Large-volume Transfusion Research Articles

Separate Effect of Perioperative Recombinant Human Factor VIIa Administration and Packed Red Blood Cell Transfusions on Midterm Survival in Lung Transplantation Recipients

ObjectiveThe purpose of this study was to determine the relationship between blood product transfusion, with or without recombinant human activated factor VIIa, and survival after lung transplantation. DesignRetrospective analysis of a single center with follow-up out to 6 years post-transplantation. SettingSingle-center academic lung transplantation program. ParticipantsThe study comprised 265 adult patients who underwent single or bilateral sequential lung transplantation from March 2011 to June 2017. InterventionsOverall survival using Kaplan-Meier curves was compared among the following 3 cohorts: those not transfused with blood products, those transfused with blood products, and those given blood products and recombinant human activated factor VIIa. Cox proportional hazards regression was used to estimate hazard ratios (HRs), confidence intervals (CIs), and p values. Measurements and Main ResultsSeventy-eight patients received no packed red blood cell transfusions, 149 received packed red blood cell transfusions, and 38 received both packed red blood cell transfusions and recombinant human activated factor VII. Packed red blood cell transfusion was associated with an increased risk of mortality that did not reach statistical significance (HR 2.168, CI 0.978-4.805; p = 0.057). Additional packed red blood cells beyond 15 U were associated with worsened survival (HR 1.363, CI 1.137-1.633; p = 0.001), but recombinant human activated factor VIIa did not increase the risk of mortality. ConclusionBlood product transfusion during and after lung transplantation is associated with decreased survival, especially with large-volume transfusions. Survival is not worse with recombinant human activated factor VIIa administration, but additional studies are needed to determine whether recombinant human activated factor VIIa administration reduces the need for blood product transfusions.

Considerations for Pediatric Heart Programs During COVID-19: Recommendations From the Congenital Cardiac Anesthesia Society.

Considerations for Pediatric Heart Programs During COVID-19: Recommendations From the Congenital Cardiac Anesthesia Society.

P4736The Prognostic Impact of Volume Substitution on Cardiac Strain and the Development of Postoperative Atrial Fibrillation after Cardiac Surgery

Abstract Background Postoperative atrial fibrillation (POAF) represents a common complication after cardiac valve or coronary artery bypass surgery. Etiologically, multifactorial causes such as the patients' age, weight, comorbidities or local remodeling proved a strong association with this common arrhythmia. While strain of atrial tissue is known to induce atrial fibrillating impulses, less attention has been paid to potentially strain-promoting values during the peri- and post-operative period. Therefore, we aimed to determine the association of peri- and post-operative volume substitution on markers of cardiac strain and subsequently its impact on the promotion and development of POAF. Methods In this prospective observational study 271 patients undergoing elective cardiac surgery in our Medical University were enrolled (median age: 69 years [IQR: 60–75 years]; 195 [72%] male gender). Intra- and post-operative data was collected from anesthesiologic and intensive care unit protocols. Multivariate binary logistic regression analysis was used to identify the prognostic value of volume substitution on the development of POAF. Results A total of 123 (45.4%) individuals developed POAF. The average intra-operative transfusion volume was significantly elevated in the POAF subgroup (605.6ml [POAF] vs. 227.1ml [non-POAF]; p<0.001). Moreover, the fluid balance within the first 24 hours after surgery was significantly higher in patients developing POAF (+1129.6 ml [POAF] vs. +544.9 ml [non-POAF]; p=0.044). We found that N-terminal pro brain natriuretic peptide (NT-proBNP) values were significantly elevated in patients that received any volume substitution (2860.0 pg/mL [Transfusion] vs. 1486.5 pg/mL [no-Transfusion]; p=0.002). In line with those results, the postoperative fluid balance was also found to have a direct and significant correlation with postoperative NT-ProBNP values (r=0.287, p=0.002). Of note, the amount of substituted volume proved to be a strong and independent predictor for POAF with an adjusted odds-ratio (OR) per one standard deviation (1-SD) of 2.49 (95% CI: 1.25–4.96; p=0.009). Conclusion Within the present analysis we were able to demonstrate that substitution of larger transfusion volumes presents a strong and independent predictor for the development of POAF. Via the observed distinct association with NT-proBNP values, it can reasonably be assumed that post-operative atrial fibrillating impulses are triggered via volume-induced cardiac strain.

