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BACKGROUND: The etiology of anemia has tremendous overlap with the disease states responsible for cognitive decline. We used data from a perioperative database of older adults undergoing elective surgery with anesthesia to (1) examine relationships among preoperative anemia blood markers, preoperative screeners of cognitive function, and chronic disease status; and (2) examine the relationship of these factors with operative outcomes. The primary goal of this study was to investigate the association between preoperative anemia blood markers and cognition measured by a preoperative cognitive screener. Secondary goals were to (1) examine the relationship between preoperative anemia blood markers and chronic disease states (ie, American Society of Anesthesiologists [ASA] and frailty), and (2) investigate the relationship of preoperative anemia blood markers and cognition with operative outcomes (ie, discharge disposition, 1-year mortality, number of surgical complications, length of hospital stay, and length of intensive care unit [ICU] stay). METHODS: Data were collected at the University of Florida Health Shands Presurgical Center and the Perioperative Cognitive Anesthesia Network clinic within the electronic medical record. Patients 65 years of age or older were included if they had a preoperative hemoglobin (Hgb) value and a preoperative screening. Nonparametric methods were used for bivariate analysis. Logistic regression was used for the simultaneous examination of variables associated with nonhome discharge and 1-year mortality. Primary outcomes were discharge disposition and 1-year mortality. Secondary outcomes were number of surgical complications and length of hospital and ICU stay. RESULTS: Of 14,795 patients cognitively assessed, 8643 met the inclusion criteria. Of these, 26.7% were anemic, with 16.8%, 9.5%, and 0.4% having mild, moderate, and severe anemia, respectively. The Spearman correlation coefficient [95% confidence interval, CI] between the Hgb level and the clock drawing time (CDT) was -.15 [-.17 to -.13] (P < .0001) indicating that a lower Hgb level was associated with cognitive vulnerability. Hgb was also negatively correlated with the ASA physical status classification, patient Fried Frailty Index, and hospital and ICU length of stay. In the multivariable model, age, surgical service, ASA and Fried Frailty Index significantly predicted nonhome discharge. Furthermore, age, surgical service, ASA, Fried Frailty Index, and Hgb independently predicted death within 1 year of surgery. The odds of death, adjusted for ASA, Fried Frailty, and covariates, were 2.7 times higher for those in the mild anemic group compared to those who were not anemic (odds ratio [OR], 2.7, 95% CI, [2.1-3.5]). The odds of death, adjusted for ASA, Fried Frailty, and covariates, were 3.6 times higher for those in the moderate/severe anemic group compared to those who were not anemic (OR, 3.6, 95% CI, [2.7-4.9]). CONCLUSIONS: In this first medicine study, we established relationships among anemia, preoperative markers of frailty and cognition, and chronic disease states in a large cohort of older patients undergoing elective surgery in a large tertiary medical center. We found that anemia, cognitive vulnerability, and chronic health disease states predicted death within 1 year of surgery, and that these preoperative factors negatively contribute to surgical outcomes such as time in the ICU, length of hospital stay, nonhome discharge, and 1-year mortality. The World Health Organization (WHO) and many academic medical societies have urged the adoption of patient blood management (PBM) disciplines, yet anemia is not routinely optimized as a preoperative risk factor. Given the well-defined association between preoperative anemia and postoperative morbidity and mortality, performing elective surgery on an untreated anemic patient should be considered substandard care. With established safe and effective treatment regimens, iron deficiency anemia is a modifiable preoperative risk factor that should be addressed before elective surgery.
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We congratulate you on a quality review of the article on hemostasis in end-stage liver disease by Saner FH et al [...].
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Bleeding complications in patients undergoing cardiac surgery are common. The clinician must assimilate multiple sources of monitoring information, make rational decisions on the etiology of the bleeding, and then formulate a treatment strategy. Clinical decision support systems that acquire this information and present the data in an easily usable format may be useful tools to guide the physician in optimizing treatment strategies through adherence to evidence-based best practice guidelines. The authors present a narrative review of the literature and discuss how clinical decision support systems may be useful to the clinician.
