Analyzing and modeling massive transfusion strategies and the role of fibrinogen-How much is the patient actually receiving?

BACKGROUND: Hemorrhage is a leading cause of preventable death in trauma, cardiac surgery, liver transplant, and childbirth. While emphasis on protocolization and ratio of blood product transfusion improves ability to treat hemorrhage rapidly, tools to facilitate understanding of the overall content of a specific transfusion strategy are lacking. Medical modeling can provide insights into where deficits in treatment could arise and key areas for clinical study. By using a transfusion model to gain insight into the aggregate content of massive transfusion protocols (MTPs), clinicians can optimize protocols and create opportunities for future studies of precision transfusion medicine in hemorrhage treatment. METHODS: The transfusion model describes the individual round and aggregate content provided by four rounds of MTP, illustrating that the total content of blood elements and coagulation factor changes over time, independent of the patient's condition. The configurable model calculates the aggregate hematocrit, platelet concentration, percent volume plasma, total grams and concentration of citrate, percent volume anticoagulant and additive solution, and concentration of clotting factors: fibrinogen, factor XIII, factor VIII, and von Willebrand factor, provided by the MTP strategy. RESULTS: Transfusion strategies based on a 1:1:1 or whole blood foundation provide between 13.7 and 17.2 L of blood products over four rounds. Content of strategies varies widely across all measurements based on base strategy and addition of concentrated sources of fibrinogen and other key clotting factors. DISCUSSION: Differences observed between modeled transfusion strategies provide key insights into potential opportunities to provide patients with precision transfusion strategy.

Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022.

BACKGROUND: Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN: A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS: These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION: Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION: All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.

Determination of reference ranges for the ClotPro® thromboelastometry device in paediatric patients.

BACKGROUND: A new thromboelastometry analyser (ClotPro®) was developed with advanced diagnostics. The reference ranges of ClotPro® in children ages 0-16 yr have not been reported. METHODS: In this prospective study, venous blood samples from 321 patients were obtained from children undergoing elective surgery after induction of anaesthesia. Reference ranges were defined by calculating the 2.5% and 97.5% percentiles for each age group (0-3 months, 4-12 months, 13-24 months, 2-5 yr, 6-10 yr, and 11-16 yr). RESULTS: Reference ranges of the ClotPro® analyser in all age groups demonstrated significant differences in some parameters between age groups. In the first 3 months of life, a significant shortening of the clotting time (CT) in the extrinsically activated test (EX-test) was observed in children aged 0-3 months compared with children of all older age groups (P<0.001), whereas there were no overall differences in the intrinsically activated test (IN-test). In both assays, the clot amplitude 5 and 10 min after CT (A5, A10 value) was significantly higher in the first year of life compared with children older than 1 yr (EX-test and IN-test A5 and A10, respectively; P<0.001). The strength of fibrin polymerisation (FIB-test) was significantly higher in the first 3 months of life (A5 and A10, P<0.003). CONCLUSIONS: ClotPro® reference ranges were determined for six paediatric age groups, and show age-dependent differences in specific parameters. These values will be helpful in monitoring haemostasis in paediatric patients and for developing tailored bleeding management protocols. CLINICAL TRIAL REGISTRATION: NCT04190615.

Viscoelastic Testing and Factor Concentrate Therapy to Reduce Bleeding and Transfusions in the Surgical Separation of Ischiophagus Twins: A Case Report.

The surgical procedure to separate conjoined twins represents a rare and major challenge. One of the most feared perioperative scenarios is the presence of coagulopathy secondary to bleeding. We present a case of the surgical separation of ischiopagus tetrapus twins using a patient blood management strategy encompassing a tranexamic acid infusion, intraoperative viscoelastic testing, and early fibrinogen supplementation to reduce bleeding and transfusions. This approach allowed early detection and treatment of acquired hypofibrinogenemia, which resulted in minimal exposure to blood products. This case reflects the increasing clinical interest in early avoidance of fibrinogen deficiency in complex noncardiac pediatric surgery.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of eight experts developed expert-based statements for plasma and platelet transfusions in critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement and six expert consensus statements. CONCLUSIONS: The lack of evidence precludes proposing recommendations on monitoring of the coagulation system and on plasma and platelets transfusion in critically ill pediatric patients with severe trauma, severe traumatic brain injury, or nontraumatic intracranial hemorrhage.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Noncardiac Surgery and Critically Ill Children Undergoing Invasive Procedures Outside the Operating Room: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children following noncardiac surgery and critically ill children undergoing invasive procedures outside the operating room from the Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill children undergoing invasive procedures outside of the operating room or noncardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill children following noncardiac surgery or undergoing invasive procedures outside of the operating room. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed eight expert consensus statements focused on the critically ill child following noncardiac surgery and 10 expert consensus statements on the critically ill child undergoing invasive procedures outside the operating room. CONCLUSIONS: Evidence regarding plasma and platelet transfusion in critically ill children in this area is very limited. The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding Consensus Conference developed 18 pediatric specific consensus statements regarding plasma and platelet transfusion management in these critically ill pediatric populations.

Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB).

OBJECTIVES: Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients. DESIGN: Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]). SETTING: Not applicable. PATIENTS: Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients. CONCLUSIONS: The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.

Comparison between intraoperative bleeding score and ROTEM® measurements to assess coagulopathy during major pediatric surgery.

PURPOSE: Intraoperative bleeding should be regularly assessed visually to guide coagulation management. Whereas viscoelastic testing with ROTEM® measurement has been proven to be useful in detecting coagulopathies, the visual assessment is not standardized. This study therefore aims to compare a standardized visual assessment with ROTEM® results. METHODS: A 5-point bleeding score was created and applied in a recently published randomized controlled trial in major pediatric non-cardiac surgery. This score assesses overall bleeding tendency and the occurrence of diffuse bleeding, aqueous bleeding, bleeding outside the operative field, and the ability to control bleeding. Validity of this score was tested by post hoc comparison to the results of simultaneously performed ROTEM® measurements. RESULTS: Signs of coagulopathic bleeding were assessed at 183 time points. Mild to moderate bleeding intensity was judged at 103 time points, in 42 % abnormal ROTEM® traces were obtained simultaneously. When severe bleeding was scored, abnormal ROTEM values occurred in 58 %, and FIBTEM-values were significantly lower than in the "no bleeding group". Altogether, the correlation between bleeding score and ROTEM® measurements was not significant. CONCLUSIONS: The standardized visual assessment did not correlate well with ROTEM® measurements, suggesting that it is not useful to detect coagulopathy. Trial registry number: ClinicalTrials.gov identifier No. NCT01487837.

Hemostatic Balance in Severe Trauma.

Acute coagulopathy is prevalent in adult and pediatric trauma patients and is associated with increased morbidity and mortality. While reasonable hypotheses have been created to explain the underlying perturbations of adult trauma coagulopathy (i.e., tissue factor-related increase in thrombin generation, protein C activation, hypoperfusion, and hyperfibrinolysis), only a small number of studies have been performed to prove whether these mechanisms can likewise be detected in pediatric trauma patients. In addition, severe hypofibrinogenemia (<100 mg/dL) is a frequent finding in pediatric trauma patients (>20%). Although the probability of life-threatening coagulopathy is low with minor to moderate injury, it is present in almost all patients with an injury severity score >25, hypotension, hypothermia, and acidosis. As these multifactorial changes in hemostasis cannot be adequately and rapidly measured using standard laboratory testing, the use of viscoelastic measurements has been established in adult trauma management, but prospective studies in children are urgently needed. Apart from diagnostic challenges, several studies have focused on the impact of blood product ratios on the treatment of massively bleeding pediatric trauma patients. The majority of these studies were unable to show improved survival by using higher plasma to red blood cell ratios or higher platelet to red blood cells ratios, but there are no published randomized trials to definitively answer this question. A goal-directed transfusion protocol using viscoelastic tests together with early substitution with an antifibrinolytic and fibrinogen replacement is a promising alternative to traditional ratio-based interventions. Another crucial factor in treating trauma-induced coagulopathy is the early detection of hypofibrinogenemia, a common condition in massively transfused patients. Early treatment of hypofibrinogenemia is associated with improved morbidity and mortality in adults, but needs to be further studied in future pediatric trials. Pediatric trauma patients are not only threatened by coagulopathy-related bleeding but are also at higher risk for venous thromboembolism. Pediatric trauma patients with brain injury, central venous catheters, immobilization, or surgical procedures are at highest risk for developing a deep venous thrombosis. There are no specific pediatric guidelines established to prevent venous thromboembolism in children suffering from traumatic injury.

Revisiting the Growth Modulon of Corynebacterium glutamicum Under Glucose Limited Chemostat Conditions.

