Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia-a prospective, single-center, analytical, cross-sectional study.

Background: Patients with hematological malignancies (HM) frequently present thrombocytopenia and higher risk of bleeding. Although transfusion is associated with higher risk of adverse events and poor outcomes, prophylactic transfusion of platelets is a common practice to prevent hemorrhagic complications. Thromboelastometry has been considered a better predictor for bleeding than isolated platelet counts in different settings. In early stages of sepsis, hypercoagulability may occur due to higher fibrinogen levels. Objectives: To evaluate the behavior of coagulation in patients with HM who develop sepsis and to verify whether a higher concentration of fibrinogen is associated with a proportional increase in maximum clot firmness (MCF) even in the presence of severe thrombocytopenia. Methods: We performed a unicentric analytical cross-sectional study with 60 adult patients with HM and severe thrombocytopenia, of whom 30 had sepsis (sepsis group) and 30 had no infections (control group). Coagulation conventional tests and specific coagulation tests, including thromboelastometry, were performed. The main outcome evaluated was MCF. Results: Higher levels of fibrinogen and MCF were found in sepsis group. Both fibrinogen and platelets contributed to MCF. The relative contribution of fibrin was significantly higher (60.5 ± 12.8% vs 43.6 ± 9.7%; P < .001) and that of platelets was significantly lower (39.5 ± 12.8% vs 56.4 ± 9.7%; P < .001) in the sepsis group compared with the control group. Conclusion: Patients with sepsis and HM presented higher concentrations of fibrinogen than uninfected patients, resulting in greater MCF amplitudes even in the presence of thrombocytopenia.

Management and outcomes of pregnant ICU patients with severe COVID-19 pneumonia in Qatar: A retrospective cohort study.

INTRODUCTION: Pregnant women are considered a high-risk group for COVID-19 due to their increased vulnerability to viral infections. The impact of COVID-19 on pregnant women is not well understood, and there is a need for data on managing severe COVID-19 in pregnant patients. This retrospective descriptive cohort study described the characteristics, hospital stay, interventions, and outcomes of pregnant patients admitted to the intensive care units (ICUs) with severe COVID-19 pneumonia in Qatar. METHODS: Data were collected from medical records and chart reviews of pregnant women admitted to Hamad Medical Corporation (HMC) with COVID-19 pneumonia from March 01, 2020, to July 31, 2021. The inclusion criteria encompassed pregnant women with a positive polymerase chain reaction (PCR) antigen test or radiological changes at admission, requiring respiratory support, and hospitalized for more than 24 hours. RESULTS: A total of 43 pregnant women were included in this study. Most patients were admitted during the first wave of the pandemic, with a median gestational age of 212 days [interquartile range 178-242 days] at presentation. The most common respiratory support methods were high-flow nasal cannula, non-invasive positive pressure ventilation, and invasive positive pressure ventilation. Convalescent plasma therapy was administered to 58% of patients, and tocilizumab was used in 28%. Renal replacement therapy was required by 4.6% of patients and 7% required extracorporeal membrane oxygenation. CONCLUSION: This study provides valuable insights into the impact of COVID-19 on pregnant patients admitted to the ICUs in Qatar. The results suggest that pregnant patients with COVID-19 pneumonia require close monitoring and appropriate interventions to minimize adverse outcomes for both mother and fetus. The data may contribute to future guidelines and management strategies for severe COVID-19 in pregnant patients.

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.

Nurse-run preanaesthesia assessment clinics: an initiative towards improving the quality of perioperative care at the ambulatory care centre.