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Procedimientos Quirúrgicos Cardíacos , Sistemas de Apoyo a Decisiones Clínicas , Humanos , Hemorragia/terapia , Hemorragia/etiología , Procedimientos Quirúrgicos Cardíacos/efectos adversosRESUMEN
Oxygen therapeutics have a range of applications in transfusion medicine and disease treatment. Synthetic molecules and all-natural or semi-synthetic hemoglobin-based oxygen carriers (HBOCs) have seen success as potential circulating oxygen carriers. However, many early HBOC products were removed from the market due to side effects from excess hemoglobin in the blood stream and hemoglobin entering the tissue. To overcome these issues, research has focused on increasing the molecular diameter of hemoglobin by polymerizing hemoglobin molecules or encapsulating hemoglobin in liposomal carriers, where immune responses and circulation times remain a challenge. This work looks to leverage the properties of silk fibroin, a cytocompatible and non-thrombogenic biopolymer, known to entrap protein-based cargo, to engineer a silk fibroin-hemoglobin-based oxygen carrier (sfHBOC). Herein, an all-aqueous solvent evaporation technique was used to form silk fibroin particles with and without hemoglobin to tailor the formulation for specific particle sizes. The encapsulation efficiency and ferrous state of hemoglobin were analyzed, resulting in 60% encapsulation efficiency and a maximum of 20% ferric hemoglobin, yielding 100 µg/mL active hemoglobin in certain sfHBOC formulations. The system did not elicit a strong inflammation response in vitro, demonstrating the potential for this particle system to serve as an injectable HBOC.
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Oxygen therapeutics have a range of applications in transfusion medicine and disease treatment. Synthetic molecules and all-natural or semi-synthetic hemoglobin-based oxygen carriers (HBOCs) have seen success as potential circulating oxygen carriers. However, many early HBOC products stalled in development due to side effects from excess hemoglobin in the blood stream and hemoglobin entering the tissue. To overcome these issues, research has focused on increasing the molecular diameter of hemoglobin by polymerizing hemoglobin molecules or encapsulating hemoglobin in liposomal carriers. This work leverages the properties of silk fibroin, a cytocompatible and non-thrombogenic biopolymer, known to entrap protein-based cargo, to engineer a fully protein-based oxygen carrier. Herein, an all-aqueous solvent evaporation technique was used to form silk particles via phase separation from a bulk polyvinyl alcohol phase (PVA). Particles size was tuned, and particles were formed with and without hemoglobin. The encapsulation efficiency and ferrous state of hemoglobin were analyzed, resulting in 60% encapsulation efficiency and a maximum of 20% ferric hemoglobin, yielding 100 µg/mL active hemoglobin in certain sfHBOC formulations. The system did not elicit a strong inflammation response in vitro, demonstrating the potential for this particle system to serve as an injectable HBOC.
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BACKGROUND: Antithrombin (AT) activity is reduced during cardiac operations with cardiopulmonary bypass (CPB), which is associated with adverse outcomes. Preoperative AT supplementation, to achieve >58% and <100% AT activity, may potentially reduce postoperative morbidity and mortality in cardiac operations with CPB. This prospective, multicenter, randomized, double-blind, placebo-controlled study was designed to evaluate the safety and efficacy of preoperative treatment with AT supplementation in patients at risk for low AT activity after undergoing cardiac surgery with CPB. METHODS: A total of 425 adult patients were randomized (1:1) to receive either a single dose of AT (n = 213) to achieve an absolute increase of 20% above pretreatment AT activity or placebo (n = 212) before surgery. The study duration was approximately 7 weeks. The primary efficacy end point was the percentage of patients with any component of a major morbidity composite (postoperative mortality, stroke, acute kidney injury [AKI], surgical reexploration, arterial or venous thromboembolic events, prolonged mechanical ventilation, and infection) in the 2 groups. Secondary end points included AT activity, blood loss, transfusion requirements, duration of intensive care unit (ICU), and hospital stays. Safety was also assessed. RESULTS: Overall, 399 patients (men, n = 300, 75.2%) with a mean (standard deviation [SD]) age of 66.1 (11.7) years, with the majority undergoing complex surgical procedures (n = 266, 67.9%), were analyzed. No differences in the percentage of patients experiencing morbidity composite outcomes between groups were observed (AT-treated 68/198 [34.3%] versus placebo 58/194 [29.9%]; P = .332; relative risk, 1.15). After AT infusion, AT activity was significantly higher in the AT group (108% [42-143]) versus placebo group (76% [40-110]), and lasted up to postoperative day 2. At ICU, the frequency of patients with AT activity ≥58% in the AT group (81.5%) was significantly higher ( P < .001) versus placebo group (43.2%). Secondary end point analysis did not show any advantage of AT over placebo group. There were significantly more patients with AKI ( P < .001) in the AT group (23/198; 11.6%) than in the placebo group (5/194, 2.6%). Safety results showed no differences in treatment-emergent adverse events nor bleeding events between groups. CONCLUSIONS: AT supplementation did not attenuate adverse postoperative outcomes in our cohort of patients undergoing cardiac surgery with CPB.
