunization and refractoriness. Thus, BSLR should be actively indicated as a realistic alternative in developing countries, before the universal leukoreduction is fully implemented.

P069 : ANALYSIS OF THE NON INHERITED HLA MATERNAL ANTIGENS-NIMA, IN THE BACECU-MEXICAN ALTRUISTIC CORD BLOOD BANK

Aim Selection for Cord Blood (CB) grafts for transplantation remains a challenge because of our inability to predict which mismatches will, and which will not, jeopardize patients’ survival. It has been shown that donor exposure to NIMA, can improve survival in unrelated CB transplantation and might reduce relapse, indicating that CB cells can mount an anti-leukemic effect. If this is confirmed, by matching for donors NIMAs in search algorithms of CB unrelated repositories, the probability of selecting a CBU with an optimal outcome will greatly increase. We focused on the analysis of CBU of the BACECU and of their mothers, looking into the HLA allele frequency (AF) of CBU and their mothers and allele and haplotype frequency (HF) of the NIMA. Methods DNA samples from the repository were HLA typed for A ∗ ; B ∗ ; C ∗ ; (two digits) DRB1 ∗ , DQB1 ∗ (HR), with the Luminex PCR-SSOP technology. The AF and haplotype HF was calculated using 82 mothers & CBU the SPSS17 software was used for the analyses. Analyses of HLA AF for CBU and their mothers; HLA AF for NIMAs and NIMA HF were performed as well as the presence of homozygous (H) alleles at any given locus in the mother. Results The prevalent NIMA, alleles (>5%) were: A ∗ 02, ∗ 68, ∗ 24, ∗ 03 ∗ ,01, ∗ 32, ∗ 29, ∗ 30; B ∗ 35, ∗ 39, ∗ 51, ∗ 40, ∗ 07, ∗ 44, ∗ 18, ∗ 52, ∗ 14; C ∗ 07, ∗ 04, ∗ 03, ∗ 12, ∗ 05, ∗ 15; DRB1 ∗ 08:02, ∗ 03:01, ∗ 01:01; ∗ 15:01, ∗ 04:01,16:02, ∗ 07:01, ∗ 04:07; DQB1 ∗ 04:02, ∗ 03:01; ∗ 03:02, ∗ 05:01, ∗ 06:02; the CB most frequent alleles (>5%) were: A ∗ 02, ∗ 24, ∗ 68, ∗ 01, ∗ 31; B ∗ 35, ∗ 14, ∗ 39, ∗ 44, ∗ 15, ∗ 51;C ∗ 07,03, ∗ 04, ∗ 08, ∗ 16;DRB1 ∗ 08:02,04:07, ∗ 01:02, ∗ 01:01, ∗ 07:01, ∗ 14:06; DQB1 ∗ 03:02, ∗ 03:01, ∗ 02:02, ∗ 05:01, ∗ 04:02. The three prevalent NIMA haplotypes (2.4%) were: 1. A ∗ 30-B ∗ 18-C ∗ 05-DRB1 ∗ 03:01-DQB1 ∗ 02:01; 2.- A ∗ 68-B ∗ 39-C ∗ 07-DRB1 ∗ 04:07-DQB1 ∗ 03:02(H); 3.- A ∗ 68-B ∗ 39-C ∗ 07-DRB1 ∗ 04:07-DQB1 ∗ 03:02. Among the NIMA haplotypes, 44%, carried at least one H allele at a given locus in the baby’s mother. The CB has a more Mestizo gene pool, than the NIMA. Conclusion Although many questions remain unanswered, in the light of these and the CB transplant results, it is worthwhile to identify NIMA matches as part of the selection process, to provide patients with permissive HLA mismatched but NIMA matched CBU, that may enhance the transplant outcome.

Using SDP; and so it came to Canada.