A Rotational Thromboelastometry Driven Transfusion Strategy Reduces Allogenic Blood Transfusion During Open Thoraco-abdominal Aortic Aneurysm Repair: A Propensity Score Matched Study

Open repair of thoraco-abdominal aortic aneurysm (TAAA) is a challenging procedure, associated with high rates of peri-operative bleeding and blood product transfusions. A large intra-operative volume transfusion has been associated with higher in hospital mortality and prolonged mechanical ventilation. A propensity score matched study was carried out to assess whether the introduction of a rotational thromboelastometry (ROTEM) based transfusion strategy reduces allogenic blood transfusion and affects morbidity in patients undergoing open TAAA repair. All patients undergoing open TAAA repair at the San Raffaele Scientific Institute between 2009 and 2017 were included. Until 2016, a protocol based on estimated blood loss and conventional coagulation tests was used. After March 2016 a ROTEM guided transfusion protocol was developed and adopted. To account for selection bias, propensity score matching was performed. Five hundred and forty-seven consecutive patients were included. After propensity score matching, 77 patients in the ROTEM algorithm group were successfully matched with 77 patients in the standard algorithm group. Patients managed with ROTEM received fewer red blood cells units (3.5 [range 0–11] vs. 4 [range 0–17]; p = .026) and a lower volume of fresh frozen plasma (286 ± 496 vs. 2,050 ± 1,120; p < .001). In addition, fewer patients received fresh frozen plasma (35% vs. 97%; p < .001). Patients in the ROTEM group showed a significant decrease in the occurrence of pulmonary complications (44% vs. 83%; p = .01). Cost analysis showed a relevant reduction of per-patient expense after the introduction of ROTEM (€834 ± €577 vs. €1,285 ± €851; p < .001) A ROTEM guided transfusion strategy significantly limited the quantity of transfused blood products during open TAAA repair, improving clinical outcomes while reducing costs, allowing for better resource distribution in a setting where blood loss is relevant.

Editor's Choice – A Rotational Thromboelastometry Driven Transfusion Strategy Reduces Allogenic Blood Transfusion During Open Thoraco-abdominal Aortic Aneurysm Repair: A Propensity Score Matched Study

Open repair of thoraco-abdominal aortic aneurysm (TAAA) is a challenging procedure, associated with high rates of peri-operative bleeding and blood product transfusions. A large intra-operative volume transfusion has been associated with higher in hospital mortality and prolonged mechanical ventilation. A propensity score matched study was carried out to assess whether the introduction of a rotational thromboelastometry (ROTEM) based transfusion strategy reduces allogenic blood transfusion and affects morbidity in patients undergoing open TAAA repair. All patients undergoing open TAAA repair at the San Raffaele Scientific Institute between 2009 and 2017 were included. Until 2016, a protocol based on estimated blood loss and conventional coagulation tests was used. After March 2016 a ROTEM guided transfusion protocol was developed and adopted. To account for selection bias, propensity score matching was performed. Five hundred and forty-seven consecutive patients were included. After propensity score matching, 77 patients in the ROTEM algorithm group were successfully matched with 77 patients in the standard algorithm group. Patients managed with ROTEM received fewer red blood cells units (3.5 [range 0-11] vs. 4 [range 0-17]; p=.026) and a lower volume of fresh frozen plasma (286±496 vs. 2,050±1,120; p<.001). In addition, fewer patients received fresh frozen plasma (35% vs. 97%; p<.001). Patients in the ROTEM group showed a significant decrease in the occurrence of pulmonary complications (44% vs. 83%; p=.01). Cost analysis showed a relevant reduction of per-patient expense after the introduction of ROTEM (€834±€577 vs. €1,285±€851; p<.001) CONCLUSION: A ROTEM guided transfusion strategy significantly limited the quantity of transfused blood products during open TAAA repair, improving clinical outcomes while reducing costs, allowing for better resource distribution in a setting where blood loss is relevant.

Blood transfusion therapy for β-thalassemia major and hemoglobin E β-thalassemia: Adequacy, trends, and determinants in Sri Lanka.