INTRODUCTION: Nurse-run preanaesthesia assessment is well established in ambulatory surgery. However, in the Middle East the implementation of such a service is new and needed careful preparation. Aim of this audit is to assess the feasibility and the quality of preoperative assessments by the specially trained nurses, patient and nurse satisfaction and overall perioperative quality of recovery. METHODS: The nurses were selected and trained first in an accredited programme. Then an implementation period of 3 month was used for them to gain experience. Hereafter, we performed a four-step audit on the quality of preassessment, the patient's satisfaction, the quality of recovery and adverse events if any. Finally, we also monitored the nurse's satisfaction of their new advanced role. RESULTS: The quality of preanaesthesia assessment was high as with 95% compliance to the accepted standards. In the patient satisfaction survey, all 152 patients were either highly satisfied or satisfied with the nurse-run service. The nurses were also highly satisfied and felt that they were either highly or moderately valued. All the patients who were operated at the ambulatory care services were followed up postoperatively by telephone calls which revealed that most of them were highly satisfied. No major or minor adverse events occurred. CONCLUSION: Our specially trained nurses perform preoperative assessments on high standard without adverse events, while patient and staff satisfaction is very high. Future projects will focus on reducing the rate of cancellation of surgeries, investigating the cost-effectiveness of this approach as well as training the specialised nurses for paediatric preoperative anaesthesia assessments. This model of care could induce further nurse-run models of care in the Middle East.

Point-of-Care Platelet Function Monitoring: Implications for Patients With Platelet Inhibitors in Cardiac Surgery.

Although most physicians are comfortable managing the limited anticoagulant effect of aspirin, the recent administration of potent P2Y12 receptor inhibitors in patients undergoing cardiac surgery remains a dilemma. Guidelines recommend discontinuation of potent P2Y12 inhibitors 5- to- 7 days before surgery to reduce the risk of postoperative hemorrhage. Such a strategy might not be feasible before urgent surgery, due to ongoing myocardial ischemia or in patients at high risk for thromboembolic events. Recently, different point-of-care devices to assess functional platelet quality have become available for clinical use. The aim of this narrative review was to evaluate the implications and potential benefits of platelet function monitoring in guiding perioperative management and therapeutic options in patients treated with antiplatelets, including aspirin or P2Y12 receptor inhibitors, undergoing cardiac surgery. No objective superiority of one point-of-care device over another was found in a large meta-analysis. Their accuracy and reliability are generally limited in the perioperative period. In particular, preoperative platelet function testing has been used to assess platelet contribution to bleeding after cardiac surgery. However, predictive values for postoperative hemorrhage and transfusion requirements are low, and there is a significant variability between and within these tests. Further, platelet function monitoring has been used to optimize the preoperative waiting period after cessation of dual antiplatelet therapy before urgent cardiac surgery. Furthermore, studies assessing their value in therapeutic decisions in bleeding patients after cardiac surgery are scarce. A general and liberal use of perioperative platelet function testing is not yet recommended.

