Comparison of the resonance sonorheometry based Quantra® system with rotational thromboelastometry ROTEM® sigma in cardiac surgery - a prospective observational study.

BACKGROUND: Measures of the sonorheometry based Quantra® viscoelastic hemostatic analyzer (HemoSonics, LCC, Charlottesville, VA, USA) were compared with corresponding results of the ROTEM® sigma device (Instrumentation Laboratory, Bedford, MA, USA). METHODS: In thirty-eight patients scheduled for elective cardiac surgery between December 2018 and October 2019, blood samples were taken after induction of anesthesia (sample 1) and after heparin neutralization (sample 2) and measured on Quantra (QPlus® Cartridge) and ROTEM sigma (ROTEM® sigma complete + hep Cartridge). Clot times and clot stiffness values were recorded. Clot stiffness values of ROTEM amplitudes (A in mm) were converted to shear modulus (G) in hectoPascal (hPa): G (hPa) = (5 x A)/(100-A). Additionally, time-to-results was recorded. Spearman rank test correlation and Bland Altman analysis were performed. RESULTS: Clot stiffness parameters of the Quantra correlated strongly with corresponding measurements of the ROTEM with r = 0.93 and 0.94 for EXTEM A10 vs CS and r = 0.94 and 0.96 for FIBTEM A10 vs FCS for sample 1 and 2, respectively. Quantra clot time correlated strongly with ROTEM INTEM CT with r = 0.71 for sample 1 and r = 0.75 for sample 2. However, Bland Altman analysis showed no agreement in all compared assays of both methods. The median time to delivery of first and complete results was significantly shorter for Quantra (412 and 658 s) compared to ROTEM sigma (839 and 1290 s). CONCLUSIONS: The Quantra showed a strong correlation with the ROTEM sigma for determining clot times and clot stiffness and the parameters assess similar aspects of clot development. However, these parameters are not directly interchangeable and implicate that separate cut-off values need to be established for users of the Quantra device. Word count: 278. TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov (ID: NCT04210830 ) at December 20th 2019.

Treatment of Seizures in Children and Adults in the Emergency Medical System of the City of Zurich, Switzerland - Midazolam vs. Diazepam - A Retrospective Analysis.

INTRODUCTION: Seizures count to critical situations emergency medical systems (EMS) are confronted with. OBJECTIVES: Evaluation of a modified treatment algorithm (MTAS-EMS) using diazepam and midazolam due to a supply bottleneck of iv lorazepam in 2012. METHODS: Retrospective study where data from patients treated for seizures by the EMS of the city of Zurich were analyzed. Effectiveness of the MTAS-EMS and i.v. diazepam in children and adults was compared with respect of cessation of seizure without recurrence over the period until arrival at the hospital. The chi-square and Fisher's exact test were used to compare categorical data. The Student's t-test and Mann Whitney test were used to compare numerical data. p-values < 0.05 are considered significant. RESULTS: Of 584 documented missions, 165 treated patients (126 adults and 39 children) were included. 115 patients (80 adults and 35 children) were treated according the MTAS-EMS. Cessation of seizure was achieved in 85% of the adults and in 97% of the children, if all options of the MTAS-EMS were used. The first dose of nasal midazolam was more successful in children compared to adults (p = 0.012). In adults, the single dose of i.v. diazepam terminated the seizure in 98% (p = 0.001) compared to 57% for the single dose of iv and 64% for nasal midazolam. CONCLUSIONS: The treatment success of the MTAS-EMS is high. However, in adults the single dose of i.v. diazepam is as successful as the completely used MTAS-EMS and seems to be superior to the single dose iv and nasal midazolam.

Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial.

