Blood Infusion Research Articles

Human Umbilical Cord Blood Infusions in the Management of Autism Spectrum Disorder.

Objective: To provide an overview of the role of umbilical cord blood (UCB) in managing autism spectrum disorder (ASD) symptoms in children aged 4-8 years.Data Sources: A systematic literature search was conducted using the terms (autism OR autism spectrum disorder AND umbilical cord blood infusion UCB OR umbilical cord blood). The review was limited to articles published in the English language from 1945 to September 2020. The database search included PubMed, Scopus, and EMBASE.Study Selection: The initial search revealed 165 hits of potential relevance.Data Extraction: The articles were analyzed to obtain clinical information relevant to meeting the review objectives.Data Synthesis: After title, abstract, and full article review, 3 UCB studies were selected for analysis.Results: The systematic review showed mixed results. In the first study, improvements were seen in the socialization and communication domains and adaptive behavior with UCB infusion. The Pervasive Developmental Disorder Behavior Inventory composite T score and Expressive One-Word Picture Vocabulary Test (EOWPVT) score also improved. Symptomatic improvement was seen in half of the patients. The second study showed no improvement in the EOWPVT, Receptive One-Word Picture Vocabulary Test, Clinical Global Impressions scale, or Vineland Adaptive Behavior Scales (VABS), second edition. The third study showed nonsignificant improvement in the VABS, third edition socialization scale scores; however, major improvement in the communication domain was seen for those with nonverbal IQ ≥ 70. No serious adverse events were reported in any of the studies.Conclusion: Few studies have evaluated the role of UCB infusion in addressing symptoms of ASD. Due to the limited number of studies, more research is warranted.

Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death-induced Lung Injury in Pigs.

Rationale: Donor brain death-induced lung injury may compromise graft function after transplantation. Establishing strategies to attenuate lung damage remains a challenge because the underlying mechanisms remain uncertain. Objectives: The effects of tacrolimus pretreatment were evaluated in an experimental model of brain death-induced lung injury. Methods: Brain death was induced by slow intracranial infusion of blood in anesthetized pigs after randomization to tacrolimus (orally administered at 0.25 mg ⋅ kg-1 twice daily the day before the experiment and intravenously at 0.05 mg ⋅ kg-1 1 h before the experiment; n = 8) or placebo (n = 9) pretreatment. Hemodynamic measurements were performed 1, 3, 5, and 7 hours after brain death. After euthanasia of the animals, lung tissue was sampled for pathobiological and histological analysis, including lung injury score (LIS). Measurements and Main Results: Tacrolimus pretreatment prevented increases in pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary pressure and decreases in systemic arterial pressure and thermodilution cardiac output associated with brain death. After brain death, the ratio of PaO2 to FiO2 decreased, which was prevented by tacrolimus. Tacrolimus pretreatment prevented increases in the ratio of IL-6 to IL-10, VCAM1 (vascular cell adhesion molecule 1), circulating concentrations of IL-1β, and glycocalyx-derived molecules. Tacrolimus partially decreased apoptosis (Bax [Bcl2-associated X apoptosis regulator]-to-Bcl2 [B-cell lymphoma-2] ratio [P = 0.07] and number of apoptotic cells in the lungs [P < 0.05]) but failed to improve LIS. Conclusions: Immunomodulation through tacrolimus pretreatment prevented pulmonary capillary hypertension as well as the activation of inflammatory and apoptotic processes in the lungs after brain death; however, LIS did not improve.

A comparison of the content taught in critical care transportation modules across South African bachelor's degrees in emergency medical care.

