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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.

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.

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.

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.

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.

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.

The novel betacoranavirus SARS-CoV-2 causes a form of severe pneumonia disease, termed COVID-19 (coronavirus disease 2019). Recombinant human antibodies are proven potent neutralizers of viruses and can block the interaction of viral surface proteins with their host receptors. To develop 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 S1 subunit of the viral spike (S) protein were selected by phage display. The selected antibodies were produced in the scFv-Fc format and 30 showed more than 80% inhibition of spike (S1-S2) binding to cells expressing ACE2, assessed by flow cytometry screening assay. The majority of these inhibiting antibodies are derived from the VH3-66 V-gene. The antibody STE90-C11 showed a sub nM IC50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody was demonstrated in the Syrian hamster and in the hACE2 mice model using a silenced human IgG1 Fc part. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD was solved at 2.0 Angstrom resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibtion of STE90-C11 is not blocked by many known RBD mutations including N439K, L452R, E484K or L452R+E484Q (emerging B.1.617). STE90-C11 derived human IgG1 with Fc-gamma receptor silenced Fc (COR-101) is currently undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19. Competing Interest Statement The authors declare a conflict of interest. F.B., D.M., N.L., S.S., P.A.H., R.B., M.R., K.T.S., K.D.R.R., S.Z.-E., M.B., V.F., S.T., M.S. and M.H. are inventors on a patent application on blocking antibodies against SARS-CoV-2. A.H., A.F. and T.S. are officers of CORAT Therapeutics GmbH, a company founded by YUMAB GmbH for the clinical and regulatory development of STE90-C11 (development name COR-101) (ClinicalTrials.gov ID: NCT04674566 for safety and efficacy of COR-101 in hospitalized patients with moderate to severe COVID-19). A.H. is shareholder of CORAT Therapeutics GmbH. S.D. and M.H. are advisors of Corat Therapeutics GmbH. A.F., T.S., S.D. and M.H. are shareholders of YUMAB GmbH. Footnotes * The highlights of the revised version are: - binding and inhibition analysis of more RBD mutants including the binding and inhibition data for B.1.617 - data from two in vivo challenge models (hamster and mice)