BACKGROUND: Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. This study assessed whether immediate preoperative treatment could result in reduced perioperative red blood cell (RBC) transfusions and improved outcome. METHODS: In this single-centre, randomised, double-blind, parallel-group controlled study, patients undergoing elective cardiac surgery with anaemia (n=253; haemoglobin concentration (Hb) <120 g/L in women and Hb <130 g/L in men) or isolated iron deficiency (n=252; ferritin <100 mcg/L, no anaemia) were enrolled. Participants were randomly assigned (1:1) with the use of a computer-generated range minimisation (allocation probability 0·8) to receive either placebo or combination treatment consisting of a slow infusion of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery. Primary outcome was the number of RBC transfusions during the first 7 days. This trial is registered with ClinicalTrials.gov, number NCT02031289. FINDINGS: Between Jan 9, 2014, and July 19, 2017, 1006 patients were enrolled; 505 with anaemia or isolated iron deficiency and 501 in the registry. The combination treatment significantly reduced RBC transfusions from a median of one unit in the placebo group (IQR 0-3) to zero units in the treatment group (0-2, during the first 7 days (odds ratio 0·70 [95% CI 0·50-0·98] for each threshold of number of RBC transfusions, p=0·036) and until postoperative day 90 (p=0·018). Despite fewer RBC units transfused, patients in the treatment group had a higher haemoglobin concentration, higher reticulocyte count, and a higher reticulocyte haemoglobin content during the first 7 days (p≤0·001). Combined allogeneic transfusions were less in the treatment group (0 [IQR 0-2]) versus the placebo group (1 [0-3]) during the first 7 days (p=0·038) and until postoperative day 90 (p=0·019). 73 (30%) serious adverse events were reported in the treatment group group versus 79 (33%) in the placebo group. INTERPRETATION: An ultra-short-term combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid reduced RBC and total allogeneic blood product transfusions in patients with preoperative anaemia or isolated iron deficiency undergoing elective cardiac surgery. FUNDING: Vifor Pharma and Swiss Foundation for Anaesthesia Research.

Short term general anesthesia for retro-bulbar block in ophthalmic surgery generates no significant hypercapnia.

To assess the impact of short time hypnosis for retro-bulbar anesthesia on ventilation in patients undergoing ophthalmic surgery of the anterior eye chamber. In all patients, a combined continuous transcutaneous carbon dioxide tension (PtcCO2) and partial oxygen saturation (SpO2) measurement was applied in addition to routine monitoring. To enable unconscious application of retro-bulbar anesthesia, intravenous thiopental was given in one to multiple bolus doses. Transient breathing support included chin lift, Esmarch maneuver and manual hand-bag ventilation via face mask. Main endpoints were apnea time, recovery time according to the Richmond Agitation Sedation Scale, as well as SpO2 and PtcCO2 readings at predefined time points. Fifty-two patients with a mean age of 68 ± 13 years were included. Average thiopental dose was 2.7 ± 0.6 mg/kg. In seven (13.5%) patients repeated doses of thiopental were necessary to a total of 3.3 ± 1.1 mg/kg. Except one patient, no severe, significant or clinical relevant hypercapnia or desaturation periods were observed, and the occurring elevation of PtcCO2 values did not correlate with the application of repeated doses of thiopental or the need for the Esmarch maneuver. Higher PtcCO2 values were associated with the presence of hypertension and smoking. Apnea (p < 0.001) and recovery (p = 0.003) time were significantly prolonged in the patients needing the Esmarch maneuver. Short term anesthesia with thiopental in ophthalmic surgery is associated with a mild but not clinically relevant hypercapnia.

The Impact of Prehospital Tranexamic Acid on Blood Coagulation in Trauma Patients.

BACKGROUND: There is limited data on prehospital administration of tranexamic acid (TXA) in civilian trauma. The aim of this study was to evaluate changes in coagulation after severe trauma from on-scene to the hospital after TXA application in comparison to a previous study without TXA. METHODS: The study protocol was registered at ClinicalTrials.gov (NCT02354885). A prospective, multicenter, observational study investigating coagulation status in 70 trauma patients receiving TXA (1 g intravenously) on-scene versus a control group of 38 patients previously published without TXA. To account for potential differences in patient and trauma epidemiology, crystalloid and colloidal resuscitation fluid, 2 propensity score matched groups (n = 24 per group) were created. Measurements included ROTEM, standard coagulation tests and blood gas analyses on-scene and emergency department admission. Presented values are mean and [standard deviation], and difference in means and 95% confidence intervals. RESULTS: Patient epidemiology was not different between groups. Coagulation assays on-scene were comparable between the TXA and C. Prehospital hyperfibrinolysis was blunted in all 4 patients in the TXA group. Viscoelastic FIBTEM maximum clot firmness (MCF), representing functional fibrinogen levels, did not change from on-scene to the emergency department in the TXA group, whereas MCF decreased -3.7 [1.8] mm in the control group. Decrease of MCF was significantly reduced in the TXA group in EXTEM by 9.2 (7.2-11.2) mm (P < .001) and INTEM by 6.8 (4.7-9.0) mm (P < .001) in favor of the TXA group. Production of fibrinogen fragments (represented by D-dimers) was significantly lower in the TXA group compared to group C. CONCLUSIONS: Early prehospital administration of TXA leads to clot stabilization and a reduction of fibrinolytic activity, causing a decrease in fibrin degradation products buildup (D-dimer).