Background and objective Critical care transport (CCT) involves the movement of critically ill patients between healthcare facilities. South Africa (SA), like other low- to middle-income countries, has a relative shortage of ICU beds, making CCT an inevitability. In SA, CCTs are mostly done by emergency care practitioners; however, it is unclear how universities offering Bachelor in Emergency Medical Care (BEMC) courses approach their teaching in critical care and whether the content taught is consistent between institutions. In our study we formally evaluate and compare the intensive and critical care transport modules offered at SA universities in their BEMC programmes. Methods The electronic version of curricula of the critical care transport modules from higher education institutes in SA offering the BEMC were subjected to document analysis. Qualitative (inductive content analysis) and quantitative (descriptive analysis) methods were used to describe and compare the different components of the curriculum. Curricula were assigned into components and sub-components according to accepted definitions of curricula. The components included: aims, goals, composition and objectives of the course; content or teaching material and work-integrated learning. Results The four universities that offer BEMC programmes were invited to participate, and three (75%) consented and provided data. The duration of the modules ranged from 6 to 12 months, corresponding with notional hours of 120 - 150. A total of 83 learning domains were generated from the coding process. These domains included content on mechanical ventilation, patient monitoring, arterial blood gases, infusions and fluid balance, and patient preparation and transfer. Two universities had identical structures and learning outcomes, while one had a different structure and outcomes; it corresponded with a 58% similarity. Clinical placements were in critical and emergency care units, operating theatres and prehospital clinical services. Conclusion In all components compared, the universities offering BEMC were more similar than they were different. It is unclear whether the components taught are relevant to the SA patient population and healthcare system context, or whether students are adequately prepared for clinical practice. Postgraduate educational programmes might need to be developed to equip emergency care practitioners to function in this environment safely. Contributions of the study Owing to the limited availability of ICU beds in South Africa, optimising and standardising critical care transport is an important consideration. This study identifies important elements for improving emergency medical care training in South Africa, as well as areas needing further research.

Performance comparison of intraosseous devices and setups for infusion of whole blood in a cadaveric swine bone model.

Intraosseous (IO) access can provide a critical bridge for blood product infusion when peripheral venous access is not obtainable. Successful pressurized IO infusion requires flow rates sufficient to preserve life, but with infusion pressures low enough to avoid clinical complications (e.g., hemolysis, bone damage, fat emboli). However, the optimal method for pressured IO delivery of blood was unknown. Three trained physicians infused 500 mL of whole blood through a 15-gauge, 45 mm IO catheter into fresh, high bone density cadaveric swine proximal humeri. Participants applied eight different pressure infusion strategies: (1) gravity, (2) pressure bag, (3) pressure bag actively maintained at or above 300 mmHg, (4) hand pump, (5) hand pump with pressure bag, (6) push-pull with 10 mL syringe, (7) push-pull with 60 mL syringe, and a (8) Manual Rapid Infuser in a randomized within-subjects design (30 trials per method, 240 trials total). The primary outcomes of flow rates, mean and peak pressures, and user ratings were contrasted using ANOVA at p < 0.05. The Manual Rapid Infuser conferred the highest flow rates (199 ± 3 mL/min) and most favorable user ratings, but also the highest mean and peak pressures. Push-pull conferred the next highest flow rates (67 ± 5 mL/min for 60 mL, 56 ± 2 mL/min for 10 mL) and pressures, with intermediate-to-high user ratings. Hand pump flow rates were essentially identical with (45 ± 4 mL/min) or without (44 ± 3 mL/min) pressure bag, with high user ratings without a pressure bag. Pressure bag and gravity methods conferred low flow rates and user ratings. Some pressured IO infusion methods can achieve flow rates adequate to serve as a resuscitative bridge in the massively hemorrhaged trauma victim, but flow rates and pressures vary greatly across IO pressurized infusion methods. Manual Rapid Infuser and push-pull methods conferred high flow rates but also relatively high pressures, highlighting the importance of using in vivo models in future research to assess the possible clinical complications of using these promising methods. Combined, present findings highlight the importance of studying pressurized IO methods towards preserving the life of the critically injured trauma victim.

Effects of Tacrolimus on Mechanical and Humoral Determinants of Brain Death-Induced Lung Injury

