The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60-70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.

Simplified treatment algorithm for the management of trauma-induced hemorrhage without viscoelastic testing.

Uncontrolled bleeding after major trauma remains a significant cause of death, with up to a third of trauma patients presenting with signs of coagulopathy at hospital admission. Rapid correction of coagulopathy is therefore vital to improve mortality rates and patient outcomes in this population. Early and repeated monitoring of coagulation parameters followed by clear protocols to correct hemostasis is the recommended standard of care for bleeding trauma patients. However, although a number of treatment algorithms are available, these are frequently complex and can rely on the use of viscoelastic testing, which is not available in all treatment centers. We therefore set out to develop a concise and pragmatic algorithm to guide treatment of bleeding trauma patients without the use of point-of-care viscoelastic testing. The algorithm we present here is based on published guidelines and research, includes recommendations regarding treatment and dosing, and is simple and clear enough for even an inexperienced physician to follow. In this way, we have demonstrated that treatment protocols can be developed and adapted to the resources available, to offer clear and relevant guidance to the entire trauma team.

A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations.

The novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (COVID-19). To develop human neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor-binding domain (RBD) of the spike protein were selected by phage display. The antibody STE90-C11 shows a subnanometer IC50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody is demonstrated in the Syrian hamster and in the human angiotensin-converting enzyme 2 (hACE2) mice model. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD is solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibition of STE90-C11 is not blocked by many known emerging RBD mutations. STE90-C11-derived human IgG1 with FcγR-silenced Fc (COR-101) is undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.

Mild Acquired Factor XIII Deficiency and Clinical Relevance at the ICU-A Retrospective Analysis.

Acquired FXIII deficiency is a relevant complication in the perioperative setting; however, we still have little evidence about the incidence and management of this rarely isolated coagulopathy. This study aims to help find the right value for the substitution of patients with an acquired mild FXIII deficiency. In this retrospective single-center cohort study, we enrolled critically ill patients with mild acquired FXIII deficiency (>5% and ≤70%) and compared clinical and laboratory parameters, as well as pro-coagulatory treatments. The results of the present analysis of 104 patients support the clinical relevance of FXIII activity out of the normal range. Patients with lower FXIII levels, beginning at <60%, had lower minimum and maximum hemoglobin values, corresponding to the finding that patients with a minimum FXIII activity of <50% needed significantly more packed red blood cells. FXIII activity correlated significantly with general coagulation markers such as prothrombin time, activated partial thromboplastin time, and fibrinogen. Nevertheless, comparing the groups with a cut-off of 50%, the amount of fresh frozen plasma, thrombocytes, PPSB, AT-III, and fibrinogen given did not differ. These results indicate that a mild FXIII deficiency occurring at any point of intensive care unit stay is also probably relevant for the total need of packed red blood cells, independent of pro-coagulatory management. In alignment with the ESAIC guidelines, the measurement of FXIII in critically ill patients with the risk of bleeding and early management, with the substitution of FXIII at levels <50%-60%, could be suggested.

Management of Coagulopathy in Bleeding Patients.

Early recognition of coagulopathy is necessary for its prompt correction and successful management. Novel approaches, such as point-of-care testing (POC) and administration of coagulation factor concentrates (CFCs), aim to tailor the haemostatic therapy to each patient and thus reduce the risks of over- or under-transfusion. CFCs are an effective alternative to ratio-based transfusion therapies for the correction of different types of coagulopathies. In case of major bleeding or urgent surgery in patients treated with vitamin K antagonist anticoagulants, prothrombin complex concentrate (PCC) can effectively reverse the effects of the anticoagulant drug. Evidence for PCC effectiveness in the treatment of direct oral anticoagulants-associated bleeding is also increasing and PCC is recommended in guidelines as an alternative to specific reversal agents. In trauma-induced coagulopathy, fibrinogen concentrate is the preferred first-line treatment for hypofibrinogenaemia. Goal-directed coagulation management algorithms based on POC results provide guidance on how to adjust the treatment to the needs of the patient. When POC is not available, concentrate-based management can be guided by other parameters, such as blood gas analysis, thus providing an important alternative. Overall, tailored haemostatic therapies offer a more targeted approach to increase the concentration of coagulation factors in bleeding patients than traditional transfusion protocols.