A solvent/detergent-treated plasma (SDP) Octaplas®was first introduced in Germany by Octapharma in 1991 and subsequently was used in other European countries. In the US, another version of SDP was introduced by Vitex in 1998 and was distributed by the American Red Cross but production there ceased in 2002–2003. In 2006, Octapharma’s SDP was licensed in Canada andmore recently in the US in 2013. For the Canadian Apheresis Group (CAG) the withdrawal of the SDP made by Vitex marked the end of our national study designed to compare SDP to cryo-poor plasma (CSP) in patients with thrombotic thrombocytopenic purpura (TTP). At that time, we were aware of “another” i.e. Octapharma source of SDP but were unable to convince funding authorities to allow us to continue with the trial using this material and so, after the entry of 61 patients, 34 of whom received Vitex SDP and 27 CSP, the study was stopped. While wewere unable to complete the comparative study we did generate a good deal of information concerning the biochemical and clinical parameters of the patients and this information was published in a paper published in 2013 [1]. There have long been concerns in this patient population about the use of plasma since they receive such very large volume exchange fluid in a very short period of time. In a 2008 assessment by the CAG it was determined that the average TTP patient received 40 L of plasma over the first 7 days of treatment however, recent data indicate a considerable increase in the volume of plasma required and therefore an increase in donor exposures. Massive plasma infusion has the drawback of exposing patients to a great number of plasma donors, which increases the risk of transfusion-transmitted infections. A product which provides a higher level of safety and reduces the incidence of adverse reactions would clearly benefit these patients. So the CAG has long had an interest in and an active voice for the use of a pathogen inactivated plasma (PIP). However, not all of the currently available PI plasmas are the same. Studies from Spain have indicated that methylene blue plasma is problematic for use in TTP patients [2]. Interestingly, of the other products available, SDP plasma, psoralen-treated plasma and the Mirasol® (riboflaventreated) plasma there has not actually been a RCT to support their use in TTP. However, several forms of PI are in widespread use in Europe and have been used in the treatment of patients with TTP with reported success. In fact, the last decade has seen a slow but steady shift from FFP to SDP on the part of most European countries as the advantages of PI plasma over frozen plasma are realized. A recent report by our group showing that hepatitis E was transmitted through pooled plasma products in the form of the Vitex SDP shows the importance of using a truly pathogen inactivated solution in treating these patients [3]. This is particularly important because current therapy for refractory and relapsing TTP patients involves the use of Rituximab which acts to inhibit B cells. The resultant immune suppression will make patients far more susceptible to infection so a major concern will be to ensure that the safest product is used, therefore pathogen inactivated products should be used in this patient population. In 2012 we held a Working Group meeting in Canada to consider the introduction of SDP in this country. A review done by Marie Scully at the time very nicely described the * Tel.: +1 613 748 9613. E-mail address: cag@cagcanada.ca.

Variant CJD and blood transfusion: are there additional cases?

In this study, we compare variant Creutzfeldt-Jakob disease (vCJD) cases definitely linked to blood transfusion, those with a history of blood transfusion in which no donor has developed vCJD and primary cases with no history of blood transfusion. The aim is to determine whether there are any differences in the demographics or clinical phenotype in these groups that might suggest additional cases of transfusion transmission of vCJD. All cases of vCJD who are old enough to donate blood (i.e. >17years old) are notified to the UKBTS at diagnosis, regardless of whether they are known to have a blood donation history. A search is then made for donor records and, if found, all components produced and issued to hospitals are identified and their fate determined. Recipient details are then checked against the NCJDRSU register to establish whether there is a match between these individuals and patients who have been diagnosed with vCJD. In the reverse study, attempts are made to trace the donors to all cases reported to have received a blood transfusion and donors' details are checked against the register to determine if any have developed vCJD. Of the 177 cases of vCJD diagnosed in the UK as of 1 February 2014, the TMER study identified 15 cases reported to have received a blood transfusion. Transfusion records were unavailable for 4 of these cases, all pre-1980, and in one other case there was no transfusion recorded in the medical notes. Transfusion records were found for 10 cases. One case transfused at symptom onset was excluded from this analysis. The mean age at onset of symptoms of the remaining nine transfusion recipients (four female and five male) was 42·9years; 57·6years in the three known transfusion-transmitted cases and 35·5years in the six not linked cases. In one of these cases, details of components transfused were unavailable, and the remaining five cases received a total of 116 donor exposures with 112 donors identified, none of whom is known to have developed clinical vCJD. To date, five of the 112 identified donors have died and none was certified as dying of vCJD or any other neurological disorder. Two of the transfusion-transmitted cases did not fulfil diagnostic criteria for probable vCJD during life but were confirmed at post-mortem. Both cases were in the older age range (68 and 74years, respectively), and neither had a positive MRI brain scan. The remaining cases all fulfilled the criteria for the diagnosis of vCJD in life, but two of these had atypical features and were older than the expected age at onset for vCJD. In conclusion, it is possible that one or more of the vCJD cases that received a blood transfusion derived from an individual not known to have vCJD were infected by the blood transfusion. However, the evidence for this is weak, and the absence of a past history of transfusion in most cases of vCJD excludes a large number of unrecognised transfusion-transmitted cases.

Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.

Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia. To assess the effectiveness and safety of early initiation of EPO or darepoetin (initiated before eight days after birth) in reducing red blood cell (RBC) transfusions in preterm and/orlow birth weight infants. The Cochrane Library, MEDLINE, EMBASE, CINAHL, reference lists of identified trials and reviews, Pediatric Academic Societies Annual meetings 2000 to 2013 (Abstracts2View(TM)) and clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp) were searched in July 2013. Randomised or quasi-randomised controlled trials of early (< eight days of age) initiation of EPO treatment versus placebo or no intervention in preterm and/or low birth weightinfants. The methods of the Neonatal Cochrane Review Group were used. The updated review includes 27 studies enrolling 2209 infants. One study enrolling infants at a mean age of > eight days and one duplicate publication were excluded. One new study using darepoetin was identified.Early EPO reduced the risk of the 'use of one or more RBC transfusions' (typical risk ratio (RR) 0.79, 95% confidence interval (CI) 0.73 to 0.85; typical risk difference (RD) -0.14, 95% CI -0.18 to -0.10; I(2) = 54% for both; number needed to treat to benefit (NNTB) 7, 95% CI 6 to 10; 16 studies, 1661 infants).The total volume of RBCs transfused per infant was reduced (typical mean difference (MD) 7 mL/kg, 95% CI -12 to - 2; I(2) = 63%; 7 studies, 581 infants). The number of RBC transfusions per infant was minimally reduced (typical MD -0.27, 95% CI -0.42 to -0.12; I(2) = 64%; 13 studies, 951 infants). The number of donors to whom the infants were exposed was significantly reduced (MD-0.54, 95% CI -0.89 to -0.20; I(2) = 0%; 3 studies, 254 infants).There was a non-significant increase in the risk of stage ≥ 3 retinopathy of prematurity (ROP) with early EPO (typical RR 1.37, 95% CI 0.87 to 2.17; I(2) = 0%; typical RD 0.03, 95% CI -0.01 to 0.06; I(2) = 29%; 7 studies, 801 infants). A post hoc analysis including all studies that reported on ROP stage ≥ 3, regardless of the age of the infant when EPO treatment was started, showed a significantly increased typical RR of 1.48 (95% CI 1.02 to 2.13; P = 0.04; I(2) = 0%) and typical RD of 0.03 (95% CI 0.00 to 0.06; P = 0.03; I(2) = 50%; 10 studies, 1303 infants) with a number needed to treat to harm (NNTH) of 33 (95% CI 17 to infinity). In an Italian study in which the authors compared the use of early intravenous EPO with subcutaneous EPO the overall incidence of stage ≥ 3 was 15%, similar to the incidence of 17% in the study by Romagnoli and co-workers.The rates for mortality and morbidities including intraventricular haemorrhage and necrotizing enterocolitis were not significantly changed by early EPO treatment. Neurodevelopmental outcomes at 18 to 22 months varied. Early administration of EPO reduces the use of RBC transfusions, the volume of RBCs transfused, and donor exposure after study entry. The small reductions are likely to be of limited clinical importance. Donor exposure is probably not avoided since all but one study included infants who had received RBC transfusions prior to trial entry. In this update there was no significant increase in the rate of ROP (stage ≥ 3) for studies that initiated EPO treatment at less than eight days of age. In a post hoc analysis including all studies that reported on ROP stage ≥ 3 regardless of age at initiation of treatment there was an increased risk of ROP. The rates for mortality and morbidities including intraventricular haemorrhage and necrotizing enterocolitis were not significantly changed by early EPO treatment. Neurodevelopmental outcomes at 18 to 22 months vary in the studies published to date. Ongoing research should deal with the issue of ROP and evaluate current clinical practice that will limit donor exposure. Due to the limited benefits and the possibly increased risk of ROP, administration of EPO is not recommended. Darbepoetin requires further study. The possible neuroprotective role of EPO in neonates will be reviewed in separate Cochrane reviews.

Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.

Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia. To assess the effectiveness and safety of late initiation of erythropoietin (EPO) between eight and 28 days after birth, in reducing the use of red blood cell (RBC) transfusions in preterm and/or low birth weight infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL in July 2013. Additional searches included the Pediatric Academic Societies Annual Meetings from 2000 to 2013 (Abstracts2View™) and clinical trials registries (www.clinicaltrials.gov; www.controlled-trials.com; and who.int/ictrp/en). For this update we moved one study from the early EPO review to this late EPO review. Randomised or quasi-randomised controlled trials of late initiation of EPO treatment (started at ≥ eight days of age) versus placebo or no intervention in preterm (< 37 weeks) and/or low birth weight (< 2500 g) neonates. We performed data collection and analyses in accordance with the methods of the Cochrane Neonatal Review Group. We include 30 studies (31 comparisons) randomising 1591 preterm infants. Literature searches in 2013 did not identify any new study for inclusion. For this update we moved one study enrolling 230 infants from the early EPO review to this late EPO review.Most included trials were of small sample size. The meta-analysis showed a significant effect of the use of one or more RBC transfusions (20 studies (n = 1142); typical risk ratio (RR) 0.71, 95% confidence interval (CI) 0.64 to 0.79; typical risk difference (RD) -0.17, 95% CI -0.22 to -0.12; typical number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 5 to 8). There was moderate heterogeneity for this outcome (RR I² = 68%; RD I² = 60%). We obtained similar results in secondary analyses based on different combinations of high/low doses of EPO and iron supplementation. There was no significant reduction in the total volume (mL/kg) of blood transfused per infant [typical mean difference (MD) -1.6 mL/kg, 95% CI -5.8 to 2.6); 5 studies, 197 infants]. There was high heterogeneity for this outcome (I² = 92%). There was a significant reduction in the number of transfusions per infant (11 studies enrolling 817 infants; typical MD -0.22, 95% CI -0.38 to -0.06). There was high heterogeneity for this outcome (I² = 94%).Three studies including 404 infants reported on retinopathy of prematurity (ROP) (all stages or stage not reported), with a typical RR 1.27 (95% CI 0.99 to 1.64) and a typical RD of 0.09 (95% CI -0.00 to 0.18). There was high heterogeneity for this outcome for both RR (I² = 83%) and RD (I² = 82%). Three trials enrolling 442 infants reported on ROP (stage ≥ 3). The typical RR was 1.73 (95% CI 0.92 to 3.24) and the typical RD was 0.05 (95% CI -0.01 to 0.10). There was minimal heterogeneity for this outcome for RR (I² = 18%) but high heterogeneity for RD (I² = 79%). There were no significant differences in other clinical outcomes. There was no reduction in necrotizing enterocolitis in spite of a reduction in the use of RBC transfusions. Long-term neurodevelopmental outcomes were not reported. Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant (< 1 transfusion per infant) but not the total volume (ml/kg) of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes except for a trend in increased risk for ROP. Further research of the use of late EPO treatment to prevent donor exposure is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment. The use of satellite packs (dividing one unit of donor blood into many smaller aliquots) may reduce donor exposure.

G227(P) Reducing donor exposure from blood transfusions in preterm babies: improving the use of satellite pack

AimsPremature infants frequently require multiple red blood cell (RBC) transfusions. The practice of splitting a single adult unit into satellite packs has been widely adopted to reduce the risks of...