Flow controlled ventilation in Acute Respiratory Distress Syndrome associated with COVID-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: This study aims to demonstrate the positive effects on oxygenation of flow-controlled ventilation compared to conventionally ventilated patients in patients suffering from Acute respiratory distress syndrome (ARDS) associated with COVID-19.We define ARDS according to the "Berlin" definition integrating the oxygenation index (P/F ratio), the level of Positive End Expiratory Pressure (PEEP), radiological and clinical findings. TRIAL DESIGN: This is a prospective, randomized (1:1 ratio), parallel group feasibility study in adult patients with proven COVID-19 associated ARDS. PARTICIPANTS: All adult patients admitted to the ICU of Hamad Medical Corporation facilities in Qatar because of COVID-19 infection who develop moderate to severe ARDS are eligible. The inclusion criteria are above 18 years of age, proven COVID-19 infection, respiratory failure necessitating intubation and mechanical ventilation, ARDS with a P/F ratio of at least 200mmHg or less and a minimum PEEP 5cmH2O, BMI less 30 kg/ m2. The following exclusion criteria: no written consent, chronic respiratory disease, acute or chronic cardiovascular disease, pregnancy or need for special therapy (prone position and/or Extracorporeal membrane oxygenation). INTERVENTION AND COMPARATOR: After randomisation, the group A patients will be ventilated with the test-device for 48 hours. The settings will be started with the pre-existing-PEEP. The upper pressure will be determined to achieve a tidal volume of 6 ml/kg lean body mass, while the respiratory rate will be set to maintain an arterial pH above 7.2. In group B, the ventilator settings will be adjusted by the attending ICU team in accordance with lung-protective ventilation strategy. All other treatment will be unchanged and according to our local policies/guidelines. MAIN OUTCOMES: The primary end point is PaO2. As this is a dynamic parameter, we will record it every 6-8 hours and analyse it sequentially. RANDOMISATION: The study team screens the ventilated patients who fulfil the inclusion criteria and randomise using a 1:1 allocation ratio after consenting using a closed envelope method. The latter were prepared and sealed in advance by an independent person. BLINDING (MASKING): Due to the technical nature of the study (use of a specific ventilator) blinding is only possible for the data-analysts and the patients. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation based on the assumption of an effect size (change in PaO2) of 1.5 SDS in the primary endpoint (PaO2), an intended power of 80%, an alpha error of 5% and an equal sample ratio results in n=7 patients needed to treat. However, to compensate for dropouts we will include 10 patients in each group, which means in total 20 patients. TRIAL STATUS: The local registration number is MRC-05-018 with the protocol version number 3. The date of approval is 14th April 2020. Recruitment began 28th May 2020 and is expected to end in September 2020. TRIAL REGISTRATION: The protocol was registered before starting subject recruitment under the title: "Flow controlled ventilation in ARDS associated with COVID-19" in ClinicalTrials.org with the registration number: NCT04399317 . Registered on 22 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Anticoagulation in critically ill patients on mechanical ventilation suffering from COVID-19 disease, The ANTI-CO trial: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. TRIAL DESIGN: This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. EXCLUSION CRITERIA: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. INTERVENTION AND COMPARATOR: The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. RANDOMISATION: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. BLINDING (MASKING): Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). TRIAL STATUS: The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. TRIAL REGISTRATION: The protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial" in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Is Migraine an MPV-Related Disease? An Observational Study of Polish Neurological Patients.

Many studies have found correlations between abnormal MPV and clinical reactivity in a variety of diseases. In the present paper, we sought MPV-related neurological diseases that are less frequently reported in the literature. The electronic medical records of 852 neurological patients with mean platelet volume (MPV) measurements (F = 45%, age = 55.7 ± 18.7, 8-104) were searched after the patients had received a diagnosis of a neurological disease (new and old episodes) according to the nine classes of the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10). A set of consecutive statistical methods (i.e., cluster analysis, segmented regression, linear correlation, propensity score matching, and mixed effects Poisson regression) were used to establish a link between MPV and neurological disease. A statistically significant (p < 0.05) relationship with MPV was found only in pain syndrome patients, with seven out of eight clinically diagnosed migraine episodes. With all other ICD-10 classes of neurological diseases, the effect of MPV was found to be nonsignificant (p > 0.05). MPV may implicate a clinical relationship with pain syndrome and migraine episodes. More complex statistics could help analyse data and find new correlations.

Shifts of Transfusion Demand in Cardiac Surgery After Implementation of Rotational Thromboelastometry-Guided Transfusion Protocols: Analysis of the HEROES-CS (HEmostasis Registry of patiEntS in Cardiac Surgery) Observational, Prospective Open Cohort Database.

OBJECTIVES: Rotational thromboelastometry (ROTEM)-guided transfusion algorithms in cardiac surgery have been proven to be successful in reducing blood loss in randomized controlled trials. Using an institutional hemostasis registry of patients in cardiac surgery (HEROES-CS), the authors hypothesized that the use of ROTEM-guided transfusion algorithms would save blood products and overall costs in cardiac surgery in every day practice. DESIGN: Observational, prospective open cohort database. SETTING: Single-center academic hospital. PARTICIPANTS: Cardiac surgery patients. INTERVENTIONS: Implementation of ROTEM-guided bleeding management. MEASUREMENTS AND MAIN RESULTS: A classical-guided algorithm and a ROTEM-guided algorithm were used for patient blood management in 2 cohorts. Primary outcome was the use and amount of blood products and hemostatic medication. Secondary outcomes were amount of rethoracotomies, length of stay, and 30-day mortality. Finally, costs and savings were calculated. The classical-guided cohort comprised 204 patients, and ROTEM-guided cohort comprised 151 patients. Baseline characteristics showed excellent similarities after propensity score matching of 202 patients. Blood loss was lower after ROTEM guidance (p < 0.001). Absolute risk reduction was 17% for red blood cells (p = 0.024), 12% for fresh frozen plasma (p = 0.019), and 4% for thrombocyte concentrates (p = 0.582). More tranexamic acid was given, but not more fibrinogen concentrate, while desmopressin was given less often. Hospital length of stay was reduced by an overall median of 2 and a mean of 4 days (p < 0.001). Mortality and rethoracotomy rates were not affected. Potential savings were about €4,800 ($5,630) per patient. CONCLUSIONS: Implementation of a ROTEM-guided transfusion algorithm in cardiac surgery patients reduced the use of blood products and hemostatic medication, hereby saving costs. Reductions in mortality and rethoracotomy rates could not be found.