<h3>Purpose</h3> Donor brain death-induced lung injury may compromise graft function after transplantation. The mechanisms of this particular form of neurogenic lung edema and its possible prevention by immunomodulator Tacrolimus remain incompletely understood. <h3>Methods</h3> Brain death was induced, by slow intracranial infusion of blood, in anesthetized pigs after randomisation to placebo (n=9) or to Tacrolimus (n=8). One, three, five and seven hours after brain death, pulmonary artery pressure (Pap), wedged Pap (Papo), right atrial pressure (Pra), effective pulmonary capillary pressure (Pcap), systemic artery pressure (Psa) and thermodilution cardiac output (Q) were measured. Blood and lung tissue were sampled and lung injury scored on pathological examination. <h3>Results</h3> Brain death was associated with marked increases in Pap, PVR and Pcap, decreases in Psa and Q with growing need for Noradrenaline while Ppao and Pra remained in a physiological range. Arterial O₂ pressure to fraction of inspired O₂(PaO₂/FiO₂) decreased. Brain death was associated with increased lung injury score together with increased gene expressions of interleukin (IL)-6 and IL-1βετα, heme-oxygenase-1, signal transducer and activator of transcription-3. Lung tissue pro-inflammatory IL-6/IL-10 ratio was decreased and pro-apoptotic Bax/Bcl2 ratio was increased. Tacrolimus partially corrected pulmonary hypertension and lung tissue biological perturbations. PaO₂/FiO₂ was inversely correlated to PCP and lung injury score. Serum IL-6 and IL-1βετα were correlated to PCP. <h3>Conclusion</h3> Brain death induced lung injury is related to effective pulmonary capillary hypertension with normal PAWP and pro-inflammatory and pro-apoptotic biological changes all partially reversed by preventive Tacrolimus treatment.

Effect of Hypoxic Blood Infusion on Pulmonary Physiology.

The ability to store red blood cells (RBCs) and other components for extended periods of time has expanded the availability and use of transfusion as a life-saving therapy. However, conventional RBC storage has a limited window of effective preservation and is accompanied by the progressive accumulation of a series of biochemical and morphological modifications, collectively referred to as “storage lesions.” These lesions have been associated with negative clinical outcomes (i.e., postoperative complications as well as reduced short-term and long-term survival) in patients transfused with conventionally stored blood with older and deteriorated transfused red cells. Hence, there is an increased unmet need for improved RBC storage. Hypoxic storage of blood entails the removal of large amounts of oxygen to low levels prior to refrigeration and maintenance of hypoxic levels through the entirety of storage. As opposed to conventionally stored blood, hypoxic storage can lead to a reduction of oxidative damage to slow storage lesion development and create a storage condition expected to result in enhanced efficacy of stored RBCs without an effect on oxygen exchange in the lung. Hypoxic blood transfusions appear to offer minimal safety concerns, even in patients with hypoxemia. This review describes the physiology of hypoxically stored blood, how it differs from conventionally stored blood, and its use in potential clinical application, such as massively transfused and critically ill patients with oxygenation/ventilation impairments.

Single-cell analysis by mass cytometry reveals CD19 CAR T cell spatiotemporal plasticity in patients

ABSTRACT The adaptive T cell immune response requires cellular plasticity to generate distinct subsets with diverse functional and migratory capacities. Studies of CAR T cells have primarily focused on a limited number of phenotypic markers in blood, representing an incomplete view of CAR T cell complexity. Here, we adapted mass cytometry to simultaneously analyze trafficking and functional proteins expression in CD19 CAR T cells across patients’ tissues, including leukapheresis T cells, CAR product, CAR T cells in peripheral blood, bone marrow, and cerebrospinal fluid post infusion and correlate them with phenotypes. This approach revealed spatiotemporal plasticity of CAR T cells. Patients’ CAR product revealed upregulation in many trafficking and activation molecules compared to leukapheresis T cells as baseline. Including statistically significant upregulation in CD4 and CD8 integrin-β7, CD4 granzyme B, and CD11a as well as CD8 CD25 and CD95. Moreover, patients’ tissues showed spatiotemporal alteration in trafficking, activation, maturation, and exhaustion features, with a distinct signature in the central nervous system niche. Compared to peripheral blood samples, cerebrospinal fluid samples were statistically significant enriched in CD4 and CD8 trafficking and memory phenotype proteins integrin β7, CCR7, CXCR4, and CD8 CD69. Our data provide a potential framework to remodel CAR T cells and enhance immunotherapy efficacy.

