Host cell protein networks as a novel co-elution mechanism during protein A chromatography.

Host cell proteins (HCPs) are process-related impurities of therapeutic proteins produced in for example, Chinese hamster ovary (CHO) cells. Protein A affinity chromatography is the initial capture step to purify monoclonal antibodies or Fc-based proteins and is most effective for HCP removal. Previously proposed mechanisms that contribute to co-purification of HCPs with the therapeutic protein are either HCP-drug association or leaching from chromatin heteroaggregates. In this study, we analyzed protein A eluates of 23 Fc-based proteins by LC-MS/MS to determine their HCP content. The analysis revealed a high degree of heterogeneity in the number of HCPs identified in the different protein A eluates. Among all identified HCPs, the majority co-eluted with less than three Fc-based proteins indicating a drug-specific co-purification for most HCPs. Only ten HCPs co-purified with over 50% of the 23 Fc-based proteins. A correlation analysis of HCPs identified across multiple protein A eluates revealed their co-elution as HCP groups. Functional annotation and protein interaction analysis confirmed that some HCP groups are associated with protein-protein interaction networks. Here, we propose an additional mechanism for HCP co-elution involving protein-protein interactions within functional networks. Our findings may help to guide cell line development and to refine downstream purification strategies.

Surgery Within 24 Hours Reduces Mortality and General Complication Rates in Patients Who Have Periprosthetic Femoral Fractures at the Hip.

BACKGROUND: In patients who have hip fractures, treatment within 24 hours reduces mortality and complication rates. A similar relationship can be assumed for patients who have hip periprosthetic femoral fractures (PPFs) owing to the similar baseline characteristics of the patient populations. This monocentric retrospective study aimed to compare the complication and mortality rates in patients who had hip PPF treated within and after 24 hours. METHODS: In total, 350 consecutive patients who had hip PPF in a maximum-care arthroplasty and trauma center between 2006 and 2020 were retrospectively evaluated. The cases were divided into 2 groups using a time to surgery (TTS) of 24 hours as the cutoff value. The primary outcome variables were operative and general complications as well as mortalities within 1 year. RESULTS: Overall, the mean TTS was 1.4 days, and the 1-year mortality was 14.6%. The TTS ≤ 24 hours (n = 166) and TTS > 24 hours (n = 184) groups were comparable in terms of baseline characteristics and comorbidities. Surgical complications were equally frequent in the 2 groups (16.3 versus 15.2%, P = .883). General complications occurred significantly more often in the late patient care group (11.4 versus 28.3%, P < .001). In addition, the 30-day mortality (0.6 versus 5.5%, P = .012), and 1-year mortality (8.3 versus 20.5%, P = .003) rates significantly increased in patients who had TTS > 24 hours. Cox regression analysis yielded a hazard ratio of 4.385 (P < .001) for the TTS > 24 hours group. CONCLUSIONS: Prompt treatment is required for patients who have hip PPF to reduce mortality and overall complications.

Highland games: A benchmarking exercise in predicting biophysical and drug properties of monoclonal antibodies from amino acid sequences.

Biopharmaceutical product and process development do not yet take advantage of predictive computational modeling to nearly the degree seen in industries based on smaller molecules. To assess and advance progress in this area, spirited coopetition (mutually beneficial collaboration between competitors) was successfully used to motivate industrial scientists to develop, share, and compare data and methods which would normally have remained confidential. The first "Highland Games" competition was held in conjunction with the October 2018 Recovery of Biological Products Conference in Ashville, NC, with the goal of benchmarking and assessment of the ability to predict development-related properties of six antibodies from their amino acid sequences alone. Predictions included purification-influencing properties such as isoelectric point and protein A elution pH, and biophysical properties such as stability and viscosity at very high concentrations. Essential contributions were made by a large variety of individuals, including companies which consented to provide antibody amino acid sequences and test materials, volunteers who undertook the preparation and experimental characterization of these materials, and prediction teams who attempted to predict antibody properties from sequence alone. Best practices were identified and shared, and areas in which the community excels at making predictions were identified, as well as areas presenting opportunities for considerable improvement. Predictions of isoelectric point and protein A elution pH were especially good with all-prediction average errors of 0.2 and 1.6 pH unit, respectively, while predictions of some other properties were notably less good. This manuscript presents the events, methods, and results of the competition, and can serve as a tutorial and as a reference for in-house benchmarking by others. Organizations vary in their policies concerning disclosure of methods, but most managements were very cooperative with the Highland Games exercise, and considerable insight into common and best practices is available from the contributed methods. The accumulated data set will serve as a benchmarking tool for further development of in silico prediction tools.