Regular blood transfusion therapy still remains the cornerstone in the management of β-thalassemia. Although recommendations are clear for patients with β-thalassemia major, uniform transfusion guidelines are lacking for patients with hemoglobin E β-thalassemia. In this study, we aim to describe the adequacy, trends, and determinants of blood transfusion therapy in a large cohort of pediatric patients with β-thalassemia major and hemoglobin E β-thalassemia. This cross-sectional study was performed among all regularly transfused patents with β-thalassemia aged 2 to 18 years attending three large thalassemia centers in Sri Lanka. Data were collected using an interviewer-administered questionnaire, perusal of clinical records, and physical examination of patients by trained doctors. A total of 328 patients (male 47%) were recruited; 83% had β-thalassemia major, whereas 16% had hemoglobin E β-thalassemia. Sixty-one percent of patients had low pretransfusion hemoglobin levels (<9.0g/dL) despite receiving high transfusion volumes (>200mL/kg/year) by a majority (56%). Median pretransfusion hemoglobin was significantly lower in patients with hemoglobin E β-thalassemia compared with β-thalassemia major (P<0.001); however, there was no difference in requirement for high transfusion volumes over 200mL/kg/year in both groups (P=0.14). Hepatomegaly and splenomegaly were more common in hemoglobin E β-thalassemia and were associated with lower pretransfusion hemoglobin. Transfusion requirements were higher among patients with hepatitis C and in those who are underweight. Over 60% of regularly transfused patients with β-thalassemia have low pretransfusion hemoglobin levels despite receiving large transfusion volumes. Patients with hemoglobin E β-thalassemia are undertransfused and specific recommendations should be developed to guide transfusions in these patients.

Fibrinogen Concentrate Vs. Cryoprecipitate for Acquired Hypofibrinogenemia in Cardiac Surgery — the FIBRES Study

Introduction: Cardiac surgery involving cardiopulmonary bypass (CPB) is associated with coagulopathy and excessive bleeding. This often requires the transfusion of large volumes of allogeneic blood products and is linked to an increased risk of adverse outcomes. A primary cause of coagulopathy is acquired hypofibrinogenemia; when fibrinogen levels drop below 1.5-2 mg/L, fibrinogen supplementation is required to maintain hemostasis. The FIBrinogen REplenishment in Surgery (FIBRES) study aims to compare the standard intervention, cryoprecipitate, with a new highly purified, double virus-inactivated human fibrinogen concentrate.Methods: The FIBRES study (NCT03037424) is a pragmatic, multicenter, active-control, randomized, single-blinded, non-inferiority phase 3 trial in adult patients undergoing cardiac surgery with CPB. The study will enroll patients with clinically significant bleeding associated with acquired hypofibrinogenemia. Patients for whom fibrinogen supplementation is ordered within 24 hours of surgery will be randomized to receive fibrinogen concentrate (4 g; Fibryga; Octapharma) or cryoprecipitate (10 units; dose equivalent to 4 g fibrinogen concentrate) (Figure 1). All randomized patients will receive fibrinogen supplementation as clinically indicated. Owing to the emergency nature of the clinical setting, patient consent at the point of randomization will be waived, with written informed consent obtained within 24-48 hours thereafter. The primary outcome is total allogeneic blood products (red blood cells, plasma, platelets) administered within the first 24 hours of surgery. Secondary outcomes include blood product use within 7 days, incidence of major bleeding within 24 hours, fibrinogen levels, and adverse events (AEs) and serious AEs within 28 days. Enrolment of 1,200 patients will provide >90% power to demonstrate non-inferiority, assuming a 20% non-inferiority margin, ≥550 patients per group, and an approximate 10% drop-out rate. One pre-planned interim analysis will be conducted after data are available for 600 evaluable patients with the option to stop early for futility or overwhelming efficacy. The pragmatic design and treatment algorithm align with standard practice, aiding adherence and generalizability.Results: To date, 530 patients have been treated across 11 sites. An IDMEAC review of safety has been performed every 100 patients enrolled, with the recommendation to continue as planned each time. The study is expected to complete in late 2018, with results available in early 2019.Conclusions: The FIBRES study is the largest randomized study to date of fibrinogen concentrate versus cryoprecipitate in adult cardiac surgical patients, an under-studied yet high-risk population. Non-inferiority of the new fibrinogen concentrate would support its use for patients developing acquired hypofibrinogenemia during cardiac surgery. Results from the FIBRES study are likely to improve care for cardiac surgical patients experiencing significant bleeding. DisclosuresKarkouti:Octapharma US: Research Funding.