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Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Lesión Renal Aguda/etiología , Adulto , Anciano , Antitrombinas/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Puente Cardiopulmonar/efectos adversos , Suplementos Dietéticos , Método Doble Ciego , Humanos , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
This case report demonstrates a small repetition of the case series carried out in Italy wherein inhaled adenosine was administered to patients experiencing severe and worsening coronavirus disease-2019 (COVID-19). The two cases are important not only because they were the first of their type in the United States, but also because both patients were DNR/DNI and were therefore expected to die. Study repetition is vitally important in medicine. New work in pharmacology hypothesizes that adenosine-regulator proteins may play a role in the pathogenesis of COVID-19 infection. Furthermore, adenosine, by interacting with cell receptor sites, has pluripotent effects upon inflammatory cells, is anti-inflammatory, and is important in tissue hypoxia signaling. Inhaled adenosine is potentially safe; thousands have received it for asthmatic challenge testing. The effects of adenosine in these two cases were rapid, positive, and fit the pharmacologic hypotheses (as seen in prior work in this journal) and support its role as a therapeutic nucleoside.
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BACKGROUND: Perfluorocarbon emulsions (PFCs) are intravenous artificial oxygen carriers with enhanced gas solubility. As lipid micelle nanoparticle emulsions, PFCs may have a class effect that causes degrees of thrombocytopenia. Understanding the extent of the platelet effects, including mechanism and potential inflammation after PFC infusion, is important for safe human trials. METHODS: Normal sheep (Dorper) were infused with 5 mL/kg of Oxygent (w/v 60% PFC) or Perftoran (w/v 20% PFC). Controls received 6% Hetastarch or were naive. Blood samples were analyzed from baseline, time 0 (the end of infusion), 3 and 24 hours, and 4 and 7 days. Platelet count, plateletcrit, mean platelet volume, platelet distribution width, and CD-62p (a platelet activation-dependent membrane protein) were measured. Neutrophils, monocytes, and total white blood cell counts were analyzed. RESULTS: In these inflammatory cell lines, there were no consistent changes or cellular activation after PFC infusion. A decrease (<10% from baseline and naive controls) in platelet count was seen on day 4 after Oxygent infusion (3 g/kg), which recovered by day 7. No platelet effect was seen in Perftoran (1 g/kg). Plateletcrit, mean platelet volume, and platelet distribution width did not change significantly at any time point among the groups. CD-62p, ADP, and collagen aggregometry showed no significant change in platelet function. CONCLUSION: There was no evidence of overall reduction in platelet number, or any correlation with the change in platelet activation or inhibition. Therefore, the risk of increased thrombosis/bleeding after PFC intravenous infusion is low in this non-trauma sheep model.
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Fluorocarburos , Animales , Plaquetas/metabolismo , Fluorocarburos/metabolismo , Fluorocarburos/farmacología , Infusiones Intravenosas , Activación Plaquetaria , Recuento de Plaquetas , OvinosRESUMEN
Central venous and arterial access through minimally invasive techniques has been described in adult pigs. This article demonstrates success in juvenile animals. Using ultrasound guidance and the modified Seldinger technique, 5 Fr/15 cm single-lumen central venous catheters and 20 Ga 4.5 cm femoral arterial catheters were placed in six Yorkshire cross-bred swine. All six cases had no loss of venous catheter patency or infection during the 96-hour follow-up period. Arterial catheters remained patent, and no significant bleeding was noted after removal.