Systematic Investigation of Insulin Fibrillation on a Chip.

A microfluidic protein aggregation device (microPAD) that allows the user to perform a series of protein incubations with various concentrations of two reagents is demonstrated. The microfluidic device consists of 64 incubation chambers to perform individual incubations of the protein at 64 specific conditions. Parallel processes of metering reagents, stepwise concentration gradient generation, and mixing are achieved simultaneously by pneumatic valves. Fibrillation of bovine insulin was selected to test the device. The effect of insulin and sodium chloride (NaCl) concentration on the formation of fibrillar structures was studied by observing the growth rate of partially folded protein, using the fluorescent marker Thioflavin-T. Moreover, dual gradients of different NaCl and hydrochloric acid (HCl) concentrations were formed, to investigate their interactive roles in the formation of insulin fibrils and spherulites. The chip-system provides a bird's eye view on protein aggregation, including an overview of the factors that affect the process and their interactions. This microfluidic platform is potentially useful for rapid analysis of the fibrillation of proteins associated with many misfolding-based diseases, such as quantitative and qualitative studies on amyloid growth.

[Effectiveness of blood flow restriction training in competitive sports]. / Effektivität des "blood flow restriction training" im Leistungssport.

BACKGROUND: Training under conditions of blood flow restriction (BFR) has recently been advocated as an option for alternative training in athletes. OBJECTIVE: Does BFR make sense in athlete training? MATERIAL AND METHODS: An overview of the currently available literature is given. RESULTS: The use of BFR appears to be a possibility to achieve muscle hypertrophy and an increase in muscular strength and can also improve parameters of cardiocirculatory function. CONCLUSION: Various approaches for implementation of BFR in athletes can be found in the literature. These approaches differ in the frequency, force used, duration and finally type of implementation of BFR itself. Clear recommendations for training cannot be given to date and the individual weighing up of possibilities and supervised implementation of BFR in athlete training by the trainer are still necessary.

Long-term outcome after surgical treatment of intra-articular tibial plateau fractures in skiers.

INTRODUCTION: Tibial plateau fractures occur frequently during downhill skiing. There is a lack of information about the outcome and development of posttraumatic osteoarthritis after internal fixation of such fractures at long-term follow-up in skiers. MATERIALS AND METHODS: A population of 83 skiers was followed up in a case series after internal fixation of intra-articular tibial plateau fractures AO-OTA 41 B1-B3 and C1-C3. Functional outcomes Visual Analog Scale, Tegner Activity Scale, Modified Lysholm Score, Hospital for Special Surgery (HSS) Knee Score and X-ray images of the affected knees (preoperative, postoperative and at time of follow-up) were obtained. Radiological evaluation focused on severity of osteoarthritis according to the Kellgren and Lawrence score of the lateral, medial and retropatellar knee compartments separately. Subgroup analyses for fracture type and age were performed separately. RESULTS: Patients age was 49.8 ± 12.9 years (range 19-74 years) at the time of surgery, with a mean follow-up period of 10.3 ± 1.9 years (range 6-14 years). All tibial plateau fractures affected the lateral compartment, while the medial compartment was affected in addition as part of bicondylar fractures in two cases. Both the Tegener Activity Scale and Lysholm Score decreased significantly during the follow-up period and their median values dropped from 6 (range 3-7) to 5 (range 2-7) and from 100 (range 90-100) to 95 (range 58-100), respectively (both p < .01). The median clinical knee function at the time of follow-up revealed an HSS Knee Score of 96.5 points (range 74-100). Among the whole patient population, the radiological evaluation at follow-up revealed a significantly higher grade of osteoarthritis in all compartments of the knee joint compared to the time of the operation (p < .01). The grade of osteoarthritis in the lateral compartment was significantly higher than that in the medial and retropatellar compartments (p < .01). CONCLUSIONS: In addition to physiologic aging, progression of radiologic signs of osteoarthritis following internal fixation of intra-articular tibial plateau fractures in an athletic population of skiers is most severe in the lateral knee compartment corresponding to fracture location. However, the long-term functional outcomes seem to be very satisfactory.