Quarantine versus pathogen-reduced plasma-coagulation factor content and rotational thromboelastometry coagulation.

BACKGROUND: Different types of fresh-frozen plasma (FFP) exist, and the concentrations of plasma proteins vary between individuals and blood groups. Furthermore, processing may also influence the content. Quarantine-stored plasma (qFFP) and plasma that was pathogen-reduced using blood-safety (Intercept) technology (piFFP) were analyzed regarding procoagulant and anticoagulant hemostasis proteins, including endogenous thrombin (thrombin-generation) potential (ETP). MATERIALS AND METHODS: Thirty-five samples of each type of FFP were analyzed using only male Blood Group O donors. FFP units were stored frozen for comparable periods of time before plasma protein content was assessed. Once the units were thawed, all tests were completed within 4 hours. The results are presented as means ± standard deviations or as median (minimum; maximum) and were compared using independent-sample t tests (significance, p < 0.01). RESULTS: Significantly higher concentrations of adintegrin-like and metalloprotease with thrombospondin type-13 motifs (ADAMTS13), fibrinogen, Factor (F)V, FVIII, FXIII, protein S, protein S activity, antithrombin, microvesicle (<900 nm), and α2 antiplasmin were observed in qFFP. The variability of factors was significantly lower in piFFP. Tissue factor (TF) at 1 picomolar (pM) exhibited significantly longer lag time, a lower peak, lower ETP, and a lower velocity index in qFFP compared with piFFP. In TF at 5 pM, significant differences in lag time (longer in qFFP), velocity index (lower in qFFP), and peak (lower in qFFP) were observed. Rotational thromboelastometry revealed a significantly longer (p = 0.002) clot-formation time with intrinsic thromboelastometry for piFFP and a significantly shorter clotting time (p = 0.004) with thromboelastometry fibrinogen testing for piFFP. CONCLUSION: Pathogen reduction reduces procoagulant and anticoagulant coagulation factors as well as variability. A thrombin-generation assay showed no reduced ETP and no supraphysiological thrombin generation. None of the FFP preparations is likely to be effective for treating fibrinogen deficiency.

Accuracy of non-invasive continuous total hemoglobin measurement by Pulse CO-Oximetry in severe traumatized and surgical bleeding patients.

The Masimo Radical-7 Pulse CO-Oximeter (Masimo Corp., USA) non-invasively computes hemoglobin concentration (SpHb). SpHb was compared to Co-Oximeter readings (CoOxHb) of arterial samples in surgery patients of the emergency department. Forty-six patients were enrolled. The Masimo R1 25L (revision F and G) adult adhesive sensor was attached to the ring finger of the arterially cannulated hand. Before start, every 30 min during surgery and in the case of severe bleeding SpHb and CoOxHb values were documented. SpHb and post hoc adjusted SpHb (AdSpHb) values were analyzed. Linear regression analysis and Bland-Altman plot for agreement were performed. The detection failure rate of SpHb was 24.5 %. CoOxHb and SpHb showed a strong correlation (r = +0.81), but agreement was moderate [bias (LOA) of -0.6 (-3.0; +1.9)] g/dl. Positive and negative predicted value was 0.49 and 0.69. Exclusion of changes of CoOxHb values ≤1 g/dl resulted in a positive and negative predictive value of 0.66 and 1.00. Post hoc adjustment of the SpHb (AdSpHb) improved linear correlation of CoOxHb and AdSpHb [r = +0.90 (p < 0.001)] but less the agreement [bias (LOA) of CoOxHb and AdSpHb = -0.1 (-2.1/+1.9) g/dl]. SpHb agreed only moderately with CoOxHb values and predicted decreases of CoOxHb only if changes of SpHb ≤ 1.0 g/dl were excluded. The detection failure rate of SpHb was high. At present, additional refinements of the current technology are necessary to further improve performance of non-invasive hemoglobin measurement in the clinical setting.