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Cateterismo Venoso Central , Venas Yugulares , Animales , Catéteres de Permanencia , Venas Yugulares/diagnóstico por imagen , Porcinos , Ultrasonografía , Ultrasonografía IntervencionalRESUMEN
We retrospectively compared anticoagulation with heparin and bivalirudin for 32 consecutive children under 18 years old during extracorporeal membrane oxygenation (ECMO) in our pediatric cardiac intensive care unit (PCICU). Between September 2015 and January 2018, 14 patients received heparin, 13 venoarterial (VA), and 1 venovenous (VV). From February 2018 to September 2019, 18 received bivalirudin (all VA). The mean (standard deviation [SD]) percentage of time with therapeutic activated partial thromboplastin time and activated clotting time was bivalirudin 54 (14%) and heparin 57 (11%), p = 0.4647, and percentage of time supratherapeutic was bivalirudin 18 (10%) and heparin 27 (12%), p = 0.0238. Phlebotomy-associated blood loss per hour of ECMO was double in the heparin compared with bivalirudin group 1.08 ml/h (0.20 ml/h), compared with 0.51 ml/h (0.07 ml/h), p = 0.0003, as well as interventions to control bleeding. Packed red blood cell (PRBC) transfusions significantly correlated with higher blood loss in the heparin group (Pearson correlation coefficient = 0.49, p = 0.0047). Overall amount of blood product utilization was not different between the groups. Survival to ECMO decannulation was 89% for bivalirudin and 57% for heparin, p = 0.0396, although 6 month survival was not significantly different (67% versus 57%, p = 0.5809). Heparin may increase the need for PRBC transfusions and strategies to attenuate bleeding when compared with bivalirudin for children receiving ECMO in PCICU.
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Anticoagulantes/uso terapéutico , Transfusión de Eritrocitos , Oxigenación por Membrana Extracorpórea , Fragmentos de Péptidos/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Heparina/uso terapéutico , Hirudinas , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico , Masculino , Proteínas Recombinantes/uso terapéutico , Estudios RetrospectivosRESUMEN
The authors developed a process to produce a reliably fitting face mask from materials that were immediately available to health care workers, to reduce the risk of infection. Multiple materials and designs were developed to produce face masks that focused on ease of production, the ability to generate a reliable facial seal, and the ability to tailor the mask for those who did not fit commercially available N95 masks. Two final designs were selected. Mask components were assembled into kits and distributed to community sewists. Plan-Do-Study-Act cycles were developed for quality improvement. A process was successfully developed to produce 5000 face masks in a period of 3 weeks that fit almost all (95%) health care workers who did not fit in a commercially available mask. The process was able to produce quality face masks with specific attention paid to developing masks that would pass qualitative fit testing.
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COVID-19/prevención & control , Participación de la Comunidad/métodos , Máscaras/provisión & distribución , Humanos , Máscaras/normasRESUMEN
Solid tumors have abnormal microcirculation that limits oxygen delivery and leads to a hypoxic tumor microenvironment. Tumor hypoxia stabilizes the transcription factor HIF-1α that can trigger immunosuppression through A2A adenosine receptors which prevents immune attack on tumors. In addition, success of chemotherapy and radiation therapy appears to be dependent on oxygen levels. Two main pharmaceutical classes of agents (hemoglobin based and perfluorocarbon man-made carbon oils) have been tested in tumor models as enhanced oxygen therapeutics. This article will review how these agents function as well as examine work to date with both drug classes.
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Fluorocarburos/administración & dosificación , Hemoglobinas/administración & dosificación , Neoplasias/tratamiento farmacológico , Oxígeno/administración & dosificación , Hipoxia Tumoral/efectos de los fármacos , Animales , HumanosRESUMEN
End-stage lung disease and advanced cardiac conditions are frequently seen together and represent a clinical dilemma. Even though both issues may be amenable to surgical management, combining lung transplant with surgical valve repair is rarely done and theoretically associated with increased morbidity and mortality risks, especially in elderly patients. Here, we describe 2 patients presenting with end-stage lung disease and significant aortic stenosis who were successfully bridged to lung transplant via transcatheter aortic valve replacement. Patient 1 was a 66-year-old man who underwent a double lung transplant 56 days after transcatheter aortic valve replacement. Patient 2 was a 70-year-old man who underwent a single right lung transplant 103 days after transcatheter aortic valve replacement. Both patients had uneventful postoperative courses and are alive at the 1-year time point with excellent performance status. This report suggests that transcatheter aortic valve replacement may favorably impact lung transplant candidacy for patients with end-stage lung disease in the setting of severe aortic stenosis, likely representing a better alternative to concomitant aortic valve replacement and lung transplant in elderly patients.
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Estenosis de la Válvula Aórtica , Trasplante de Pulmón , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Humanos , Masculino , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and "flattening the curve" while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient's own blood. This multinational and diverse group of authors issue this "Call to Action" underscoring "The Essential Role of Patient Blood Management in the Management of Pandemics" and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.