[Isolated fracture of the coracoid process in a 14-year-old national water polo player : Case example]. / Isolierte Fraktur des Processus coracoideus bei einem 14-jährigen Wasserballnationalspieler : Fallbeispiel.

BACKGROUND: Isolated fractures of the coracoid process during sporting activities are very rare. There are a few case studies and retrospective studies with low numbers of cases. OBJECTIVE: Presentation of an initially neglected fracture and conservative treatment. METHODS: Case study of a 14-year-old national water polo player with a non-dislocated fracture of the coracoid process and conservative therapy using focused shockwave therapy. RESULT: Return to sports after conservative therapy was after 13 weeks and return to competitive sport after 14 weeks. CONCLUSION: In cases with therapy refractory shoulder pain after trauma and unremarkable native X­ray, extended 3D imaging by magnetic resonance imaging (MRI) or computed tomography (CT) should be done early. Conservative therapy of a non-dislocated fracture in this case showed a good outcome.

A microfluidic chip with a staircase pH gradient generator, a packed column and a fraction collector for chromatofocusing of proteins.

A microfluidic device for pH gradient chromatofocusing is presented, which performs creation of a micro-column, pH gradient generation, and fraction collection in a single device. Using a sieve micro-valve, anion exchange particles were packed into a microchannel in order to realize a solid-phase absorption column. To fractionate proteins according to their isoelectric points, elution buffer solutions with a stepwise pH gradient were prepared in 16 parallel mixing reactors and flowed through the micro-column, wherein a protein mixture was previously loaded. The volume of the column is only 20 nL, hence it allows extremely low sample consumption and fast analysis compared with a conventional system. We demonstrated separation of two proteins, albumin-fluorescein isothiocyanate conjugate (FITC-BSA) and R-Phycoerythrin (R-PE), by using a microcolumn of commercial charged polymeric particles (Source 15Q). The microfluidic device can be used as a rapid diagnostic tool to analyse crude mixtures of proteins or nucleic acids and determine adsorption/desorption characteristics of various biochemical products, which can be helpful for scientific fundamental understanding as well as instrumental in various industrial applications, especially in early stage screening and process development.

A microfluidic device for the batch adsorption of a protein on adsorbent particles.

A microfluidic platform or "microfluidic batch adsorption device" is presented, which performs two sets of 9 parallel protein incubations with/without adsorbent particles to achieve an adsorption isotherm of a protein in a single experiment. The stepwise concentration gradient of a target protein was created by the integration of microvalves into the device. The nanoliter-scale reactor (41 nl) allows about 5000 times reduction of sample consumption and fast analysis compared with a conventional 96 well plate. The integration of two sets of parallel reactors as reference reactors and adsorption reactors, respectively, in a single microfluidic format has many advantages, such as the exclusion of the influence of undesired experimental fluctuations, and the possibility of real-time tracing of adsorption processes. We performed batch adsorption of albumin-fluorescein isothiocyanate conjugate (FITC-BSA) on polymeric particles (Source 15Q) to obtain an adsorption isotherm. The obtained on-chip parameters maximum adsorption amount (Qmax) and adsorption constant (Keq) were 0.33 ± 0.03 ng per particle and 0.97 ± 0.22 L g-1, respectively, which are in good agreement with off-chip values (Qmax = 0.34 ± 0.01 ng per particle and Keq = 0.81 ± 0.10 L g-1). On-chip adsorption isotherms of FITC-BSA at various concentrations of sodium chloride (NaCl) were measured to evaluate the effect of this salt on the adsorption capability of Source 15Q. The microfluidic device serves as a new analytical tool, useful in biotechnological and industrial applications, where the adsorption behavior of (bio)molecules on commercial adsorbent particles plays critical roles, such as protein separation and purification, detection of analytes and biomarkers, and solid-phase immunoassays.

Point-of-care monitoring for the management of trauma-induced bleeding.