Perioperative blood conservation strategies for major spine surgery.

BACKGROUND: Orthopedic surgery, especially spine and spinal deformity surgery, may be associated with high perioperative blood loss. In order to reduce the risk of excessive blood loss and unnecessary blood transfusions, strategies such as Patient Blood Management including goal-directed coagulation management have been developed. RECENT FINDINGS: Adverse effects of allogeneic blood transfusions have been shown for most surgical fields including orthopedic surgery. Several efforts have been made to increase the preoperative red blood cell (RBC) mass, to reduce the intraoperative blood loss, and to use restrictive transfusion triggers in order to minimize or avoid RBC transfusions. Measures to reduce intraoperative blood loss include new surgical techniques, use of cell salvage where possible, bedside coagulation management with point-of-care devices, substitution of coagulation factors, antifibrinolytic agents, and desmopressin, induced hypotension, and avoidance of hypothermia. SUMMARY: Blood conservation in spinal surgery is a multidisciplinary approach and the efficacy of most single measures has been shown. Cost-effectiveness and the benefits of long-term patient outcomes are the subjects of current and future research.

Point of care and factor concentrate-based coagulation algorithms.

In the last years it has become evident that the use of blood products should be reduced whenever possible. There is increasing evidence regarding serious adverse events, including higher mortality and morbidity, related to transfusions. The use of point of care (POC) devices integrated in algorithms is one of the important mechanisms to limit blood product exposure. Any type of algorithm, especially the POC-based ones, allows goal-directed transfusions of blood products and even better targeted factor concentrate substitutions. Different types of algorithms in different surgical settings (cardiac surgery, trauma, liver surgery etc.) have been established with growing interest in their use as they offer objective therapy for management and reduction of blood product use. The use of POC devices with evidence-based algorithms is important in the bleeding patient independent of its origin (traumatic vs. surgical). The use of factor concentrates compared to the classical blood products can be cost-saving, beneficial for the patient, and in agreement with the WHO-requested standard of care. The empiric and uncontrolled use of blood products such as fresh frozen plasma, red blood cells, and platelets without POC monitoring should no longer be followed with regard to actual evidence in literature. Furthermore, the use of factor concentrates may provide better outcomes and potential for cost saving.

Reliability of the volatile agent consumption display in the Draeger Primus™ anesthesia machine.

Knowledge of the consumed amount of volatile anesthetic (VA) expressed in liquid agent is necessary to enable agent sparing dosing measures and for billing purposes. The widespread Draeger Primus™ anesthesia machine displays in its logbook the amount of consumed VA at the end of each anesthesia, but the reliability of this parameter is yet unknown. The objective was to evaluate the precision and reliability of the inbuilt VA consumption display in Draeger Primus™ anesthesia machines as compared with the gold standard of weighing the vaporizer before and after anesthesia. In this prospective laboratory investigation we compared the VA consumption displayed by the Draeger Primus™ anesthesia machine with measured vaporizer weight differences before and after 10 sevoflurane and 10 desflurane anesthesias. We assessed the average difference and spread of values between the predicted (displayed) and measured (control) values for VA consumption. The displayed sevoflurane consumption overestimated the measured values by 4.3 ± 5.4 ml (7.6%). The displayed desflurane consumption underestimated the measured values by -3.5 ± 6.3 ml (6.2%). Nine from 10 sevoflurane pairs of values and all desflurane pairs of values were within ±1.96 SD. The displayed VA consumption calculations for sevoflurane and desflurane in the Draeger Primus™ are sufficiently reliable to estimate the pharmacoeconomic impact of VA delivery during inhalational anesthesia.

Changes in coagulation in standard laboratory tests and ROTEM in trauma patients between on-scene and arrival in the emergency department.