The rate of decline in fetal hemoglobin following intrauterine blood transfusion in the management of red cell alloimmunization

ObjectiveHemolytic disease of the fetus and newborn is characterized by fetal anemia, secondary to maternal alloantibody-mediated fetal erythrocyte destruction. Despite our reliance on intrauterine blood transfusion (IUT) to maintain severely affected pregnancies, it remains difficult to predict the fetal response to an infusion of donor blood. Our objective was to determine the daily rate of decline in fetal hemoglobin following one, two, and three transfusions. We also evaluated the relationship between the fetal hemoglobin level and the corresponding doppler measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV). Study DesignA prospective observational study of all singleton pregnancies treated with intrauterine transfusion for fetal anemia secondary to maternal alloimmunization at the National Maternity Hospital, a tertiary referral centre, was conducted over a 10-year period (2011–2020). Demographic and clinical data was obtained from the electronic patient records. Ethical approval was granted by the Ethics and Research Committee of the National Maternity Hospital. ResultsA total of 90 intrauterine blood transfusions were performed in 41 fetuses affected by maternal alloimmunization, of which 70% (n = 29), 34% (n = 14) and 15% (n = 6) required a 2nd, 3rd, and 4th transfusion, respectively. The mean rate of decline in fetal hemoglobin following the first transfusion was 0.4 g/dl/day (range, 0.12–0.64 g/dl/day). The mean rate of decline was lower after repeat transfusions at 0.27 g/dl/day (range, 0.16–0.45 g/dl/day). The sensitivity of MCA-PSV threshold of 1.5 Multiples of the Median (MoM) to detect moderate-severe anaemia declined with rank of IUT, from 82% after one previous transfusion, to 75% after two or more previous transfusions. No fetal mortality was seen in our series. ConclusionKnowledge of the expected rate of decline in fetal hemoglobin following an IUT aids in the determination of appropriate timing of subsequent transfusions in a fetus affected by red cell alloimmunization. We observed a reducing rate of daily decline in hemoglobin in fetuses requiring successive transfusions. Our findings suggest a reduced accuracy of the MCA-PSV threshold of 1.5 MoM in determining the optimal timing of 2nd, 3rd, and 4th transfusions.

Preliminary discussion on the prevention and treatment of shock after severe burns

Shock is one of the most common complications and one of the main causes of death after severe burns. The prevention and treatment of shock runs through the whole process of severe burn treatment. Shocks after severe burns, based on their causes, are mainly classified as follows: hypovolemic shock characterized by elevated hematocrit, also known as burn shock, and caused by serious leakage of intravascular fluid to body surface and interstitial spaces in the early stage of burns; hemorrhagic shock caused by large scale of incision and tension reduction, gastrointestinal stress ulcer, or large area of escharectomy and tangential excision surgery; septic shock caused by various microbial invasion; anaphylactic shock caused by infusion of drugs or blood. From the perspective of the reduction of effective circulating volume, burn shock and hemorrhagic shock are hypovolemic shocks, and septic shock and anaphylactic shock are vasodilatory shocks. As the aforementioned shocks vary in terms of occurrence timing, occurrence mechanism, and clinical manifestations, individualized strategies should be adopted for the prevention and treatment.

P-L03 The efficacy and safety of controlled low central venous pressure for liver resection: a systematic review and meta-analysis

Abstract Background Partial hepatectomy is an effective treatment for benign and malignant liver diseases . However, intraoperative bleeding is one of the major factors affecting the outcome of hepatectomy. Currently, the most commonly used method of hepatic blood flow occlusion in clinical practice is Pringle method, but this method has a great impact on liver function and can cause hepatic ischemia-reperfusion injury. .Studies have shown that blood loss volume during hepatectomy is related to central venous pressure (CVP) . Intraoperative control of central venous pressure (LCVP) is increasingly popular in hepatectomy, but its effectiveness and safety remain controversial. Methods The main result of the analysis was to reduce the blood loss and blood infusion. Secondary outcomes included operative time, fluid infusion, urine volume, ALT, TBIL, BUN, CR, postoperative complication rates and length of hospital stay. Statistical analysis was performed using RevMan 5.3 software (Cochrane Collaboration, Oxford, England). The results of all studies were measured by mean ± standard deviation. If there is significant heterogeneity between the results (P &amp;lt; 0.05), a random-effects model is used. A fixed-effect model was used when there was no significant heterogeneity (P &amp;gt; 0.05). Heterogeneity was assessed using the Cochrane χ2 text . Results In total, 10 studies, involving 324 patients undergoing liver resection with controlled low central venous pressure, were identified. Meta-analysis showed that blood loss in the LCVP group was significantly less than that in the control group ( P = 0.0002). blood transfusion in the LCVP group was also significantly less than that in the control group(P = 0.0006). there was no difference between LCVP group and control group in operation time(P = 0.17), fluid infusion( P = 0.46), urinary volume(P = 0.38), ALT( P = 0.23), TBIL(P = 0.86), BUN(P = 0.67), CR(P =0.59), postoperative complication rates( P = 0.01) and hospital stay(P = 0.26). Conclusions Compared with the control, controlled low central venous pressure showed comparable efficacy and safety for the treatment during liver resection.