PURPOSE OF REVIEW: Knowledge of trauma-induced coagulopathy has been grown in the past and point-of-care suitable devices for coagulation testing have been introduced. Methodology and clinical application of different systems for point-of-care coagulation monitoring are shown with a focus on thrombelastography as measured by TEG, rotational thromboelastometry as measured by ROTEM and impedance aggregometry as measured by the multiplate analyser and ROTEM platelet. RECENT FINDINGS: Two different methods for point-of-care coagulation assessment are available: viscoelastic tests (ROTEM, TEG) and impedance aggregometry. In different settings these methods have been evaluated in various publications pointing out the possibility of reducing transfusion requirements, transfusion-related side effects, and resulting costs. SUMMARY: Point-of-care assessment of coagulation in trauma patients appears to be at least promising. However, because published data mostly are of retrospective or observational nature only, there is a need for prospective, randomized and controlled studies.

Cost-Effectiveness of POC Coagulation Testing Using Multiple Electrode Aggregometry.

BACKGROUND: The economic effects of Point-of-Care (POC) coagulation testing including Multiple Electrode Aggregometry (MEA) with the Multiplate device have not been examined. METHODS: A health economic model with associated clinical endpoints was developed to calculate the effectiveness and estimated costs of coagulation analyses based on standard laboratory testing (SLT) or POC testing offering the possibility to assess platelet dysfunction using aggregometric measures. Cost estimates included pre- and perioperative costs of hemotherapy, intra- and post-operative coagulation testing costs, and hospitalization costs, including the costs of transfusion-related complications. RESULTS: Our model calculation using a simulated true-to-life cohort of 10,000 cardiac surgery patients assigned to each testing alternative demonstrated that there were 950 fewer patients in the POC branch who required any transfusion of red blood cells. The subsequent numbers of massive transfusions and patients with transfusion-related complications were reduced with the POC testing by 284 and 126, respectively. The average expected total cost in the POC branch was 288 Euro lower for every treated patient than that in the SLT branch. CONCLUSIONS: Incorporating aggregometric analyses using MEA into hemotherapy algorithms improved medical outcomes in cardiac surgery patients in the presented health economic model. There was an overall better economic outcome associated with POC testing compared with SLT testing despite the higher costs of testing.

Multiple electrode aggregometry for the assessment of acquired platelet dysfunctions during extracorporeal circulation.

BACKGROUND: There have been many reports on how the usage of extracorporeal circulation (ECC) is independently associated with the induction of platelet dysfunctions. The aim of the present investigation was to study the capability of the multiple electrode aggregometry (MEA) using the Multiplate (Roche AG, Grenzach, Germany) device to reflect the extent of ECC-associated platelet dysfunctions. PATIENTS AND METHODS: The study population consisted of patients who were treated with either hypothermic (cardiopulmonary bypass [CPB]) or normothermic (extracorporeal membrane oxygenation) ECC. Hemostatic analyses included conventional laboratory coagulation tests and aggregometric measures following stimulation with different agonists using MEA. The area under the aggregation curve in the ADPtest (ex vivo adenosine diphosphate induced platelet aggregation) of the MEA was defined as the primary end point. The analyses were performed before the usage of ECC (baseline) and 90 minutes (T1), 120 minutes (T2), 150 minutes (T3), and 180 minutes (T4) after the usage of ECC. In the hypothermic ECC group, additional hemostatic analyses were performed after the patient's postoperative admission to the intensive care unit (T5). Periprocedural data and results of other hemostatic testing were defined as secondary end points. RESULTS: A total of n = 40 patients were assessed for eligibility and n = 25 patients were finally enrolled into the study (hypothermic ECC group: n = 20; normothermic ECC group: n = 5). The extent of ADP-induced platelet aggregation decreased significantly between baseline and consecutive measuring points during hypothermic ECC and remained unchanged between T4 and T5. In the normothermic ECC group, ADP-induced aggregability was significantly lower at T1 compared with baseline and remained unchanged from T1 onward. CONCLUSION: Data from the present study indicate that ex vivo ADP-induced platelet aggregation in MEA reflects the time-dependent extent of ECC-induced platelet dysfunction.

Aggregometric assessment of clonidine's impact on the efficacy of dual platelet inhibition.