G214(P) Reducing transfusion donor exposure in preterm babies: good communication is vital

BackgroundPreterm infants frequently require multiple blood transfusions. Splitting adult units into 6–8 satellite packs has been universally adopted by neonatal units to reduce donor exposure. Our NICU guideline is to...

Blood support for pediatric surgery

With the advances in surgical technique, increasingly complicated and knotty surgeries were performed on neonatal and pediatric patients, and the success of many of these surgeries are ensured by an adequate and safe blood supply.Autologous and/or allogeneic blood may be used, depending upon the anticipated blood loss, types of components required, and urgency of surgery.However, in all cases, every attempt should be made to minimize the number of donor exposures to reduce the risk of transfusion, for dangers of transfusion having been payed more attention.The strategy and practice of blood support for pediatric surgery show very important. Key words: Pediatric Surgery; Transfusion; Blood

Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products

Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products

Minimizing Transfusions in Primary Cranial Vault Remodeling

Cranial vault remodeling (CVR) for craniosynostosis is a procedure with the potential for significant blood loss. Aminocaproic acid (ACA) has been used at our institution during CVR for its antifibrinolytic effects. The purpose of this study was to investigate the effect of ACA on blood loss and transfusion rates during primary CVR. Three hundred eighty-three patients with craniosynostosis underwent primary CVR at a single institution by a single surgeon over 15 years. Patients were included if they received either ACA or no antifibrinolytic. The estimated blood loss (EBL) and volume of blood transfused was recorded. Thrombotic-related complications were identified. Comparisons were made between subgroups using independent Student t test and Fisher exact test. Among the study population, 148 patients met inclusion criteria. ACA was given to 30 patients, while 118 patients received no antifibrinolytic. There was no difference in the average intraoperative EBL between the ACA (322 mL) and control groups (327 mL, P > 0.05). Additionally, the incidence of transfusion was not significantly different between subgroups (97% vs. 86%, respectively, P > 0.05). Patients treated with ACA, however, received lower average perioperative transfusion volumes (25.5 mL/kg) compared to control patients (53.3 mL/kg, P < 0.0001). Furthermore, patients in the ACA subgroup were less likely to require a second unit of blood (21% vs. 43%, P < 0.0001) and therefore had fewer exposures to donor blood antigens (ARR = 22%, NNT = 4.6). The use of intraoperative ACA minimizes blood transfusion volumes and donor exposures in children who undergo primary CVR for craniosynostosis. Antifibrinolytics should be considered for routine use in pediatric craniofacial surgery.

Transfusion Practices and Infections At Four Level III Neonatal Intensive Care Units