Granulocyte colony-stimulating factor protected against brain injury in a rat cerebral hemorrhage model by modulating inflammation.

Granulocyte colony-stimulating factor (G-CSF) has been reported to exert a protective effect against secondary brain damage, but the underlying mechanisms remain unknown. We explored the ability of G-CSF to protect the brain from injury in a rat autologous blood-induced model of intracerebral hemorrhage (ICH), with a special focus on the anti-inflammation effect. An ICH was induced in 8-week-old male rats by an infusion of autologous blood, and the rats were then randomly assigned to five treatment groups: sham, ICH, and ICH+ low-dose (25 µg/kg), middle-dose (50 µg/kg), and high-dose (75 µg/kg) G-CSF. We then evaluated the levels of brain inflammation-related genes and proteins. The levels of tumor-necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) mRNA increased between days 1 and 14 post-ICH, with the highest expression on day 3. These changes were rectified by G-CSF in a dose-dependent manner. At day 3 post-injury, an elevation of the nuclear factor-kappa B (NF-κB) p65 protein level and a reduction of the inhibitor of NF-κB alpha (IκBα) protein level were observed; G-CSF treatment exerted a beneficial effect on both protein expressions. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were increased; these changes were rectified by the highest dose of G-CSF. The brain-protecting effects of G-CSF are likely to be attributable, at least in part, to attenuation of the TNF-α, IL-6, iNOS, and COX-2 expressions induced by NF-κB activation in the brain tissues of this autologous blood-induced ICH rat model.

Stem Cell and Macrophage Roles in Skeletal Muscle Regenerative Medicine.

In severe muscle injury, skeletal muscle tissue structure and functionality can be repaired through the involvement of several cell types, such as muscle stem cells, and innate immune responses. However, the exact mechanisms behind muscle tissue regeneration, homeostasis, and plasticity are still under investigation, and the discovery of pathways and cell types involved in muscle repair can open the way for novel therapeutic approaches, such as cell-based therapies involving stem cells and peripheral blood mononucleate cells. Indeed, peripheral cell infusions are a new therapy for muscle healing, likely because autologous peripheral blood infusion at the site of injury might enhance innate immune responses, especially those driven by macrophages. In this review, we summarize current knowledge on functions of stem cells and macrophages in skeletal muscle repairs and their roles as components of a promising cell-based therapies for muscle repair and regeneration.

Expanded Access Protocol of Umbilical Cord Blood Infusion for Children with Neurological Conditions: An Update.

Expanded Access Protocol of Umbilical Cord Blood Infusion for Children with Neurological Conditions: An Update.

Profiling of Blood-Brain Barrier Disruption in Mouse Intracerebral Hemorrhage Models: Collagenase Injection vs. Autologous Arterial Whole Blood Infusion.