Increasing the growth rate of the industrial host Corynebacterium glutamicum is a promising target to rise productivities of growth coupled product formation. As a prerequisite, detailed knowledge about the tight regulation network is necessary for identifying promising metabolic engineering goals. Here, we present comprehensive metabolic and transcriptional analysis of C. glutamicum ATCC 13032 growing under glucose limited chemostat conditions with µ = 0.2, 0.3, and 0.4 h-1. Intermediates of central metabolism mostly showed rising pool sizes with increasing growth. 13C-metabolic flux analysis (13C-MFA) underlined the fundamental role of central metabolism for the supply of precursors, redox, and energy equivalents. Global, growth-associated, concerted transcriptional patterns were not detected giving rise to the conclusion that glycolysis, pentose-phosphate pathway, and citric acid cycle are predominately metabolically controlled under glucose-limiting chemostat conditions. However, evidence is found that transcriptional regulation takes control over glycolysis once glucose-rich growth conditions are installed.

The strengths and weaknesses of viscoelastic testing compared to traditional coagulation testing.

Optimized acute bleeding management requires timely and reliable laboratory testing to detect and diagnose coagulopathies and guide transfusion therapy. Conventional coagulation tests (CCT) are inexpensive with minimal labor requirements, but CCTs may have delayed turnaround times. In addition, abnormal CCT values may not reflect in vivo coagulopathies that require treatment and may lead to overtransfusion. The use of viscoelastic testing (VET) has been rapidly expanding and is recommended by several recent bleeding guidelines. This review is intended to compare CCT to VET, review the strengths and weaknesses of both approaches, and evaluate and summarize the clinical studies that compared CCT-based and VET-based transfusion algorithms. Most studies of CCT vs VET transfusion algorithms favor the use of VET in the management of massively bleeding patients due to reductions in blood product utilization, bleeding, costs, and lengths of stay.

Viscoelastic testing in pediatric patients.

A tailored transfusion algorithm based on viscoelastic testing in the perioperative period or in trauma patients is recommended by guidelines for bleeding management. Bleeding management strategies in neonates and children are mostly extrapolated from the adult experience, as published evidence in the youngest age group is scarce. This manuscript is intended to give a structured overview of what has been published on the use of viscoelastic testing to guide bleeding management in neonates and children. Several devices that use either the traditional viscoelastic method or resonance viscoelastography technology are on the market. Reference ranges for children have been evaluated in only some of them. As most of the hemostasis maturation processes can be observed during the first year of life, adult reference ranges for viscoelastic testing could be applied over the age of 1 year. The majority of the published trials in children are based on retrospective analyses describing the correlation between viscoelastic testing and standard laboratory testing or focusing on the prediction of bleeding. Clinically more relevant studies in pediatric patients undergoing cardiac surgery have demonstrated that the implementation of a transfusion algorithm based on viscoelastic testing has significantly reduced transfusion requirements and that this approach has enabled a rapid detection of coagulation disorders in the presence of excessive bleeding. Although further studies are urgently needed, experts have reviewed the use of a transfusion algorithm based on viscoelastic testing in children as a feasible approach, as it has been shown to improve bleeding management and rationalize blood product transfusion.

Which is the preferred blood product for fibrinogen replacement in the bleeding patient with acquired hypofibrinogenemia-cryoprecipitate or fibrinogen concentrate?

The importance of the targeted treatment of acquired hypofibrinogenemia during hemorrhage with a concentrated fibrinogen product (either cryoprecipitate or fibrinogen concentrate) cannot be underestimated. Fibrinogen concentrate is a pathogen inactivated, pooled product that offers a highly purified single factor concentrate. Cryoprecipitate is a pooled product that comes with a spectrum of other coagulation factors which may further enhance (additional procoagulant effect) or even disturb (prothrombotic risk) hemostasis. The pros and cons of each product are discussed.

Essential Role of Patient Blood Management in a Pandemic: A Call for Action.

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and "flattening the curve" while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient's own blood. This multinational and diverse group of authors issue this "Call to Action" underscoring "The Essential Role of Patient Blood Management in the Management of Pandemics" and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.

Blood trauma potential of the HeartWare Ventricular Assist Device in pediatric patients.