BACKGROUND: Clonidine is commonly used as a calmative and antihypertensive agent in perioperative care. Due to the drug's alpha-2-agonistic effects, it has recently been hypothesised that clonidine may affect platelet aggregability. The present investigation aimed to study the potential impact of clonidine on the efficacy of dual antiplatelet therapy. METHODS: In this prospective, observational, single-centre study, patients treated with dual antiplatelet therapy were screened for eligibility. The patients were enrolled in the study if ex vivo thrombin-induced (TRAPtest), arachidonic acid-induced (ASPItest) and adenosine diphosphate-induced (ADPtest) platelet aggregation, as measured using multiple electrode aggregometry (MEA; Multiplate, Roche AG, Grenzach, Germany), confirmed efficient dual platelet inhibition. Ex vivo induced platelet aggregation was assessed before (baseline) and 3 minutes after (T1) spiking blood samples with either 1 ng/mL clonidine or sodium chloride 0.9% (control group). RESULTS: In total, 34 patients were finally enrolled in the study. Compared with baseline, platelet aggregation in the ASPItest and ADPtest was significantly increased at T1 in both groups. Platelet aggregation in the TRAPtest remained unchanged between baseline and T1 in both groups. Comparing platelet aggregation at T1, we detected no differences between blood samples that were spiked with clonidine and blood samples that were spiked with sodium chloride 0.9% in the TRAPtest, the ASPItest, or the ADPtest. CONCLUSIONS: The results of this study indicate that clonidine does not affect platelet aggregability in patients treated with dual antiplatelet therapy. The findings of the study also indicate that ex vivo induced platelet aggregation in the ASPItest and ADPtest increases with the duration between blood drawing and MEA analyses.

Therapy aspects of peri-implant femoral fractures-a retrospective analysis of 64 patients.

PURPOSE: The incidence of peri-implant femoral fractures (PIFF) is increasing. Information regarding outcomes, timing of surgery, risk factors, and a clinically applicable treatment algorithm are lacking. The aim of this study was to identify outcome-related risk factors and to derive a treatment algorithm. METHODS: Sixty-four PIFFs treated between 01.01.2006 and 31.12.2020 in a level I trauma centre were evaluated retrospectively for fracture pattern, surgical technique, risk factors, complications, and 1-year mortality. The study was approved by the ethics committee (No. 21-2714-104). RESULTS: One-year mortality was 24.1%. Surgical complications occurred in 4.7%, and general complications in 15.6% of the patients. General complications, low haemoglobin level at admission, elevated CHA2DS2-VASc, and Charlson score resulted in increased 1-year mortality. Time to surgery > 24 h did not increase complication or mortality rates. The three predominant fracture patterns were fractures close or distal to cephalomedullary nails, close or proximal to distal lateral plates, and close or distal to sliding hip screws. Recommendations for surgical treatment were derived: Osteosynthesis should enable as much weight-bearing as possible; the initial implant should only be removed, if this is essential for the new osteosynthesis; lateral locking plates should span the whole femur; antegrade nails should have a cephalomedullary component to avoid consecutive femoral neck fractures; implants should overlap to reduce the risk of consecutive inter-implant fractures. CONCLUSION: Risk factors for 1-year mortality in patients with PIFFs were identified. A treatment algorithm and general principles for surgery of PIFFs were developed.

Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial.

BACKGROUND: Fibrinogen is suggested to play an important role in managing major bleeding. However, clinical evidence regarding the effect of fibrinogen concentrate (derived from human plasma) on transfusion is limited. The authors assessed whether fibrinogen concentrate can reduce blood transfusion when given as intraoperative, targeted, first-line hemostatic therapy in bleeding patients undergoing aortic replacement surgery. METHODS: In this single-center, prospective, placebo-controlled, double-blind study, patients aged 18 yr or older undergoing elective thoracic or thoracoabdominal aortic replacement surgery involving cardiopulmonary bypass were randomized to fibrinogen concentrate or placebo, administered intraoperatively. Study medication was given if patients had clinically relevant coagulopathic bleeding immediately after removal from cardiopulmonary bypass and completion of surgical hemostasis. Dosing was individualized using the fibrin-based thromboelastometry test. If bleeding continued, a standardized transfusion protocol was followed. RESULTS: Twenty-nine patients in the fibrinogen concentrate group and 32 patients in the placebo group were eligible for the efficacy analysis. During the first 24 h after the administration of study medication, patients in the fibrinogen concentrate group received fewer allogeneic blood components than did patients in the placebo group (median, 2 vs. 13 U; P < 0.001; primary endpoint). Total avoidance of transfusion was achieved in 13 (45%) of 29 patients in the fibrinogen concentrate group, whereas 32 (100%) of 32 patients in the placebo group received transfusion (P < 0.001). There was no observed safety concern with using fibrinogen concentrate during aortic surgery. CONCLUSIONS: Hemostatic therapy with fibrinogen concentrate in patients undergoing aortic surgery significantly reduced the transfusion of allogeneic blood products. Larger multicenter studies are necessary to confirm the role of fibrinogen concentrate in the management of perioperative bleeding in patients with life-threatening coagulopathy.