Disruption of the blood-brain barrier (BBB) and the subsequent formation of brain edema is the most severe consequence of intracerebral hemorrhage (ICH), leading to drastic neuroinflammatory responses and neuronal cell death. A better understanding of ICH pathophysiology to develop effective therapy relies on selecting appropriate animal models. The collagenase injection ICH model and the autologous arterial whole blood infusion ICH model have been developed to investigate the pathophysiology of ICH. However, it remains unclear whether the temporal progression and the underlying mechanism of BBB breakdown are similar between these two ICH models. In this study, we aimed to determine the progression and the mechanism of BBB disruption via the two commonly used murine ICH models: the collagenase-induced ICH model (c-ICH) and the double autologous whole blood ICH model (b-ICH). Intrastriatal injection of 0.05 U collagenase or 20 μL autologous blood was used for a comparable hematoma volume in these two ICH models. Then we analyzed BBB permeability using Evan’s blue and IgG extravasation, evaluated tight junction (TJ) damage by transmission electron microscope (TEM) and Western blotting, and assessed matrix metalloproteinase-9 (MMP-9) activity and aquaporin 4 (AQP4) mRNA expression by Gelatin gel zymography and RT-PCR, respectively. The results showed that the BBB leakage was associated with a decrease in TJ protein expression and an increase in MMP-9 activity and AQP4 expression on day 3 in the c-ICH model compared with that on day 5 in the b-ICH model. Additionally, using TEM, we found that the TJ was markedly damaged on day 3 in the c-ICH model compared with that on day 5 in the b-ICH model. In conclusion, the BBB was disrupted in the two ICH models; compared to the b-ICH model, the c-ICH model presented with a more pronounced disruption of BBB at earlier time points, suggesting that the c-ICH model might be a more suitable model for studying early BBB damage and protection after ICH.

Risk factors for surgical site infection and association of surgical site infection with survival of lower rectal cancer patients without clinical lateral pelvic lymph node metastasis (clinical Stage II/III): Analysis of data from JCOG0212

This study aimed to examine the risk factors for surgical site infection (SSI) and the association of that with recurrence in JCOG0212. The results for secondary endpoints showed that compared with the mesorectal excision (ME) alone group, ME with lateral lymph node dissection (LLND) group showed significantly longer operative time and significantly higher blood loss. These results suggested that LLND was a risk factor for SSI. All 701 patients registered in JCOG0212 were analyzed in this study. Wound infection was defined as incisional/deep SSI, and pelvic abscess and anastomotic leakage were defined as organ/space SSI. The risk factors for the incidence of SSI and the effect of SSI on relapse-free survival (RFS) were investigated. Multivariable odds ratio of Grade 2 or higher all SSI was 0.58 [95% Confidence interval: 0.36–0.93] for female (vs. male) and that of Grade 2 or higher incisional/deep SSI was 2.24 [1.03–4.86] for blood infusion. For RFS, patients with Grade 3 or higher all SSI showed poor prognosis (multivariable hazard ratio: 1.66 [1.03–2.68]). LLND is not significant factor for the incidence of all SSI. Male sex might be a risk factor of Grade 2 or higher SSI, and blood transfusion is a possible risk factor of Grade 2 or higher incisional/deep SSI. Grade 3 or higher all SSI might be a significant worse prognostic factor for lower rectal cancer.

The characteristics and influencing factors of fever in postoperative patients undergoing percutaneous nephrolithotomy: A retrospective analysis.

Percutaneous nephrolithotomy (PCNL) is commonly used for the treatment of upper urinary calculi in clinical setting, and fever is a common complication after PCNL. It is necessary to evaluate the risk factors of fever in patients undergoing PCNL, to provide insights into the management of PCNL.Patients who underwent PCNL in our hospital from January 2018 to August 2020 were included. The clinical data of postoperative fever and no fever patients were collected and assessed. Logistic regression analyses were conducted to analyze the risk factors for fever in patients undergoing PCNL.A total of 276 patients undergoing PCNL were included, the incidence of postoperative fever for patients undergoing PCNL was 19.39%. No significant differences in the gender, body mass index, alcohol drinking, smoking, hypertension, hyperlipidemia, intraoperative blood infusion, length of hospital stay between fever patients, and no fever patients were found (all P > .05). There were significant differences in the age, diabetes, size of stones, duration of surgery between fever patients, and no fever patients (all P < .05). Age ≥60 years (odds ratio [OR] 2.143, 95% confidence interval [CI] 1.101∼3.264), diabetes (OR 2.218, 95% CI 1.176∼4.642), size of stone ≥2 cm (OR 1.428, 95%CI 1.104∼2.055), duration of surgery ≥100 minutes (OR 1.334, 95% CI 1.015∼1.923) were the risk factors for fever in patients with PCNL (all P < .05). Escherichia coli (48.44%), Staphylococcus aureus (18.75%), and Candida albicans (10.93%) were the top 3 pathogenic bacteria of urine culture.Fever is one of the common complications after PCNL. Patients with high-risk factors should be given full attentions and take corresponding preventive measures targeted on risks.