When might transferrin, hemopexin or haptoglobin administration be of benefit following the transfusion of red blood cells?

After transfusion, a percentage of red blood cells undergo hemolysis within macrophages. Intravascular exposures to hemin and hemoglobin (Hb) can occur after storage bag hemolysis, some transfusion reactions, during use of medical assist devices and in response to bacterial hemolysins. Proteins that regulate iron, hemin and Hb either become saturated after iron excess (transferrin, Tf) or depleted after hemin (hemopexin, Hpx) and Hb (haptoglobin, Hp) excess. Protein saturation or stoichiometric imbalance created by transfusion increases exposure to non-Tf bound iron, hemin and Hb. Tf, Hpx and Hp are being developed for hematological disorders where iron, hemin and Hb contribute to pathophysiology. However, complexed to their ligands, each represents a potential iron source for pathogens, which may complicate the use of these proteins. Erythrophagocytosis by macrophages and processes of cell death that lead to reactive iron exposure are increasingly described. In addition, the effects of transfusion introduced circulatory hemin and Hb are described in the literature, particularly following large volume transfusion, infection and during concomitant medical device use. Supplementation with Tf, Hpx and Hp suggests therapeutic potential in conditions of extravascular/intravascular hemolysis. However, their administration following transfusion may require careful assessment of concomitant disease.

Improving Outcomes in a Complex Health Care System: Lessons From Complex Cranial Vault Reconstruction.

Reducing blood donor exposure (BDE) is a meaningful improvement goal for many conditions and procedures that require a transfusion of blood products. Complex cranial vault reconstruction (CCVR) in children is a procedure that routinely requires a large-volume blood transfusion, with intraoperative blood loss routinely exceeding the circulating blood volume1–4 and ongoing losses often leading to postoperative transfusions. Large-volume transfusions increase the risk for coagulopathy5 and a need for additional blood products; increasing donor exposure increases the risk for infection, transfusion reactions, and alloimmunization.6 Optimizing the transfusion management for CCVR requires a high degree of care coordination because multiple providers are involved in the care of these children in the preoperative, intraoperative, and postoperative setting.1 In addition, an optimal transfusion strategy for this particular population has not been previously established. In this issue of Hospital Pediatrics , Muhly et al7 report the use of sequential interventions and the evaluation of outcomes over time to achieve an overall goal of reducing BDEs. They also achieve a secondary goal of reducing the overall blood transfusion volume in the CCVR population. Although …

Care Standardization Reduces Blood Donor Exposures and Transfusion in Complex Cranial Vault Reconstruction.

Complex cranial vault reconstruction (CCVR) often requires a large-volume transfusion of blood products. We implemented a series of improvement interventions to reduce blood donor exposures (BDE) and transfusion requirements in CCVR. We implemented interventions over 4 epochs: (E1) reconstituted blood (1:1 ratio of donor-matched red blood cells and fresh-frozen plasma) for intraoperative transfusions, (E2) reconstituted blood plus postoperative transfusion guidelines, (E3) reconstituted blood plus intraoperative antifibrinolytics and postoperative guidelines, and (E4) fresh whole blood for intraoperative transfusion, antifibrinolytics, and postoperative guidelines. Primary outcomes, BDE, and total volume of blood products transfused are presented by using statistical process control charts, with statistical comparisons between each epoch and baseline data. We included 347 patients <72 months old who underwent CCVR between 2008 and 2016 (E1: n = 50; E2: n = 41; E3: n = 87; and E4: n = 169). They were compared with a baseline sample group of 138 patients who were managed between 2001 and 2006. Compared with our baseline group, patients in each epoch had a significant reduction in BDE (P = .02-<.0001). Conversely, compared with the baseline group, we observed an increase the volume of blood products transfused in E1 (P = .004), no difference in E2 (P = .6) or E3 (P = .46), and a reduction in the volume of blood products transfused in E4 (P < .0001). The implementation of sequential clinical improvement strategies resulted in a sustained reduction in BDE whereas only the use of whole blood resulted in a significant reduction in the total volume of blood products transfused in children undergoing CCVR.