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Bancos de Sangre/organización & administración , Transfusión Sanguínea , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Donantes de Sangre , COVID-19 , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/transmisión , Medicina Basada en la Evidencia , Humanos , Neumonía Viral/terapia , Neumonía Viral/transmisiónRESUMEN
PURPOSE: Hydroxocobalamin, or vitamin B12 (V-B12), is frequently used to treat smoke inhalation and cyanide poisoning. Recent reports have also described its use to treat vasoplegia in cardiac surgery and liver transplantation. This narrative review discusses this "off-label" indication for V-B12, focusing on the potential biochemical mechanisms of its actions. SOURCE: PubMed, Cochrane, and Web of Science databases were searched for clinical reports on the use of V-B12 for vasoplegia in cardiac surgery and liver transplantation, with the biochemical mechanisms discussed being based on a survey of the related biochemistry literature. PRINCIPAL FINDINGS: Forty-four patients have been treated with V-B12 for vasoplegia in various isolated case reports and one series. Although 75% of patients have increased blood pressure in response to V-B12, there were some "non-responders". The true efficacy remains unknown because clinical trials have not been performed, and significant reporting bias likely exists. Plausible biochemical explanations exist for the potential beneficial effects of V-B12 in treating vasoplegia, including binding nitric oxide and other gasotransmitters. Additional research is required to clarify if and how these mechanisms are causally involved in effective clinical responders and non-responders. CONCLUSIONS: Although anecdotal reports utilizing V-B12 for vasoplegia are available, no higher-level evidence exists. Future work is necessary to further understand the dosing, timing, adverse events, and biochemical mechanisms of V-B12 compared with other therapies such as methylene blue.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Intraoperatorias/tratamiento farmacológico , Complicaciones Intraoperatorias/metabolismo , Trasplante de Hígado/efectos adversos , Vasoplejía/tratamiento farmacológico , Vasoplejía/metabolismo , Vitamina B 12/uso terapéutico , Vitaminas/uso terapéutico , Humanos , Óxido Nítrico/metabolismoRESUMEN
BACKGROUND: Fluid resuscitation plays a prominent role in stabilizing trauma patients with hemorrhagic shock yet there remains uncertainty with regard to optimal administration time, volume, and fluid composition (e.g., whole blood, component, colloids) leading to complications such as trauma-induced coagulopathies (TIC), acidosis, and poor oxygen transport. Synthetic fluids in combination with antioxidants (e.g., vitamin C) may resolve some of these problems. OBJECTIVES: We applied quantitative mass spectrometry-based proteomics [liquid chromatography-mass spectrometry (LC-MS/MS)] to map the effects of fluid resuscitation and intravenous vitamin C (VitC) in a pig model of polytrauma (hemorrhagic shock, tissue injury, liver reperfusion, hypothermia, and comminuted bone fracture). The goal was to determine the effects of VitC on plasma protein expression, with respect to changes associated with coagulation and trauma-induced coagulopathy (TIC). METHODS: Longitudinal blood samples were drawn from nine male Sinclair pigs at baseline, 2 h post trauma, and 0.25, 2, and 4 h post fluid resuscitation with 500 mL hydroxyethyl starch. Pigs were treated intravenously (N = 3/treatment group) with saline, 50 mg VitC/kg (Lo-VitC), or 200 mg VitC/kg (Hi-VitC) during fluid resuscitation. RESULTS: A total of 436 plasma proteins were quantified of which 136 changed following trauma and resuscitation; 34 were associated with coagulation, complement cascade, and glycolysis. Unexpectedly, Lo-VitC and Hi-VitC treatments stabilized ADAMTS13 levels by ~4-fold (P = .056) relative to saline and enhanced ADAMTS13/von Willebrand factor (VWF) cleavage efficiency based on LC-MS/MS evidence for the semitryptic VWF cleavage product (VWF1275-1286 ). CONCLUSIONS: This study provides the first comprehensive map of trauma-induced changes to the plasma proteome, especially with respect to proteins driving the development of TIC.