OBJECTIVE: Mechanical circulatory support has become a standard therapy for adult patients with end-stage heart failure. For pediatric patients, technologic development lags behind with no currently approved implantable rotary blood pump. As an alternative, the HeartWare Ventricular Assist Device (Medtronic, Minneapolis, Minn), originally designed for adults, is increasingly used in pediatric patients. The aim of this multicenter study was to assess in silico, in vitro, and in vivo the blood trauma potential of this pump in pediatric application. METHODS: Clinical outcome and indicators for in vivo blood trauma were investigated retrospectively in 14 pediatric patients with the HeartWare Ventricular Assist Device (age 11.3 ± 4.8 years). Blood trauma mechanisms of the HeartWare Ventricular Assist Device were examined in silico and in vitro at an adult and pediatric operating point (5 L/min and 2.5 L/min at 2800 rpm and 2200 rpm, respectively). The flow was simulated by computational fluid dynamics and analyzed regarding flow structures, shear stresses, and washout. Hemolysis was assessed with pumps circulating bovine blood in a temperate flow circuit. RESULTS: In the retrospective in vivo analysis, lactate dehydrogenase and D-dimer values were 1.5- and 3-fold elevated, respectively, compared with adult patients with the HeartWare Ventricular Assist Device. Major bleedings were observed in 42.9%, and suspected pump thrombosis and neurologic dysfunction were observed in 14.3% of all patients. In the pediatric conditions, simulations predicted elevated mechanical stress profile below 50 Pa, more stagnant flow field, and longer washout times within the pump. In vitro measurements revealed an increased normalized index of hemolysis (17.5 vs 8.2 mg/100 L; P = .0021). CONCLUSIONS: The HeartWare Ventricular Assist Device, operated at lower speeds and flows, induces elevated blood trauma. Further studies are required to assess the clinical implications of these findings.

Improved Diagnostics Help to Identify Clinical Features and Biomarkers That Predict Mycoplasma pneumoniae Community-acquired Pneumonia in Children.

BACKGROUND: There are no reliable signs or symptoms that differentiate Mycoplasma pneumoniae (Mp) infection in community-acquired pneumonia (CAP) from other etiologies. Additionally, current diagnostic tests do not reliably distinguish between Mp infection and carriage. We previously determined that the measurement of Mp-specific immunoglobulin M antibody-secreting cells (ASCs) by enzyme-linked immunospot assay allowed for differentiation between infection and carriage. Using this new diagnostic test, we aimed to identify clinical and laboratory features associated with Mp infection. METHODS: This is a prospective cohort study of children, 3-18 years of age, with CAP from 2016 to 2017. Clinical features and biomarkers were compared between Mp-positive and -negative groups by Mann-Whitney U test or Fisher exact test, as appropriate. Area under the receiver operating characteristic curve (AUC) differences and optimal thresholds were determined by using the DeLong test and Youden J statistic, respectively. RESULTS: Of 63 CAP patients, 29 were Mp-positive (46%). Mp positivity was statistically associated with older age (median, 8.6 vs 4.7 years), no underlying disease, family with respiratory symptoms, prior antibiotic treatment, prolonged prodromal respiratory symptoms and fever, and extrapulmonary (skin) manifestations. Lower levels of C-reactive protein, white blood cell count, absolute neutrophil count, and procalcitonin (PCT), specifically PCT <0.25 µg/L, were statistically associated with Mp infection. A combination of age >5 years (AUC = 0.77), prodromal fever and respiratory symptoms >6 days (AUC = 0.79), and PCT <0.25 µg/L (AUC = 0.81) improved diagnostic performance (AUC = 0.90) (P = .05). CONCLUSIONS: A combination of clinical features and biomarkers may aid physicians in identifying patients at high risk for Mp CAP.

Fibrinogen Supplementation and Its Indications.

Adequate plasma levels of fibrinogen are essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than other coagulation factors. Although the critical minimum concentration of fibrinogen to maintain hemostasis is a matter of debate, many patients with coagulopathic bleeding require fibrinogen supplementation. Among the treatment options for fibrinogen supplementation, fibrinogen concentrate may be viewed by some as preferable to fresh frozen plasma or cryoprecipitate. The authors review major studies that have assessed fibrinogen treatment in trauma, cardiac surgery, end-stage liver disease, postpartum hemorrhage, and pediatric patients. Some but not all randomized controlled trials have shown that fibrinogen concentrate can be beneficial in these settings. The use of fibrinogen as part of coagulation factor concentrate based therapy guided by point-of-care viscoelastic coagulation monitoring (ROTEM [rotational thromboelastometry] or TEG [thromboelastography]) appears promising. In addition to reducing patients' exposure to allogeneic blood products, this strategy may reduce the risk of complications such as transfusion-associated circulatory overload, transfusion-related acute lung injury, and thromboembolic adverse events. Randomized controlled trials are challenging to perform in patients with critical bleeding, and more evidence is needed in this setting. However, current scientific rationale and clinical data support fibrinogen repletion in patients with ongoing bleeding and confirmed fibrinogen deficiency.