Surgical intensive care - current and future challenges?

Bjorn Ibsen, an anesthetist who pioneered positive pressure ventilation as a treatment option during the Copenhagen polio epidemic of 1952, set up the first Intensive Care Unit (ICU) in Europe in 1953. He managed polio patients on positive pressure ventilation together with physicians and physiologists in a dedicated ward, where one nurse was assigned to each patient. In that sense Ibsen is more or less the father of intensive care medicine as a specialty and also an advocate of the one-to-one nursing ratio for critically ill patients. Nowadays, the Surgical Intensive Care Unit (SICU) offers critical care treatment to unstable, severely, or potentially severely ill patients in the perioperative setting, who have life-threatening conditions and require comprehensive care, constant monitoring, and possible emergency interventions. Hence there is one very specific challenge in the surgical setting: the intensivist has to manage the patient flow starting from admission to the hospital through to the operating theater, in the SICU, and postoperatively for the discharge to the ward. In other words, the planning of the resources (most frequently availability of beds) has to be optimized to prevent cancellations of elective surgical procedures but also to facilitate other emergency admissions. SICU intensivists take the role of arbitrators between surgical demand and patient's interests. This means they supervise the safety, efficacy, and workability of the process with respect to all stakeholders. This notion was reported in 2007 when Stawicki and co-workers performed a small prospective study concluding that it appears safe if the dedicated intensivist takes over the role of the last arbitrator supported by a multidisciplinary team.1 However, demographic changes in many countries during the last few decades have given rise to populations which are more elderly and sicker than before. This impacts on the healthcare system in general but on the intensivist and the ICU team too. In addition, in a society with an increased life expectancy, the balance between treatable disease, outcome, and utilization of resources must be maintained. This fact gains even more importance as patients and their families claim "high end" treatment. Such a demand is reflected looking at the developments that have taken place over the last 25 years. Mainly, the focus of intensive care medicine was on technical support or even replacement of failing organ systems such as the lungs, the heart, or the kidneys by veno-venous extracorporeal membrane oxygenation (VV-ECMO), veno-arterial ECMO (VA-ECMO), and continuous veno-venous hemofiltration (CVVH) respectively. This means "technical care" became a core capability and expectation of critical care medicine. In parallel, medical treatment became more standardized. For example, lung protective ventilation strategies, early enteral feeding, and daily sedation vacation are part of modern protocols. As a consequence, ventilator time has been reduced and patients therefore develop delirium less frequently. These measures, beside others, are implemented in care bundles to improve the quality of care of patients by the whole ICU team. The importance of specialty trained teams was already pointed out 35 years ago when Li et al.,2 demonstrated in a study performed in a community hospital that the mortality was decreased if an ICU was managed 24/7 by an on-site physician. The association of improved outcomes and presence of a critical care trained physician (intensivist) has been shown in several studies since that time.3,4,5,6 A modern multidisciplinary critical care team consists at least of an intensivist, ICU nurse, pharmacist, respiratory therapist, physiotherapist, and the primary team physician. Based on clinical needs, the team can be supplemented by oncologists, cardiologists, or other specialties. Again, this approach is supported by research: a recent retrospective cohort study from the California Hospital Assessment and Reporting Taskforce (CHART) on 60,330 patients confirmed the association between improved patient outcome and such a multidisciplinary team.7 If such an intensive care team makes a difference, why do not all patients at risk receive advanced ICU-care? It was already demonstrated by Esteban et al., in a prospective study that patients with severe sepsis had a mortality rate of 26% when not admitted to an ICU in comparison to 11% when they were admitted to an ICU.8 Meanwhile, we know that early referral is particularly important, because for ischemic diseases the timing appears to make a difference in terms of full recovery. So, the following questions arise: Should intensive care be rolled out to each ward and physical admission to an ICU or be restricted to special cases only? For this purpose, the so-called "Rapid Response Teams" (RRT) or "Medical Emergency Team" (MET), which essentially are a form of an ICU outreach team, were implemented. The name, composition, or exact role of such team varies from institution to institution and country to country. Alternatively, should all ward staff be educated to recognize sick patients earlier for a timely transfer to a dedicated area? This would mean that ICU-care would be introduced in the ward. A first attempt to answer this question, whether to deploy critical care resources to deteriorating patients outside the ICU 24/7, was given by Churpek et al.9 The success of the rapid response teams could be related to decreased rates of cardiac arrest outside the ICU setting and in-hospital mortality. Interestingly, an analysis of the registry database of the RRT calls in this study showed that the lowest frequency of calls occurred between 1:00 AM to 6:59 AM time period. In contrast, the mortality was highest around 7 AM and lowest during noon hour. This indicates that not simply the availability of such a team makes a difference but also the alertness of the ward-teams is of high importance to identify deteriorating patients in a timely manner. Essentially, this would necessitate ward staff being trained to provide a higher level of care enabling them to better recognize when patients become sicker to avoid a delayed call to the ICU. Alternatively, a system in which the intensivist plays a major role in daily ward rounds could be beneficial. So, the ward doctor should become an intensivist. However, the latter means the ICU is rolled out across the whole hospital which would consume a huge amount of resources. Another option would be 24/7 remote monitoring of patients at risk that notifies the intensivist or RRT in case of need. The infrastructure, technology, and manpower to put this in place also has associated costs. As the demand for ICU care will rise further in the future, intensivists will play an even more important role in the healthcare system that itself is under enormous economic pressure to ensure the best quality of care for critically ill patients. Besides excellent knowledge and hard skills, intensivists need to be team players, communicators, facilitators, and arbitrators to achieve the best results in collaboration with all involved in patient treatment.