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Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Coagulación Sanguínea , Proteínas Sanguíneas/metabolismo , Fluidoterapia , Traumatismo Múltiple/terapia , Resucitación , Choque Hemorrágico/terapia , Administración Intravenosa , Animales , Biomarcadores/sangre , Cromatografía Liquida , Modelos Animales de Enfermedad , Masculino , Traumatismo Múltiple/sangre , Proteómica , Choque Hemorrágico/sangre , Sus scrofa , Espectrometría de Masas en Tándem , Factores de TiempoRESUMEN
BACKGROUND: Delayed hemolytic transfusion reaction (DHTR) with hyperhemolysis is a potentially fatal complication resulting from alloimmunization that can cause severe hemolysis of both transfused and intrinsic red blood cells (RBCs). Patients with sickle cell disease often receive multiple RBC units during their lifetime and thus are likely to develop alloantibodies that increase the risk for DHTR. Treatment to decrease hemolysis includes intravenous immunoglobulin (IVIG), steroids, eculizumab, rituximab, and plasmapheresis in addition to erythropoietin (EPO), intravenous (IV) iron, vitamin B12, and folate to support erythropoiesis. RBC transfusion is preferably avoided in DHTR due to an increased risk of exacerbating the hemolysis. CASE REPORT: We report a rare case of anti-N and anti-Doa immunoglobulin (Ig)G alloantibody-mediated life-threatening DHTR with hyperhemolysis in a patient with hemoglobin SS after RBC transfusion for acute chest syndrome who was successfully treated with eculizumab and HBOC-201 (Hemopure) in addition to steroids, IVIG, EPO, IV iron, and vitamin B12. HBOC-201 (Hemopure) was successfully used as a RBC alternative in this patient. CONCLUSION: Anti-N and anti-Doa IgG alloantibodies can rarely cause severe life-threatening DHTR with hyperhemolysis. HBOC-201 (Hemopure) can be a lifesaving alternative in this scenario. Our report also supports the use of eculizumab in DHTR; however, prospective studies are needed to determine the appropriate dose and sequence of eculizumab administration.
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Anemia de Células Falciformes/terapia , Anticuerpos Monoclonales Humanizados/administración & dosificación , Hemoglobinas/administración & dosificación , Hemólisis/inmunología , Inmunoglobulina G/sangre , Isoanticuerpos/sangre , Reacción a la Transfusión/etiología , Adulto , Anemia Hemolítica Autoinmune/sangre , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/inmunología , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/inmunología , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/inmunología , Femenino , Hemoglobinas/efectos adversos , Hemoglobinas/inmunología , Humanos , Inmunoglobulina G/fisiología , Isoanticuerpos/fisiología , Factores de Tiempo , Reacción a la Transfusión/sangre , Reacción a la Transfusión/inmunologíaRESUMEN
Essentials Platelets in trauma-induced coagulopathy (TIC) are impaired, but the mechanism is not known. We performed comprehensive longitudinal platelet function testing in trauma patient samples. Platelets in TIC are widely impaired early after injury, but platelet activatability is intact. This suggests a mechanism of transient platelet cytoskeletal/integrin dysfunction during TIC. SUMMARY: Background Trauma-induced coagulopathy (TIC) is a common and deadly bleeding disorder. Platelet dysfunction is present during TIC, but its mechanisms remain unclear. Platelets are currently thought to become "exhausted," a state in which they have released their granule contents and can no longer aggregate or contract. Methods This prospective observational cohort study tested the hypothesis that platelet exhaustion is present during TIC and characterized the early time course of platelet dysfunction. Blood was collected from 95 adult trauma patients at a Level I trauma center at time of Emergency Department arrival and several time points over 72 h. Platelet activation state and function were characterized using CD62P (P-selectin) and PAC-1 surface membrane staining, platelet function analyzer (PFA-100), aggregometry, viscoelastic platelet mapping, and, to test for exhaustion, their ability to express CD62P after ex vivo adenosine diphosphate (ADP) agonism. Platelet function was compared between patients with and without TIC, defined by prothrombin time ≥18 s. Results Platelets in TIC showed no initial increase in their level of surface activation markers or impairment of their capacity to express CD62P in response to ADP stimulation. However, TIC platelets were impaired in nearly all functional assays, spanning adhesion, aggregation, and contraction. These effects largely remained after controlling for platelet count and fibrinogen concentration and resolved after 8 h. Conclusion The TIC platelets exhibit early impairment of adhesion, aggregation, and contraction with retained alpha granule secretion ability, suggesting a specific mechanism of cytoskeletal or integrin dysfunction that is not a result of more general platelet exhaustion.