IntroductionTransfusions of packed red blood cell (pRBC) units to infants in Neonatal Intensive Care Units (NICUs) may predispose neonates to healthcare-associated infections (HAIs). We compared neonatal pRBC transfusion practices at four NICUs (Morgan Stanley Children's Hospital of NewYork-Presbyterian, Columbia University Medical Center, Komansky Children's Hospital of Weill Cornell Medical Center, Christiana Care Health System, and Children's Hospital of Philadelphia). In addition, because prolonged refrigerator storage of pRBC may further predispose to HAIs, we tested the hypothesis that an increased mean RBC storage age was associated with a greater risk of infections. DesignThe interdisciplinary NICU Antimicrobial Prescribing (iNAP) study was conducted in four Level III NICUs from May 2009 to April 2012 to assess HAIs and improve antimicrobial prescribing in NICUs. Eligible infants were admitted <7 days of age and hospitalized ≥4 days. Demographic (e.g., sex, birth weight [BW]) and clinical data (e.g., HAIs and surgical procedures) were collected. HAI included culture negative sepsis defined by treating clinicians, necrotizing enterocolitis, or bacteremia treated for ≥ 4 days. pRBC transfusions were collected from blood bank records at each site. Descriptive statistics were performed using GraphPad Prism 6. ResultsAll sites used irradiated, leukoreduced, CMV negative pRBCs and practiced donor limitation. Blood bank preparation procedures were similar at all sites except that one site stored 3% of units in CPDA-1 in addition to units stored in Additive Solutions (AS), and another site irradiated the parent unit instead of the aliquot; the other sites irradiated the aliquot prior to release. During the study period, 6411 pRBC transfusions were administered to 1381 (21.5%) of 6184 enrolled infants. The transfusion rate was 12.6%, 37.3%, 16.7%, and 25.1% at sites 1-4, respectively. The rate of transfusion by normal BW (≥2500g), low BW (1500-2499g), very LBW (<1500g), and extremely LBW (<1000g) was 0.8, 0.4, 2.8, and 5.5 per patient, respectively. Transfused infants received an average of 4.7 transfusions (range 1-63; average of 3.5, 4.5, 4.5, and 6.0 transfusions at each respective site) with a mean donor exposure of 2.1 (range 1-23). Overall, 50% of pRBC transfusions occurred in the first 17 days of life and 34% occurred during the first week of life. Surgical and post-surgical transfusions accounted for 1389 (21.7%) of 6411 transfusions in 486 (35%) of 1381 transfused infants. Infants undergoing congenital diaphragmatic hernia repair required the most transfusions; 34 infants received 537 ECMO-related transfusions. The average storage age of the pRBC transfused was 16.1 days, but differed by site (12.5, 14.6, 16.7, 19.9 days for each site, respectively, p< 0.001 by Kruskal-Wallis test with Dunns Multiple Comparison Test) and by aliquot (1st-5th aliquot average age 12, 16, 19, 21, and 23 days, respectively). The average age of units transfused in infants without HAIs (n=5693) was 15.2 days; while the average age of units transfused in infants with HAIs (n=491) that developed after transfusion was 15.4 (p=0.04). An ecological study comparing all sites did not find a significant association between the average storage age of units transfused per site (excluding units transfused after onset of infection) and the proportion of neonates with HAIs at the site (R2=0.29; p=0.46; see Figure). [Display omitted] ConclusionsTo our knowledge, this is the largest cohort study of neonatal transfusion practices in Level III NICUs. Transfusion practices were similar at each site. The average storage age of transfused pRBC units varied among the four sites; however, the mean RBC storage age of RBCs transfused to patients with or without HAIs was not markedly different and hospitals with a longer mean storage age did not have a higher proportion of neonates with HAIs. Further analysis is needed to explore the relationship between pRBC storage and HAIs, while controlling for differences in patient characteristics. Disclosures:No relevant conflicts of interest to declare.

Update: Advances in Pediatric Cardiac Intensive Care

Update: Advances in Pediatric Cardiac Intensive Care

Restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants: A systematic review and meta‐analysis

A systematic review was conducted to examine the effects of restrictive versus liberal red blood cell (RBC) transfusion thresholds on clinically important outcomes in very low birth weight (VLBW) infants. Randomised controlled trials (RCTs) of varying RBC transfusion thresholds in VLBW infants were identified by searching MEDLINE, EMBASE, CINAHL, all of the Cochrane Library and other supplementary sources. Selected studies included one of the following outcomes: total number of red blood cell transfusions, donor exposure rate, cranial ultrasonographically diagnosed brain injury, retinopathy of prematurity, bronchopulmonary dysplasia, necrotising enterocolitis or death. Studies to be included were selected by two reviewers who also assessed the risk of bias of each trial. Data extraction and analyses were independently performed by two reviewers. All data were analysed using RevMan 5. Six RCTs were identified. One trial did not meet the inclusion criteria, while two had inadequate methodological quality. Pooled analysis of two trials showed that the restrictive transfusion group received a significantly lower mean number of transfusions per infant (mean difference (MD) -1.35, 95% confidence interval (CI) [-2.61, -0.09]) and donor exposure rate (MD -0.54, 95% CI [-0.93, -0.15]). No other statistically significant differences were observed. Restrictive RBC transfusion thresholds in VLBW infants may be utilised without incurring clinically important increases in the risk of death or major short-term neonatal morbidities.