Management of hemorrhage in cardiothoracic surgery.

Bleeding is an important issue in cardiothoracic surgery, and about 20% of all blood products are transfused in this clinical setting worldwide. Transfusion practices, however, are highly variable among different hospitals and more than 25% of allogeneic blood transfusions have been considered inappropriate. Furthermore, both bleeding and allogeneic blood transfusion are associated with increased morbidity, mortality, and hospital costs. In the past decades, several attempts have been made to find a universal hemostatic agent to ensure hemostasis during and after cardiothoracic surgery. Most drugs studied in this context have either failed to reduce bleeding and transfusion requirements or were associated with severe adverse events, such as acute renal failure or thrombotic/thromboembolic events and, in some cases, increased mortality. Therefore, an individualized goal-directed hemostatic therapy ("theranostic" approach) seems to be more appropriate to stop bleeding in this complex clinical setting. The use of point-of-care (POC) transfusion and coagulation management algorithms guided by viscoelastic tests such as thromboelastometry/thromboelastography in combination with POC platelet function tests such as whole blood impedance aggregometry, and based on first-line therapy with fibrinogen and prothrombin complex concentrate have been associated with reduced allogeneic blood transfusion requirements, reduced incidence of thrombotic/thromboembolic and transfusion-related adverse events, and improved outcomes in cardiac surgery. This article reviews the current literature dealing with the management of hemorrhage in cardiothoracic surgery based on POC diagnostics and with specific coagulation factor concentrates and its impact on transfusion requirements and patients' outcomes.

Potential value of transfusion protocols in cardiac surgery.

PURPOSE OF REVIEW: On the one hand, cardiac and aortic surgery is associated with a high rate of allogeneic blood transfusion. On the other hand, both bleeding and allogeneic blood transfusion is associated with increased morbidity, mortality, and hospital costs in cardiac and aortic surgery. This article reviews the current literature between 1995 and 2012 dealing with transfusion protocols in cardiovascular surgery. The 16 studies fitting these search criteria have evaluated the impact of the implementation of ROTEM/TEG based coagulation management algorithms on transfusion requirement and outcome in overall 8507 cardiovascular surgical patients. RECENT FINDINGS: The use of point-of-care (POC) transfusion and coagulation management algorithms based on viscoelastic tests such as thromboelastometry (ROTEM) and thrombelastography (TEG) in combination with POC platelet function tests such as whole blood impedance aggregometry (Multiplate) have been shown to be associated with reduced allogeneic blood transfusion requirements, reduced incidence of thrombotic/thromboembolic and transfusion-related adverse events, and improved outcomes in cardiac surgery. SUMMARY: Implementation of POC algorithms including a comprehensive bundle of POC diagnostics (thromboelastometry and whole blood impedance aggregometry) in combination with first-line therapy using immediately available specific coagulation factor concentrates (fibrinogen and prothrombin complex concentrate) and defining strict indications, calculated dosages, and clear sequences for each haemostatic intervention seems to be complex but most effective in reducing perioperative transfusion requirements and has been shown to be associated with a decreased incidence of thrombotic/thromboembolic events, transfusion-related adverse events, as well as with improved patients' outcomes including 6-month mortality.

[Emergency kits in dental practice. A model, which could improve care]. / Die Notfallausstattung in der zahnärztlichen Praxis. Ein Modell, wie es vielleicht besser klappen kann.