Preoperative screening for bleeding disorders: A comprehensive laboratory assessment of clinical practice.

BACKGROUND: Patients with mild bleeding disorders are at risk of perioperative bleeding, but screening for these disorders remains challenging. OBJECTIVES: We aimed to assess the prevalence of hemostatic abnormalities in patients with and without reported bleeding symptoms on a preoperative questionnaire, consisting of guideline-proposed questions, and appraised the diagnostic value of several screening modalities for the identification of patients with hemostatic abnormalities. METHODS: In this observational study, 240 patients with and 95 patients without bleeding symptoms on the preoperative questionnaire were included. Patients with known bleeding disorders, antithrombotic drugs, thrombocytopenia, and anemia were excluded. Preoperatively, all patients underwent elaborate hemostatic testing. Hemostatic abnormalities were defined as coagulation, vWF, or fibrinolysis factor levels below reference range and platelet function defects. Screening modalities included the ISTH Bleeding Assessment Tool (ISTH-BAT), PT, aPTT, TT, Euglobulin Lysis Time (ELT), and Platelet Function Analyser (PFA). RESULTS: In 21 of 240 (8.8%) patients reporting bleeding symptoms, hemostatic abnormalities were found, including 7 reduced coagulation factor levels, 10 platelet function abnormalities, and 4 reduced vWF levels. In comparison, 10 of 95 (10.5%) patients not reporting bleeding symptoms had abnormalities. The ISTH-BAT could not identify patients with abnormalities, while PT, aPTT, TT, ELT, and PFA had high specificity but low sensitivity to detect abnormalities. CONCLUSIONS: The prevalence of hemostatic abnormalities in both patients with and without reported bleeding symptoms was 9%-10%. This suggests that the guideline-based questionnaire cannot differentiate between patients with and without abnormalities, while the discriminative power of the screening modalities is also limited.