Training to identify red flags in the acute care of trauma: who are the patients at risk for early death despite a relatively good prognosis? An analysis from the TraumaRegister DGU®.

BACKGROUND: In the acute care of trauma, some patients with a low estimated risk of death die suddenly and unexpectedly. In this study, we aim to identify predictors for early death within 24 h following hospital admission in low-risk patients. METHODS: The TraumaRegister DGU® was used to collect records of patients who were primarily treated in a participating hospital between 2004 and 2013 with a RISC II score below 10%. RESULTS: During the study period, 64,379 patients met the inclusion criteria. The mean RISC II score was 2.0%, and the mean ISS was 16 ± 9. The overall hospital mortality rate was 2.1%, and 0.5% of patients (n = 301) died within the first 24 h. A SPB of ≤ 90 mmHg was associated with an increased risk of death (p < 0.001). An AIS abdomen score of ≥ 3 was associated with increased risk of death within the first 24 h (p < 0.001). A high risk of early death was also seen in patients with an AIS score (thorax) ≥ 3; 51% of those who died died within the first 24 h (p < 0.005). Death in patients over 60 years was more common after 24 h (p < 0.001). Patients with an ASA score of ≥ 3 were more likely to die after the first 24 h (p < 0.001). CONCLUSIONS: Indicators predicting a high risk of early death in patients with a low RISC II score include a SPB ≤ 90 mmHg and severe chest and abdominal trauma. Emergency teams involved in the acute care of trauma patients should be aware of these "red flags" and treat their patients accordingly.

[Perioperative management of patients equipped with cardiac implanted electronic devices]. / Patienten mit implantierten Schrittmachern und†/†oder Defibrillatoren - Perioperatives Vorgehen.

Anaesthetists are in increasing frequency confronted with patients equipped with cardiac implantable electrical devices. A consensus conference standardized the handling of such patients for elective cases. However, this multidisciplinary approach is characterized by a complexity, which is hard to handle in emergency cases and even in nowadays clinical routine. However, risks associated with electrocautery or electromagnetic interference can be easily handled applying a significantly easier approach. Telemetric reprogramming and/or postoperative interrogation of the cardiac implanted eletronical device can be avoided in most cases.

Severe sepsis and septic shock in pre-hospital emergency medicine: survey results of medical directors of emergency medical services concerning antibiotics, blood cultures and algorithms.

Delayed antibiotic treatment for patients in severe sepsis and septic shock decreases the probability of survival. In this survey, medical directors of different emergency medical services (EMS) in Germany were asked if they are prepared for pre-hospital sepsis therapy with antibiotics or special algorithms to evaluate the individual preparations of the different rescue areas for the treatment of patients with this infectious disease. The objective of the survey was to obtain a general picture of the current status of the EMS with respect to rapid antibiotic treatment for sepsis. A total of 166 medical directors were invited to complete a short survey on behalf of the different rescue service districts in Germany via an electronic cover letter. Of the rescue districts, 25.6 % (n = 20) stated that they keep antibiotics on EMS vehicles. In addition, 2.6 % carry blood cultures on the vehicles. The most common antibiotic is ceftriaxone (third generation cephalosporin). In total, 8 (10.3 %) rescue districts use an algorithm for patients with sepsis, severe sepsis or septic shock. Although the German EMS is an emergency physician-based rescue system, special opportunities in the form of antibiotics on emergency physician vehicles are missing. Simultaneously, only 10.3 % of the rescue districts use a special algorithm for sepsis therapy. Sepsis, severe sepsis and septic shock do not appear to be prioritized as highly as these deadly diseases should be in the pre-hospital setting.