INTRODUCTION: Even if a mortal incident occurs rarely in a dentists daily routine there is a chance of it. The entire team has to face a great challenge then. Stress and incertainty are leading to mistakes and cost precious time which is not given for treating due to emergency. MATERIAL: Usual emergencies helped developing emergency kits which should make it easy for the practise team to act right and aim orientated in case of emergency. Therefore the combination for an as much efficient as possible state of those kits has priority. Through these the acting procedures turn out easier and more secure. RESULT: The management in case of emergency could be highly improved through the developing of emergency kits. The acting procedures turn out easier and more secure. The possibility for mistakes decreases.

Haemostatic therapy in coronary artery bypass graft patients with decreased platelet function: comparison of fibrinogen concentrate with allogeneic blood products.

BACKGROUND: Patients undergoing coronary artery bypass grafting (CABG) are at risk of postoperative bleeding because of decreased platelet function and cardiopulmonary bypass (CPB)-induced haemostatic impairment. Fibrinogen concentration decreases by 34-42% of the preoperative level by the end of CPB. An inverse relationship between perioperative plasma fibrinogen levels and postoperative bleeding has been reported in CABG patients. Administration of fibrinogen concentrate after weaning from CPB in patients with diffuse microvascular bleeding may help promote haemostasis. We compared patient outcomes following fibrinogen concentrate administration or transfusion of allogeneics in CABG patients with decreased platelet function. METHODS: Thirty-eight patients with decreased preoperative platelet function in Multiplate aggregometry were included. Patients with bleeding after CPB received either fibrinogen concentrate (guided by the measurement of fibrin clot quality using the FIBTEM thromboelastometric test) or allogeneics. RESULTS: Twenty-nine of 38 patients received haemostatic therapy (bleeding + fibrinogen group, n = 10; bleeding + allogeneics group, n = 19). Total transfusion (median (interquartile range)) was significantly lower in the bleeding + fibrinogen group (0 (0, 3.8) units), compared with the bleeding + allogeneics group (6 (5, 8) units, p = 0.0073). Bolus administration of fibrinogen concentrate increased FIBTEM maximum clot firmness from 10.5 (9.3, 11) mm after CPB to 20.5 (20, 21.8) mm at the end of surgery. Postoperative outcomes were similar in both groups. No treatment-related complications were observed after fibrinogen concentrate. CONCLUSIONS: In CABG patients with bleeding after CPB, FIBTEM-guided administration of fibrinogen concentrate resulted in overall decreased transfusion, compared with haemostatic therapy with allogeneics. Fibrinogen concentrate administration increased the fibrin clot quality and helped achieve haemostasis.

Isovolaemic hemodilution with gelatin and hydroxyethylstarch 130/0.42: effects on hemostasis in piglets.

OBJECTIVES: Artificial colloids, frequently used to prevent hemorrhagic shock in children, impair blood coagulation. To determine the impact of acute isovolaemic hemodilution with artificial colloids on clot formation, we conducted an experimental study in a pediatric animal model. METHODS: Fifteen piglets underwent hemorrhage by withdrawing 40 ml·kg(-1) of blood volume in steps of 10 ml·kg(-1) each within 1 hour. After each withdrawal, the blood loss was randomly compensated by administering 4% gelatin (GEL) or hydroxylethyl starch 130/0.42 (HES) in a ratio of 1 : 1, or isotonic crystalloid solution (ICS) in a ratio of 1 : 4 for isovolaemic hemodilution. Quality of clot formation and platelet function was measured using Thrombelastometry (ROTEM(®)) and Multiple electrode impedance aggregometry (Multiplate(®)) after 10, 20, and 40 ml·kg(-1) blood replacement. RESULTS: Moderate hemodilution (10-20 ml·kg(-1) blood replacement) caused no significant differences among groups (e.g. INTEM(®)-MCF after 20 ml·kg(-1) blood replacement (ICS vs GEL vs HES, P > 0.05). Profound hemodilution with 40 ml·kg(-1) blood replacement showed a significant difference between ICS and both colloids (P < 0.05), but no significant differences between GEL and HES. CONCLUSIONS: Impairment of clot formation by moderate isovolaemic hemodilution did not significantly differ between ICS, GEL, and HES. Profound hemodilution of more than 50% of the estimated blood volume with GEL and HES caused significant impairment of clot formation in comparison to ICS and has to be considered when using high amounts of these synthetic colloids.