BACKGROUND: When trauma patients arrive in the emergency department (ED), coagulopathy frequently is present. The time course, however, in which this coagulopathy develops is poorly understood. No study has fully evaluated the coagulation status, including thromboelastometry on-scene and at hospital arrival. We hypothesized that measured coagulation variables might change when measured at the scene of injury and upon arrival to the ED. METHODS: We performed a prospective, single-center, observational study investigating coagulation status in 50 trauma patients on-scene and at arrival in the ED. Measurements included arterial blood gases, ROTEM®, protein S100, protein C activity, protein S, Quick value, international normalized ratio, activated partial thromboplastin time, D-dimer, coagulation factor V (FV), coagulation factor XIII (FXIII), fibrinogen, hemoglobin, hematocrit, platelets, and volume and blood products being administered during the first 24 hours. RESULTS: Significant changes between on-scene and the ED were observed for the following values: partial venous oxygen pressure increased and sodium, glucose, and lactate decreased. For EXTEM, INTEM, and APTEM, clotting time and clot formation time increased significantly, whereas maximal clot firmness and angle α decreased significantly (all P ≤ 0.004). For FIBTEM, clotting time increased significantly and maximal clot firmness decreased significantly. In the laboratory, significant reductions in hemoglobin, hematocrit, platelets, activated partial thromboplastin time, fibrinogen, FV, FXIII, protein C activity, protein S, and protein S100 were observed (all P ≤ 0.001). CONCLUSIONS: Although most all laboratory and rotational thromboelastometry coagulation tests worsened over time when measured on-scene and in the ED, monitoring coagulation at the scene of trauma does not provide clinically important information in a majority of trauma patients. One hour after injury, significant activation and consumption of fibrinogen, FV, FXIII, protein C activity, and protein S were observed.

[A WHO concept- patient blood management]. / Ein WHO Konzept - Patient Blood Management.

Blood transfusions are in general considered as lifesaving. Current data and evidence show, that blood transfusions are associated with increased morbidity and mortality, and this apparently dose-dependent. Basic research and results from randomized controlled trials show a causal relationship between blood transfusion and adverse outcome. Based on the current state of knowledge it has to be questioned that blood transfusions are "life-saving" as patients are exposed to an increased risk of disease or death. Furthermore, blood transfusions are more costly than previously assumed. For these reasons novel approaches in the treatment of anemia and bleeding are needed. Patient Blood Management (PBM) allows reduction of transfusion rates by correcting anemia by stimulating erythropoiesis, minimizing perioperative blood loss and optimizing the physiological tolerance of anemia. In 2010 the World Health Organization has claimed PBM to be considered as golden standard. PBM reduces morbidity and mortality by lowering the excessive use of blood transfusions. This concept has partially and successfully been implemented in the University Hospital Balgrist in Zurich.

A l'heure actuelle les transfusions sanguines sont généralement considérées comme salvatrices. Les données actuelles par contre montrent que les transfusions sanguines sont associées, et cela clairement en fonction des doses appliquées, à une morbidité et mortalité augmentées. Outre différentes tentatives d'explication fournies par la recherche fondamentale, les résultats récents d'études contrôlées et randomisées ont clairement démontré qu'il s'agit d'une relation de cause à effet. Pour cela l'opinion que des transfusions sanguines sont salvatrices doit être revue de façon critique car ce traitement peut promouvoir des maladies et même représenter un danger vital. En plus les transfusions sanguines génèrent des coûts beaucoup plus élevés que présumé jusqu'à présent. En cas d'anémie ou de saignement de nouveaux concepts de traitements comme le «patient blood management¼ (PBM) sont indispensables et essentiels. Le PBM réduit la nécessité de transfusions en corrigeant l'anémie par des substances stimulant l'érythropoïèse, en réduisant les pertes sanguines durant l'intervention chirurgicale et en augmentant la tolérance physiologique de l'anémie. Une résolution de l'organisation mondiale de la santé en 2010 exige que le PBM soit considéré comme «le golden standard¼ pour le traitement des patients. La réduction de l'utilisation de produits sanguins peut clairement diminuer la mortalité et morbidité. Depuis que le concept a partiellement été introduit à l'hôpital universitaire Balgrist, Zurich et montre clairement des résultats positifs.