Effects of a Single Rapid Infusion System on Platelet Function in Stored Whole Blood: An Ex Vivo Study

IntroductionRapid infusion systems (RIS) are used to warm and rapidly infuse crystalloids and blood products. Current guidelines do not approve of platelet transfusion through a RIS, but data supporting these guidelines are scarce. Our hypothesis was that an infusion of whole blood through a RIS would degrade platelet quantity, impede viscoelastic clot strength, and inhibit platelet aggregation response to adenosine diphosphate pathway (ADP) activation.MethodsTen iterations of a simulated scenario of transfusing whole blood via a single brand and make of RIS (Belmont Fluid Management System 2000, Belmont Medical Technologies, Billerica, MA) were performed. Units of whole blood, which were two to nine days old, were leukoreduced prestorage. Blood was used to prime the RIS and then warmed and infused at 100 mL/min into a reservoir. Blood samples were collected before and immediately after infusion. Samples were tested for platelet count, size, and viscoelastic clot strength using thromboelastographic and aggregation assays.ResultsThe study sample (n = 10) included platelets with an average age of 5.3 days. The infusion through the RIS had a detrimental effect on all the maximal amplitudes (MA) of viscoelastic testing: MA ADP (mean difference = −18.7 mm; 95% CI: −24.1 to −13.3, P = 0.004), MA rapid thromboelastography (MA rTEG) (mean difference = −6.0; 95% CI: −10.0 to −2.0, P = 0.008), MA TEG (mean difference = −7.1; 95% CI: −10.9 to −3.4, P = 0.004), mean platelet volume (MPV) (mean difference = −0.3; 95% CI: −0.6 to −0.1, P = 0.02), and platelet count (mean difference = −68.3 × 103/µL; 95% CI: −86.9 to −49.7, P = 0.004).ConclusionsPlatelet quantity, viscoelastic clot strength, and platelet aggregation response to ADP each decline after infusion through a RIS. Further studies regarding microaggregates and platelet activation are required.

Partnering With Families of Medically Complex Children Transitioning From the Hospital to Home.

Partnering With Families of Medically Complex Children Transitioning From the Hospital to Home.

Sickle Cell Disease and the Adherence to Guidelines for Use of Blood Transfusions

▪Background:An expert panel convened by the NHLBI in 2014 provided guidelines and indications for blood transfusions in patients with sickle cell disease (SCD). These recommendations were to help conserve the use of blood transfusions in SCD in order to reduce the complications of iron overload, transmission of blood-borne pathogens and development of alloantibodies. We retrospectively reviewed the charts of SCD patients who received blood during inpatient admissions and evaluated the indications for transfusions in this population.Methods:The hospital database was screened for admissions of patients with the diagnosis of SCD (HbSS, HbSβ0, HbSβ+, HbSC) who were billed for a blood transfusion between 8/1/2015 to 8/31/2016. All patients were >18 years of age. Each chart was reviewed individually to assess the clinical setting and reasons for transfusion. The following parameters were documented: age, sex, length of hospital stay (LOS), hemoglobin (Hgb) at time of transfusion, baseline Hgb, reticulocyte count, total bilirubin, number of units transfused, documented reason for transfusion, immediate reaction to transfusion, presence of alloantibodies and ferritin level. We defined the infusion of blood as a transfused event which included single or multiple units of blood. We excluded transfusions given for acute bleeding.Results:There were a total of 200 decisions to transfuse blood for 87 patients between 8/1/2015 to 8/31/2016. 72% of the patients had HbSS disease. HbSB0, HbSB+, HbSC, and unknown genotype constituted 14%, 19%, 6% and 7% of the cohort, respectively. Mean age was 30.6 years and 76% were female. A total of 434 units were transfused. The most common reasons for transfusion that deviated from guidelines were uncomplicated pain crises and a fall in Hgb (> 2g/dl, >1.5 g/dl) which accounted for 65.5% (n = 237 units) of the transfusion events (Pain 27%, Hgb drop > 2 gm 20.5% and Hgb drop > 1.5 gm 17.5%). The most common indicated guideline reasons for transfusion were symptomatic anemia and acute chest syndrome and only accounted for 12.5% and 10%, respectively of transfusions in this cohort. The mean Hgb at which patients were transfused was 6.6 g/dl, with a median value of 6.5 g/dl. The mean Hgb of those transfused for drop in hemoglobin and symptomatic anemia were 5.9 g/dl and 5.7 g/dl, respectively. The mean level of ferritin in this cohort was 2483. 15/87(17%) of patients had allo-antibodies. There was a 2% occurrence of immediate allergic blood transfusion reaction. The average LOS for all patients was 9.0 days. The average LOS for patient who received blood for uncomplicated pain or drop in Hgb was 8.9 days.Conclusion:In this group of patients with SCD, the majority of the inpatient transfusions were not indicated by national guidelines. Only 34.5% of transfusion events met expert panel recommendations. There was significant iron overload and development of allo-antibodies noted in our cohort. It is possible that there was a lack of documentation of symptoms due to anemia in those who received blood for a drop in hemoglobin. Regardless, there appears to be a significant number of unnecessary transfusions in SCD patients. We plan to develop and implement an educational program for care providers as to increase adherence to guidelines for transfusions in SCD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Safety and Tolerability of PF-04447943 across a Clinical Trial Program Including 277 Patients