Thromboelastometric prediction of mortality using the kinetics of clot growth in critically ill septic patients.

: Sepsis induces alterations in blood coagulation which are associated with mortality. Using rotational thromboelastometry (ROTEM), these states are often characterized by changes in parameters representing terminal clot lysis. However, the ROTEM changes are often subtle, making them difficult to recognize and interpret. The objective of this study is to evaluate a new ROTEM clot velocity parameter representing clot formation kinetics in septic ICU patients. We hypothesized that this time-based parameter was significantly different in critically ill septic survivors vs. nonsurvivors. This retrospective observational study included severe sepsis and septic shock patients having a minimum of two organ dysfunctions by Sequential Organ Failure Assessment criteria (study group), and a control group of healthy adults without infection . ROTEM with EXTEM activation was performed in all groups. The time from maximal clot formation velocity to zero velocity, representing the latter portion of time during active clot formation prior to achieving maximal clot firmness (t-AUCi) was calculated along with other ROTEM parameters and compared between septic survivors, nonsurvivors and healthy controls. A total of 76 septic patients, of which 26.3%, survived, were included in the study group, and 26 healthy control individuals were included in the control group. t-AUCi correlated with terminal clot lysis (P < 0.001), and was significantly prolonged in septic nonsurvivors compared with survivors and healthy controls (P < 0.001). t-AUCi also differentiated nonsurvivors vs. survivors among those patients having similar ROTEM lysis indices. t-AUCi was useful to differentiate critically ill septic patients, and could be useful to identify septic patients with high-risk of ICU mortality.

Hypobaric Hypoxia Causes Elevated Thrombin Generation Mediated by FVIII that is Balanced by Decreased Platelet Activation.

INTRODUCTION: Epidemiological studies suggest that hypobaric hypoxia at high altitude poses a risk for developing venous thromboembolism. The cause of this observed hypercoagulability remains unclear. Therefore, this study aimed to investigate the effect of hypobaric hypoxia at 3,883 m above sea level on thrombin generation and platelet activation. METHODS: After complying with medical ethical procedures, 18 participants were recruited, of whom 1 had to leave the study prematurely due to mild acute mountain sickness. Blood was drawn first at 50 m above sea level and second at 3,883 m altitude after gradual acclimatization for 6 days. Thrombin generation was measured in whole blood, platelet-rich plasma and platelet-poor plasma. Platelet activation was assessed using a whole blood flow-cytometric assay. Coagulation factor levels, D-dimer levels and markers of dehydration and inflammation were measured. RESULTS: Hypobaric hypoxia at 3,883 m altitude caused increased thrombin generation, measured as peak height and endogenous thrombin potential, in whole blood, platelet-rich and platelet-poor plasma without or at low tissue factor concentration. The elevated thrombin generation was mediated by increased factor VIII levels and not caused by dehydration or inflammation. In contrast, spontaneous and agonist-induced platelet activation was decreased at high altitude. CONCLUSION: Hypobaric hypoxia causes increased factor VIII-mediated thrombin generation. The hypercoagulability was balanced by decreased platelet activation. These findings may explain why venous, and not arterial thrombotic events occur more frequently at high altitude.

Thromboelastometry profile in critically ill patients: A single-center, retrospective, observational study.