The Impact of Blood Transfusion on Recurrence and Mortality Following Colorectal Cancer Resection: A Propensity Score Analysis of 4,030 Patients

Whether blood transfusion exacerbates cancer outcomes after surgery in humans remains inconclusive. We utilized a large cohort to investigate the effect of perioperative blood transfusion on cancer prognosis following colorectal cancer (CRC) resection. Patients with stage I through III CRC undergoing tumour resection at a tertiary medical center between 2005 and 2014 were identified and evaluated through August 2016. Propensity score matching was used to cancel out imbalances in patient characteristics. Postoperative disease-free survival (DFS) and overall survival (OS) were analysed using Cox regression model. A total of 4,030 and 972 patients were analysed before and after propensity score matching. Cox regression analyses demonstrated blood transfusion associated with shorter DFS and OS before and after matching (hazard ratio: 1.41, 95% CI: 1.2–1.66 for DFS; 1.97, 95% CI: 1.6–2.43 for OS). Larger transfusion volume was linked to higher overall mortality (≤4 units vs. nil, HR = 1.58; >4 units vs. nil, HR = 2.32) but not more cancer recurrence. Preoperative anemia was not associated with decreased survival after adjusting covariates. Perioperative blood transfusion was associated with worse cancer prognosis after curative colorectal resection, independently of anemia status. Strategies aimed at minimizing transfusion requirements should be further developed.

Role of heme in lung bacterial infection after trauma hemorrhage and stored red blood cell transfusion: A preclinical experimental study.

BackgroundTrauma is the leading cause of death and disability in patients aged 1–46 y. Severely injured patients experience considerable blood loss and hemorrhagic shock requiring treatment with massive transfusion of red blood cells (RBCs). Preclinical and retrospective human studies in trauma patients have suggested that poorer therapeutic efficacy, increased severity of organ injury, and increased bacterial infection are associated with transfusion of large volumes of stored RBCs, although the mechanisms are not fully understood.Methods and findingsWe developed a murine model of trauma hemorrhage (TH) followed by resuscitation with plasma and leukoreduced RBCs (in a 1:1 ratio) that were banked for 0 (fresh) or 14 (stored) days. Two days later, lungs were infected with Pseudomonas aeruginosa K-strain (PAK). Resuscitation with stored RBCs significantly increased the severity of lung injury caused by P. aeruginosa, as demonstrated by higher mortality (median survival 35 h for fresh RBC group and 8 h for stored RBC group; p < 0.001), increased pulmonary edema (mean [95% CI] 106.4 μl [88.5–124.3] for fresh RBCs and 192.5 μl [140.9–244.0] for stored RBCs; p = 0.003), and higher bacterial numbers in the lung (mean [95% CI] 1.2 × 107 [−1.0 × 107 to 2.5 × 107] for fresh RBCs and 3.6 × 107 [2.5 × 107 to 4.7 × 107] for stored RBCs; p = 0.014). The mechanism underlying this increased infection susceptibility and severity was free-heme-dependent, as recombinant hemopexin or pharmacological inhibition or genetic deletion of toll-like receptor 4 (TLR4) during TH and resuscitation completely prevented P. aeruginosa–induced mortality after stored RBC transfusion (p < 0.001 for all groups relative to stored RBC group). Evidence from studies transfusing fresh and stored RBCs mixed with stored and fresh RBC supernatants, respectively, indicated that heme arising both during storage and from RBC hemolysis post-resuscitation plays a role in increased mortality after PAK (p < 0.001). Heme also increased endothelial permeability and inhibited macrophage-dependent phagocytosis in cultured cells. Stored RBCs also increased circulating high mobility group box 1 (HMGB1; mean [95% CI] 15.4 ng/ml [6.7–24.0] for fresh RBCs and 50.3 ng/ml [12.3–88.2] for stored RBCs), and anti-HMGB1 blocking antibody protected against PAK-induced mortality in vivo (p = 0.001) and restored macrophage-dependent phagocytosis of P. aeruginosa in vitro. Finally, we showed that TH patients, admitted to the University of Alabama at Birmingham ER between 1 January 2015 and 30 April 2016 (n = 50), received high micromolar–millimolar levels of heme proportional to the number of units transfused, sufficient to overwhelm endogenous hemopexin levels early after TH and resuscitation. Limitations of the study include lack of assessment of temporal changes in different products of hemolysis after resuscitation and the small sample size precluding testing of associations between heme levels and adverse outcomes in resuscitated TH patients.ConclusionsWe provide evidence that large volume resuscitation with stored blood, compared to fresh blood, in mice increases mortality from subsequent pneumonia, which occurs via mechanisms sensitive to hemopexin and TLR4 and HMGB1 inhibition.