▪Background: Current treatment options (eg, hydroxyurea, chronic blood infusions, and bone marrow or stem cell transplantation) for the prevention of sickle cell disease (SCD) complications vary in effectiveness and are associated with safety risks/tolerability issues. PF-04447943, a selective inhibitor of the cyclic guanosine monophosphate−specific phosphodiesterase-9A enzyme, is being developed for prophylactic therapy to reduce the incidence and/or severity of vaso-occlusive crises in patients with SCD. Herein, we report on the safety and tolerability of PF-04447943, based on a large data set from the clinical trial program.Methods: The PF-04447943 safety database includes data from 8 phase 1 studies in healthy adult and elderly subjects, a phase 2 study in patients with Alzheimer's disease (AD) from a previous development program, and a phase 1b study in stable SCD patients. Study durations ranged from 1 day to 3 months. Data are presented descriptively.Results: Safety data for 277 patients receiving PF-04447943 were available. Frequently reported treatment-emergent adverse events (TEAEs) were headache, diarrhea, and nausea, which were generally mild in severity. In the phase 1 thorough QTc (TQT) study (N=44; study duration, 28 days), at therapeutic and supratherapeutic doses, PF-04447943 was not associated with QTc interval prolongation that met the threshold of clinical concern, based on ICH E14 criteria. In the phase 2 study of the AD development program (PF-04447943, n=91; placebo, n=100; study duration 12 weeks), the incidence of TEAEs was 63.7% with PF-04447943 and 58.0% with placebo. Incidence of all-causality AEs in the gastrointestinal disorders class (including abdominal pain, diarrhea, dry mouth, dyspepsia, gastroesophageal reflux disease, intestinal obstruction, nausea, and upper gastrointestinal hemorrhage) was higher with PF-04447943 (19.8%) vs placebo (5.0%); no other notable differences were observed. In the phase 1b study in SCD patients (safety analysis set: PF-04447943, n=22; placebo, n=7; study duration, 29 days plus 28 days follow-up), nervous system disorder TEAEs (eg, headache) occurred more frequently with PF-04447943 (25 mg BID, 60.0%; 5 mg BID, 57.1%) vs placebo (28.69%). In total, 6 serious AEs (sickle cell anemia with crisis, n=4 [one patient had 3 crises, of which 2 occurred during the follow-up period]; pneumonia, n=1; biliary colic, n=1) occurred in 3 patients receiving PF-04447943; all were consistent with the course of SCD and were not considered to be treatment related.Conclusion: Review of the safety database for PF-04447943, which includes 277 patients who received the study drug, indicates that PF-04447943 is generally well tolerated, with no major safety signals. Planned long-term, phase 2 and 3 studies of PF-04447943 in patients with SCD will provide additional safety data in this population. DisclosuresCharnigo:Pfizer: Employment. Tan:Pfizer Inc: Employment. Rybin:Pfizer: Employment. Pittman:Pfizer: Employment. Sivamurthy:Pfizer Inc: Employment. Beidler:Pfizer: Employment. Clarke:Pfizer Inc: Employment.