Transfusion strategy in multiple trauma patients.

PURPOSE OF REVIEW: To point out the tolerance of anemia, the possible use of alternatives to allogeneic blood products as well as the pathophysiological effects of transfusions in the context of multiple trauma patients. RECENT FINDINGS: Restrictive transfusion triggers are beneficial for patient outcome in trauma.The actual European Trauma Treatment Guidelines suggest the use of point-of-care devices, the use of transfusion algorithms and factor concentrates to control coagulopathy. The use of high ratios of plasma to red blood cells to improve survival has been shown to suffer from a time-dependent survival bias. In massive bleeding, factor-based treatment of coagulopathy is feasible and preferable to plasma transfusion, if available. In nonmassive bleeding, allogeneic transfusion of blood products increases the appearance of serious adverse events and mortality and should be avoided unless clearly indicated. SUMMARY: Transfusion in trauma has to be an individual decision for a specific patient, not for a specific laboratory value. Transfusion management must aim at reducing or even avoiding the use of allogeneic blood products. This may lead to a new gold standard with cost reduction and amelioration of outcome of major trauma patients.

Does body mass index impact the early outcome of surgical revascularization? A comparison between off-pump and on-pump coronary artery bypass grafting.

OBJECTIVES: To investigate the effects of body mass index (BMI) on early outcomes after revascularization using either on-pump or off-pump surgery. METHODS: Data for 3714 of 4314 patients who underwent surgical revascularization at our institution between 1999 and 2008 were analysed. Patients were divided into two groups [off-pump coronary artery bypass (OPCAB); n = 1958 and on-pump coronary artery bypass (ONCAB); n = 1756] and further assigned into five classes according to their BMI (underweight <20 kg/m(2), normal 20-24.99 kg/m(2), overweight 25-29.99 kg/m(2), obese 30-34.99 kg/m(2) and morbidly obese ≥35 kg/m(2)). Thirty-day mortality, occurrence of major adverse cardiac events (MACEs), occurrence of major non-cardiac adverse events (MNCAEs) and length of in-hospital stay were analysed in relation to BMI only (whole cohort analysis), to BMI and chosen surgical method (ONCAB versus OPCAB) as well as confounding factors. RESULTS: In the whole cohort analysis (n = 3714), no significant differences between BMI classes could be identified with regard to 30-day mortality (P = 0.78), MACEs (P = 0.72), MNCAEs (P = 0.45) or length of in-hospital stay (P = 0.94). With increasing BMI values, 30-day mortality tended to steadily increase (1.8% in BMI class 'underweight' vs 2.6% in BMI class 'morbidly obese'; P = 0.78), whereas MNCAEs tended to decrease with an increasing BMI (17.5% in BMI class 'underweight' vs 12.2% in BMI class 'morbidly obese'; P = 0.45). Compared with ONCAB, in patients with higher BMI values, OPCAB appeared to reduce slightly the frequency of 30-day mortality, MACEs and MNCAEs, while slightly increasing the length of in-hospital stay. Adjustment for other risk factors by covariate analysis in multiple regression models did not change the inferences drawn. CONCLUSIONS: Our study did not detect significant differences between BMI classes with regard to mortality and morbidity. However, a slight trend towards a steadily increasing short-term mortality was detectable for patients with higher BMI values. When comparing ONCAB versus OPCAB, patients with higher BMI values appeared to have a weak tendency towards a reduced short-term morbidity and mortality in favour of OPCAB.

Patient blood management in orthopaedic surgery: a four-year follow-up of transfusion requirements and blood loss from 2008 to 2011 at the Balgrist University Hospital in Zurich, Switzerland.