Initiation and Termination of Massive Transfusion Protocols: Current Strategies and Future Prospects.

The advent of massive transfusion protocols (MTP) has had a significant positive impact on hemorrhaging trauma patient morbidity and mortality. Nevertheless, societal MTP guidelines and individual MTPs at academic institutions continue to circulate opposing recommendations on topics critical to MTPs. This narrative review discusses up-to-date information on 2 such topics, the initiation and termination of an MTP. The discussion for each begins with a review of the recommendations and supporting literature presented by MTP guidelines from 3 prominent societies, the American Society of Anesthesiologists, the American College of Surgeons, and the task force for Advanced Bleeding Care in Trauma. This is followed by an in-depth analysis of the main components within those recommendations. Societal recommendations on MTP initiation in hemorrhaging trauma patients emphasize the use of retrospectively validated massive transfusion (MT) prediction score, specifically, the Assessment of Blood Consumption and Trauma-Associated Severe Hemorrhage scores. Validation studies have shown that both scoring systems perform similarly. Both scores reliably identify patients that will not require an MT, while simultaneously overpredicting MT requirements. However, each scoring system has its unique advantages and disadvantages, and this review discusses how specific aspects of each scoring system can affect widespread applicability and statistical performance. In addition, we discuss the often overlooked topic of initiating MT in nontrauma patients and the specific tools physicians have to guide the MT initiation decision in this unique setting. Despite the serious complications that can arise with transfusion of large volumes of blood products, there is considerably less research pertinent to the topic of MTP termination. Societal recommendations on MTP termination emphasize applying clinical reasoning to identify patients who have bleeding source control and are adequately resuscitated. This review, however, focuses primarily on the recommendations presented by the Advanced Bleeding Care in Trauma's MTP guidelines that call for prompt termination of the algorithm-guided model of resuscitation and rapidly transitioning into a resuscitation model guided by laboratory test results. We also discuss the evidence in support of laboratory result-guided resuscitation and how recent literature on viscoelastic hemostatic assays, although limited, highlights the potential to achieve additional benefits from this method of resuscitation.

The Clinical Efficacy of Fibrinogen Concentrate in Massive Obstetric Haemorrhage with Hypofibrinogenaemia

Massive obstetric haemorrhage remains a major cause of maternal death attributable to hypofibrinogenaemia. Transfusion of large volumes of fresh frozen plasma (FFP) is required to normalise fibrinogen levels. We compared the efficacy of FFP (F group) with that of FFP plus fibrinogen concentrate (F + F group) in massive obstetric haemorrhage. In this retrospective study, we compared the medical charts (2004–2016) of 137 patients with <150 mg/dl fibrinogen treated with F + F (n = 47; after August 2009) or F (n = 56; before August 2009). Although fibrinogen concentrate was only administered in severe cases, the FFP/red blood cell concentrate (RCC) ratio was significantly lower in the F + F group than in the F group. A sub-group analysis of cases requiring ≥18 RCC units showed that the F + F group received significantly less FFP than the F group (40.2 ± 19.6 versus 53.4 ± 18.5 units; P = 0.047) and showed significantly less pulmonary oedema (24.0% vs 57.1%; P < 0.05) in the absence of any significant differences in pre-transfusion coagulation, estimated blood loss, or RCC transfusion volume. Administration of fibrinogen concentrate increased the rate of fibrinogen supplementation five-fold and reduced FFP dosage, the FFP/RCC ratio, and the incidence of pulmonary oedema.

Perioperative Outcomes and Management in Pediatric Complex Cranial Vault Reconstruction: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.