Cardiac critical care

The sustained decline in mortality following congenital heart surgery, while important, also has resulted in an emerging focus upon the use of processes and technological developments to reduce early postoperative morbidity. We summarize here recent efforts within the field of pediatric cardiac intensive care to optimize outcomes associated with the perioperative management of the child with congenital heart disease. Goal-directed and protocol-driven therapy targeting optimization of oxygen delivery improves outcomes in the management of many populations of critically ill patients, and is now increasingly used following congenital heart surgery with a low associated incidence of organ failure and favorable early survival. Restrictive blood product transfusion practices following congenital heart surgery are showing promise in reducing donor exposures and transfusion-associated morbidities without a resulting increase in end organ dysfunction. Technological developments are affording noninvasive opportunities for earlier recognition and intervention in the deteriorating child, while also providing means for support of the failing myocardium, both in an acute setting during cardiopulmonary resuscitation, and among patients with end-stage heart failure requiring longer-term mechanical circulatory support. Multi-institutional, prospective evaluation of perioperative management practices, along with patient-specific, integrated electronic health information, provides unique opportunities for investigators to identify and test both processes and technological tools in confronting the most challenging aspects of early postoperative management following congenital heart surgery.

Reduction of exposure to blood donors in preterm infants submitted to red blood cell transfusions using pediatric satellite packs

OBJECTIVE: In preterm newborn infants transfused with erythrocytes stored up to 28 days, to compare the reduction of blood donor exposure in two groups of infants classified according to birth weight. METHODS: A prospective study was conducted with preterm infants with birth weight <1000g (Group 1) and 1000-1499g (Group 2), born between April, 2008 and December, 2009. Neonates submitted to exchange transfusions, emergency erythrocyte transfusion, or those who died in the first 24 hours of life were excluded. Transfusions were indicated according to the local guideline using pediatric transfusion satellite bags. Demographic and clinical data, besides number of transfusions and donors were assessed. . Logistic regression analysis was performed to determine factors associated with multiple transfusions. RESULTS: 30 and 48 neonates were included in Groups 1 and 2, respectively. The percentage of newborns with more than one erythrocyte transfusion (90 versus 11%), the median number of transfusions (3 versus 1) and the median of blood donors (2 versus 1) were higher in Group 1 (p<0.001), compared to Group 2. Among those with multiple transfusions, 14 (82%) and one (50%) presented 50% reduction in the number of blood donors, respectively in Groups 1 and 2. Factors associated with multiple transfusions were: birth weight <1000g (OR 11.91; 95%CI 2.14-66.27) and presence of arterial umbilical catheter (OR 8.59; 95%CI 1.94-38.13), adjusted for confounders. CONCLUSIONS: The efficacy of pediatrics satellites bags on blood donor reduction was higher in preterm infants with birth weight <1000g.

A Randomized, Masked, Placebo-Controlled Study of Darbepoetin Alfa in Preterm Infants

A novel erythropoiesis stimulating agent (ESA), darbepoetin alfa (Darbe), increases hematocrit in anemic adults when administered every 1 to 3 weeks. Weekly Darbe dosing has not been evaluated in preterm infants. We hypothesized that infants would respond to Darbe by decreasing transfusion needs compared with placebo, with less-frequent dosing than erythropoietin (Epo). Preterm infants 500 to 1250 g birth weight and ≤48 hours of age were randomized to Darbe (10 μg/kg, 1 time per week subcutaneously), Epo (400 U/kg, 3 times per week subcutaneously) or placebo (sham dosing) through 35 weeks' gestation. All received supplemental iron, folate, and vitamin E, and were transfused according to protocol. Transfusions (primary outcome), complete blood counts, absolute reticulocyte counts (ARCs), phlebotomy losses, and adverse events were recorded. A total of 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation, 51 ± 25 hours of age at first dose) were enrolled. Infants in the Darbe and Epo groups received significantly fewer transfusions (P = .015) and were exposed to fewer donors (P = .044) than the placebo group (Darbe: 1.2 ± 2.4 transfusions and 0.7 ± 1.2 donors per infant; Epo: 1.2 ± 1.6 transfusions and 0.8 ± 1.0 donors per infant; placebo: 2.4 ± 2.9 transfusions and 1.2 ± 1.3 donors per infant). Hematocrit and ARC were higher in the Darbe and Epo groups compared with placebo (P = .001, Darbe and Epo versus placebo for both hematocrit and ARCs). Morbidities were similar among groups, including the incidence of retinopathy of prematurity. Infants receiving Darbe or Epo received fewer transfusions and fewer donor exposures, and fewer injections were given to Darbe recipients. Darbepoetin and Epo successfully serve as adjuncts to transfusions in maintaining red cell mass in preterm infants.