BACKGROUND: The aim of this study was to investigate the impact of the introduction of a Patient Blood Management (PBM) programme in elective orthopaedic surgery on immediate pre-operative anaemia, red blood cell (RBC) mass loss, and transfusion. MATERIALS AND METHODS: Orthopaedic operations (hip, n=3,062; knee, n=2,953; and spine, n=2,856) performed between 2008 and 2011 were analysed. Period 1 (2008), was before the introduction of the PBM programme and period 2 (2009 to 2011) the time after its introduction. Immediate pre-operative anaemia, RBC mass loss, and transfusion rates in the two periods were compared. RESULTS: In hip surgery, the percentage of patients with immediate pre-operative anaemia decreased from 17.6% to 12.9% (p<0.001) and RBC mass loss was unchanged, being 626±434 vs 635±450 mL (p=0.974). Transfusion rate was significantly reduced from 21.8% to 15.7% (p<0.001). The number of RBC units transfused remained unchanged (p=0.761). In knee surgery the prevalence of immediate pre-operative anaemia decreased from 15.5% to 7.8% (p<0.001) and RBC mass loss reduced from 573±355 to 476±365 mL (p<0.001). The transfusion rate dropped from 19.3% to 4.9% (p<0.001). RBC transfusions decreased from 0.53±1.27 to 0.16±0.90 units (p<0.001). In spine surgery the prevalence of immediate pre-operative anaemia remained unchanged (p=0.113), RBC mass loss dropped from 551±421 to 404±337 mL (p<0.001), the transfusion rate was reduced from 18.6 to 8.6% (p<0.001) and RBC transfusions decreased from 0.66±1.80 to 0.22±0.89 units (p=0.008). DISCUSSION: Detection and treatment of pre-operative anaemia, meticulous surgical technique, optimal surgical blood-saving techniques, and standardised transfusion triggers in the context of PBM programme resulted in a lower incidence of immediate pre-operative anaemia, reduction in RBC mass loss, and a lower transfusion rate.

Applying 'Patient Blood Management' in the trauma center.

PURPOSE OF REVIEW: The purpose of this review is to highlight the use of tranexamic acid, point-of-care testing, algorithm-based treatment of trauma-associated coagulopathy with factor concentrates to reduce blood loss and transfusion requirements in order to improve outcome. In addition, the management of patients on new oral anticoagulants, drugs with renewed interest and the tolerance of relatively low hemoglobin levels in the context of trauma will be discussed. RECENT FINDINGS: Early administration of tranexamic acid reduces mortality without increasing the risk of thromboembolic events. Point-of-care testing is increasingly recommended. Goal-directed individualized coagulation algorithms with the use of factor concentrates allow reducing the amount of allogeneic blood products to be administered. Treatment of trauma patients with one of the new oral anticoagulants is challenging. Furthermore, new mechanisms have been discovered such as deep neuromuscular blockade to better tolerate acute anemia. SUMMARY: Applying Patient Blood Management concept to the trauma patient is possible and efficacious. Antihyperfibrinolytics such as tranexamic acid, point-of-care testing and coagulation algorithms with the use of factor concentrates allow a reduction of the number of transfusions, the costs and will likely ameliorate outcome of major trauma patients.

Characterization of carbon-coated magnetic nanoparticles using clinical blood coagulation assays: effect of PEG-functionalization and comparison to silica nanoparticles.

Intravascular application of magnetic nanocarriers is a critical step in the development of new therapeutic strategies, including magnetic drug targeting or hyperthermia. However, injection of particulate matter bears the intrinsic risk of contact activation of the blood coagulation cascade. In this work, we use point-of-care assays to study coagulation dynamics and clotting parameters in blood samples exposed to relevant concentrations of surface-functionalized carbon-coated iron carbide nanomagnets using unmodified nanomagnets and poly(ethylene)glycol-functionalized nanomagnets with different end-groups, including -OCH3, -NH2, -COOH, -IgG, and -ProteinA-protected-IgG (-IgG-ProtA). Silica nanoparticles with a comparable surface area are used as a reference material. For magnetic nanoparticles, we observe a decrease in clotting time by 25% compared to native blood at concentrations of 1 mg mL-1, independent of the surface functionalization, and only minor differences in receptor expression on platelets (GP-IIb-IIIa, CD62, and CD63) relative to control samples were observed. Interestingly, the inter-subject variance of the clotting time is similar to the nanoparticle-induced effect in a single subject with average clotting time. Whilst the present study is based on in vitro assays and a small group of healthy blood donors, the comparison to broadly used silica nanoparticles, and the fact that experimental intergroup variability is comparable to the observed effects from the carbon-coated nanomagnets suggests continuing investigations on their potential clinical use.

Is dilutional coagulopathy induced by different colloids reversible by replacement of fibrinogen and factor XIII concentrates?