The Pediatric Craniofacial Collaborative Group established the Pediatric Craniofacial Surgery Perioperative Registry to elucidate practices and outcomes in children with craniosynostosis undergoing complex cranial vault reconstruction and inform quality improvement efforts. The aim of this study is to determine perioperative management, outcomes, and complications in children undergoing complex cranial vault reconstruction across North America and to delineate salient features of current practices. Thirty-one institutions contributed data from June 2012 to September 2015. Data extracted included demographics, perioperative management, length of stay, laboratory results, and blood management techniques employed. Complications and outlier events were described. Outcomes analyzed included total blood donor exposures, intraoperative and perioperative transfusion volumes, and length of stay outcomes. One thousand two hundred twenty-three cases were analyzed: 935 children aged less than or equal to 24 months and 288 children aged more than 24 months. Ninety-five percent of children aged less than or equal to 24 months and 79% of children aged more than 24 months received at least one transfusion. There were no deaths. Notable complications included cardiac arrest, postoperative seizures, unplanned postoperative mechanical ventilation, large-volume transfusion, and unplanned second surgeries. Utilization of blood conservation techniques was highly variable. The authors present a comprehensive description of perioperative management, outcomes, and complications from a large group of North American children undergoing complex cranial vault reconstruction. Transfusion remains the rule for the vast majority of patients. The occurrence of numerous significant complications together with large variability in perioperative management and outcomes suggest targets for improvement.

Efficacy and Safety of Prothrombin Complex Concentrate in Patients Undergoing Major Cardiac Surgery

IntroductionAdministration of coagulation factors after major cardiac surgery, with or without cardiopulmonary bypass, may be a strategy for reducing risk of bleeding and requirement for allogeneic blood transfusions. However, transfusion of large volumes of fresh frozen plasma (FFP) is restricted by the competing problem of heart failure, a common complication following cardiac surgery in patients with existing cardiac decompensation. Prothrombin complex concentrate (PCC) has a smaller volume of administration than FFP for a similar amount of coagulation factors, making it an attractive option in this situation. However, patients undergoing complex cardiac surgery may also have prothrombotic conditions and have a high risk of both venous and arterial thrombosis including ischemic neurological complications. We performed a retrospective analysis to investigate whether the use of PCC is safe and effective compared with FFP to treat coagulopathy in patients undergoing isolated coronary artery bypass graft (CABG), valve surgery (with or without concomitant CABG) and major aortic procedures. If the patient was on warfarin, this was stopped at least 5 days before the surgery and appropriate bridging was followed. For patients on dual antiplatelet therapy, P2Y12 receptor inhibitors such as Clopidogrel and Prasugrel were stopped 5-7days before the surgery and Aspirin was allowed to continue. The decision to use PPC or FFP was based on individual patient characteristics such as complexity of the surgery and previous history of increased bleeding during surgery and also ability to tolerate volume.MethodsOne hundred and seventy consecutive adult patients who underwent major cardiac surgery between January 2015 and December 2015 were studied. Among them, 87 received PCC (male/female = 55/32, mean age= 56 years) and 83 received FFP (male/female = 56/27, mean age = 58 years) to control coagulopathy. The decision on need for coagulation factor treatment and the choice of treatment was made by the treating team of the patient. Those who received both PCC and FFP were excluded. Blood loss within first 12 hours and 24hours from the end of operation, total use of allogeneic blood and platelet transfusion and patient outcomes in terms of thrombotic complications both venous and arterial, incidence of acute kidney injury and 30 day mortality were compared in the two groups. Antiplatelet drug effect on bleeding was also assessed.ResultsThere was no significant difference in the amount of bleeding at the first 12 hours from the end of the operation in the two groups (p=0.25) :median and 95% confidence interval [CI] were 825mL [926-1317] and 787mL [804-1067] patients received PPC or FFP respectively. However, total blood loss within 24hours was significantly higher in patients who received PPC (median [CI] (1575mL [1658-2263]) compared to FFP (median [CI] (1213mL [1244-1641]), P=0.0034. There was no difference in the mean blood loss between patients continued Aspirin at the time of surgery and those who were not on Aspirin in either groups. The use of allogeneic blood (P=.001) and platelets (P=0.03) was significantly higher in patients receiving FFP compared to PPC. A significantly higher number of patients treated with FFP (9.6% vs 3.5%, p=0.002) developed cardiac failure related to circulatory overload. There was no difference in thrombotic events in the two groups: one patient from each group (1.1%) developed venous and arterial thrombosis respectively following surgery. Thirty day mortality rate was similar in the patients receiving FFP or PPC (4%) and none were directly related to surgery. There was no difference in the acute kidney injury in the two groups.ConclusionsThis retrospective analysis suggests that PCC may be an alternative to FFP in patients undergoing major cardiac surgery. Although there was a higher amount of bleeding within 24hours of surgery in patients treated with PCC, this may reflect the complexity, duration and the individual patient risk of bleeding due to selection bias. The use of PPC may reduce the number of allogeneic blood and platelet transfusion in these patients and reduce risk of circulatory overload. There was no increased risk of thrombosis with use of PCC. However, randomized controlled studies powered to evaluate efficacy and safety in patients receiving PCC versus FFP for coagulopathic bleeding after major cardiac surgery are warranted. DisclosuresLaffan:CSL: Other: Travel support; Octapharma: Speakers Bureau.