Vacuum-Assisted Venous Drainage, Angel or Demon: PRO?

Vacuum-assisted venous drainage (VAVD) was proposed to optimize venous drainage during bypass through femoral venous cannulation. It is currently used in both adult and pediatric surgery when siphon gravity venous drainage is suboptimal. In pediatric surgery, the major advantages of VAVD are a significant decrease in cardiopulmonary bypass prime volume and an improved drainage with all collateral benefits. To limit gravity drainage, we use a two-level heart–lung machine dedicated to pediatric perfusion. The top level of the cardiotomy reservoir is positioned at the patient atrial level, making it possible to downsize the length and diameter of venous and arterial lines. Since 2008, a negative pressure of approximately −30 mmHg has been used for all patients. Initiation of bypass is performed in a classical way with a cardiotomy reservoir open; vacuum is added as soon as the maximal gravity drainage is reached. During bypass, when the blood level in the reservoir decreases to the safety limit level, a small increase in negative pressure is used to improve venous drainage. For weaning from bypass, the negative pressure is gradually decreased to zero, then the reservoir is opened and the venous line progressively closed. Prime volumes were significantly reduced to 100 mL for small neonates, 125 mL for infants, and 175 mL for older children with flow up to 1.5 L/min−1. A low prime volume is expected to improve blood conservation and decrease donor exposure, prevent drawbacks of transfusion (immunomodulation, infection), increase the incidence of blood-free surgery in smaller babies, and decrease whole body systemic inflammation by decreasing surface of foreign material in contact with blood and inflammation associated with blood transfusion. The main drawbacks described have been retrograde flow in the venous line with cerebral air embolus and an increased incidence of gaseous microemboli. These drawbacks are avoidable through appropriate training of perfusionists. When negative pressure is “reasonable,” complications are more theoretical than significant in clinical practice. A technique with a benefit/drawback ratio of 1:0 is utopian, but the advantages of VAVD far outweigh any potential drawbacks when applied properly.

Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion

Platelet (PLT) and plasma transfusion remain the mainstay hemostatic therapy for perioperative bleeding. Several studies have indicated that acquired fibrinogen (FIB) deficiency can be the primary cause of bleeding after cardiac surgery. The aim of this study was to compare hematologic and transfusion profiles between the first-line FIB replacement and PLT transfusion in post-cardiac surgical bleeding. In this prospective, randomized, open-label study, 20 adult patients who underwent valve replacement or repair and fulfilled preset visual bleeding scale were randomized to 4 g of FIB or 1 unit of apheresis PLTs. Primary endpoints included hemostatic condition in the surgical field and 24-hour hemostatic product usage. Hematologic data, clinical outcome, and safety data were collected up to the 28th day postoperative visit. In patients who received the first-line FIB concentrate (n = 10), the visual bleeding scale improved after intervention, and the incidence of PLT transfusion and total plasma donor exposure were lower compared to the PLT group (n = 10). Postintervention FIB level was statistically higher (209 mg/dL vs. 165 mg/dL) in the FIB group than in the PLT group, but PLT count and prothrombin were lower. There were no statistical differences in the postoperative blood loss and red blood cell transfusion between two groups. Our preliminary data indicate that the primary FIB replacement may potentially reduce the incidence of PLT transfusion and the number of donor exposures. Plasma FIB level of 200 mg/dL is attainable with a single dose of 4 g, and this level seems to mitigate bleeding despite moderately decreased thrombin generation.