BACKGROUND: In this in vitro trial, we assessed the effect on blood coagulation of 60% dilution with different colloids and investigated reversibility by replacement of factor XIII (F XIII), fibrinogen, and the combination of fibrinogen and F XIII. METHODS: Using the blood of 12 volunteers, the following measurements were performed at baseline and after 60% dilution with (hydroxyethyl starch solutions) HES 130/0.42, gelatin, or balanced gelatin solution: blood gas analyses, coagulation factor concentrations (F I, F II, F VII, F VIII, F XIII), impedance aggregometry (Multiplate®), and rotational thromboelastometry (ROTEM). Then F XIII and fibrinogen as well as a combination of both were added, in concentrations corresponding to 6 g fibrinogen and 1250 IU F XIII in adults. ROTEM measurements and determination of factor concentrations were again performed. RESULTS: Colloid dilution led to a significant reduction of fibrinogen polymerization, especially with HES. Platelet function was impaired by all colloids, with gelatin having a significantly greater effect (area under the curve, collagen Test, P ≤ 0.008) than HES and balanced gelatin solution. The substitution of F XIII only did not improve clot formation. Substitution of fibrinogen improved the polymerization of fibrinogen in dilutions with gelatin and balanced gelatin solution (P = 0.002), whereas HES-induced coagulopathy could not be corrected. The combination of fibrinogen and F XIII showed a better effect than the addition of fibrinogen only for certain variables. CONCLUSION: Coagulation and platelet function are impaired by all 3 colloids. However, in vitro gelatin-induced coagulopathy was significantly more reversible than HES-induced coagulopathy.

The influence of laboratory coagulation tests and clotting factor levels on Rotation Thromboelastometry (ROTEM(R)) during major surgery with hemorrhage.

BACKGROUND: The aim of this study was to determine the association between standard laboratory tests, coagulation factor concentrations, and Rotation Thromboelastometry (ROTEM® delta, TEM® International GmbH, Munich, Germany) in patients undergoing major surgery with hemorrhage. METHODS: In 45 patient's fibrinogen, factor VIII, factor XIII, International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), thrombin time, hemoglobin, leukocytes, and platelet count were simultaneously measured intraoperatively with ROTEM (EXTEM, INTEM, FIBTEM, APTEM) measurements. ROTEM parameters were: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and α-angle. Demographic and laboratory data were expressed as mean ± SD and median [range]; nonparametric Spearman rank correlations and multiple linear regressions were performed; P-values ≤0.003 were considered significant. RESULTS: Significant correlations (P ≤ 0.003) were found for CFT, α-angle, and MCF, in EXTEM, INTEM, and APTEM with platelets, INR, and fibrinogen. Factor VIII (18 measurements) showed a strong correlation (r ≥ 0.7 or r ≤ -0.7; all P ≤ 0.003) with MCF, CFT, and α-angle of EXTEM, INTEM, MCF of FIBTEM excluding CT of EXTEM, INTEM, FIBTEM and strong significant correlation for α-angle of APTEM and moderate for CFT and MCF of APTEM. A significant moderate to strong correlation of factor XIII with MCF of EXTEM, INTEM, FIBTEM, and APTEM was found. Hemoglobin was moderately correlated (r = 0.3-0.7 or r = -0.3 to -0.7) with MCF in APTEM (P = 0.003). A moderate to strong correlation of the standard coagulation tests with all ROTEM parameters was found, in particular the CT. The aPTT correlated significantly moderate to strong with CT, CFT, α-angle, and MCF of INTEM. However, multiple linear regressions were not able to show an influence of INR on ROTEM parameters except for APTEM-MCF. A significant impact of the aPTT on INTEM-CT was found. EXTEM, INTEM, and APTEM are significantly influenced by fibrinogen and platelets. CONCLUSIONS: The results confirm the clinical assumption that EXTEM, INTEM, and APTEM are associated with fibrinogen and platelets levels; INTEM-CT significantly to aPTT; and FIBTEM significantly to fibrinogen. Factor VIII showed a significant correlation with all ROTEM parameters except CT of EXTEM, INTEM, FIBTEM, and CFT and MCF of APTEM.