Guidelines on transfusion for fetuses, neonates and older children.

Guidelines on transfusion for fetuses, neonates and older children.

Functional characterization of novel ABCB6 mutations and their clinical implications in familial pseudohyperkalemia.

Isolated familial pseudohyperkalemia is a dominant red cell trait characterized by cold-induced 'passive leak' of red cell potassium ions into plasma. The causative gene of this condition is ABCB6, which encodes an erythrocyte membrane ABC transporter protein bearing the Langereis blood group antigen system. In this study analyzing three new families, we report the first functional characterization of ABCB6 mutants, including the homozygous mutation V454A, heterozygous mutation R276W, and compound heterozygous mutations R276W and R723Q (in trans). All these mutations are annotated in public databases, suggesting that familial pseudohyperkalemia could be common in the general population. Indeed, we identified variant R276W in one of 327 random blood donors (0.3%). Four weeks' storage of heterozygous R276W blood cells resulted in massive loss of potassium compared to that from healthy control red blood cells. Moreover, measurement of cation flux demonstrated greater loss of potassium or rubidium ions from HEK-293 cells expressing ABCB6 mutants than from cells expressing wild-type ABCB6. The R276W/R723Q mutations elicited greater cellular potassium ion efflux than did the other mutants tested. In conclusion, ABCB6 missense mutations in red blood cells from subjects with familial pseudohyperkalemia show elevated potassium ion efflux. The prevalence of such individuals in the blood donor population is moderate. The fact that storage of blood from these subjects leads to significantly increased levels of potassium in the plasma could have serious clinical implications for neonates and infants receiving large-volume transfusions of whole blood. Genetic tests for familial pseudohyperkalemia could be added to blood donor pre-screening. Further study of ABCB6 function and trafficking could be informative for the study of other pathologies of red blood cell hydration.

Efficacy and feasibility of ambulatory treatment-based monthly nedaplatin plus S-1 in definitive or salvage concurrent chemoradiotherapy for early, advanced, and relapsed esophageal cancer.

BackgroundStandard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution.MethodsPatients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m2 was given on days 1 and 29, and S-1 80 mg/m2 on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks.ResultsBetween August 2011 and June 2015, 89 patients (age range, 44–86 years; K-PS 90–100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients.ConclusionsNedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT.

Consumptive Coagulopathy after Commencement of Continuous Renal-Replacement Therapy in Patients with Decompensated Cirrhosis: A Case Series

Over a four-month period, three patients with ascites and hyponatraemia secondary to decompensated cirrhosis were admitted to the Intensive Care unit (ICU) of a quaternary referral centre for liver disease and transplantation for further management. Each had a stable documented coagulopathy without bleeding on ICU admission. Following commencement of anticoagulant-free continuous renal replacement therapy (CRRT), a severe bleeding diathesis developed in all three patients necessitating transfusion of large volumes of blood products. The clinical presentation and results of detailed coagulation profiles and thromboelastography (TEG) were consistent with the development of disseminated intravascular coagulation (DIC) with hyperfibrinolysis. The onset of DIC in all three cases was associated with significant morbidity. One patient went on to receive an orthotopic liver transplant (OLT) and death was the end result in the subsequent two cases. Due to the temporal relationship, we hypothesise that the initiation of CRRT may have contributed to the derangement in coagulation status in these patients. Though the exact mechanism is uncertain, it may be related to a higher rate of adsorption of high molecular weight kinins or the CRRT membrane’s ability to bind endogenous heparinoids. These cases highlight the precarious nature of the coagulation cascade in patients with decompensated cirrhosis. Initiation of CRRT may profoundly disrupt that tenuous balance and should be preceded by careful consideration of the potential complications including DIC and its associated morbidity.