BACKGROUND: Transfusion therapy is associated with increased morbidity, mortality and costs. Conventional coagulation tests (CCT) are weak bleeding predictors, poorly reflecting coagulation in vivo. Thromboelastometry (ROTEM) provides early identification of coagulation disorders and can guide transfusion therapy by goals, reducing blood components transfusion. OBJECTIVE: The aim of this study is to describe coagulation profile of critically ill patients using ROTEM and evaluate the association between CCT and thromboelastometry. METHODS: This is a retrospective, observational study conducted in medical-surgical intensive care unit (ICU). Adult patients (≥18 years) admitted to ICU between November 2012 and December 2014, in whom ROTEM analyses were performed for bleeding management were included in this study. The first ROTEM and CCT after ICU admission were recorded simultaneously. Additionally, we collected data on blood components transfusion and hemostatic agents immediately after laboratory tests results. RESULTS: The study included 531 patients. Most ROTEM tests showed normal coagulation profile [INTEM (54.8%), EXTEM (54.1%) and FIBTEM (53.3%)] with divergent results in relation to CCT: low platelet count (51.8% in INTEM and 55.9% in EXTEM); prolonged aPTT (69.9% in INTEM and 63.7% in EXTEM) and higher INR (23.8% in INTEM and 27.4% in EXTEM). However 16,7% of patients with normocoagulability in ROTEM received platelet concentrates and 10% fresh frozen plasma. CONCLUSION: The predominant ROTEM profile observed in this sample of critically ill patients was normal. In contrast, CCT suggested coagulopathy leading to a possibly unnecessary allogenic blood component transfusion. ROTEM test may avoid inappropriate allogeneic blood products transfusion in these patients.

Effects of malignancy on blood coagulation in septic intensive care patients.

: The objectives of the study are to examine the effect of sepsis on the coagulation profile of patients having solid cancer and to test the hypothesis that septic patients with cancer have normal or increased hemostatic capacity despite prolonged standard coagulation tests (SCTs) compared with noninfected cancer patients. Patients with solid cancer were included in the study forming two groups: study group included patients with sepsis with minimum two organ dysfunctions and control group formed by noninfected cancer patients. SCTs, platelet count, plasma levels of coagulation factors and rotation thromboelastometry (TEM International GmbH, Munich, Germany) were determined in both groups. Study group patients (n = 35) showed prolonged SCTs, thrombocytopenia, decreased coagulation factor levels and increased D-dimer compared with control group (n = 35). However, fibrinogen levels and clot firmness assessed by rotation thromboelastometry were not different between groups and clot lysis indexes at 45 and 60 min were increased in study group compared with control group. The first derivative of the clot firmness curve revealed an increased time to the maximum velocity of clot formation for study group, without differences in the maximum velocity of clot formation, or in total thrombus formation. Sepsis with organ dysfunction in cancer patients is associated with delayed initiation of coagulation and reduced fibrinolysis compared with control patients, but overall clot formation and stabilization is not different. For septic cancer patients, SCTs and plasmatic indicators of fibrinolysis do not translate well to whole blood clot formation and may be misleading indicators of thrombotic or bleeding risk.

Practical guidance on the use of laboratory testing in the management of bleeding in patients receiving direct oral anticoagulants.

Direct oral anticoagulants (DOACs) have demonstrated a favorable benefit-risk profile in several thromboembolic disorders and are increasingly used in routine clinical practice. A number of real-world studies on DOACs are ongoing, and data published so far have shown broadly similar outcomes to those demonstrated in the respective phase III trials. Despite their beneficial attributes, bleeding risk (as with any other anticoagulants) is often a concern for physicians when prescribing DOACs, particularly in elderly patients, those with significant comorbidities, and other high-risk patient populations. Although the absence of routine coagulation monitoring is an advantage of the DOACs, measuring their anticoagulant effect and/or plasma drug levels may be helpful in certain clinical scenarios to help patient management and improve outcomes. In this paper, practical guidance and recommendations are provided for clinical situations in which the test results may aid clinical decision-making, including patients with life-threatening bleeding events, patients without bleeding but with test results indicating a risk of bleeding, for those patients with a suspected thromboembolism while receiving a DOAC, or prior to patients undergoing elective or urgent surgical procedures. Finally, appropriate monitoring of the DOACs could be of substantial benefit to patients, and there is a high potential for development in this area in the future.

Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016.

: The management of perioperative bleeding involves multiple assessments and strategies to ensure appropriate patient care. Initially, it is important to identify those patients with an increased risk of perioperative bleeding. Next, strategies should be employed to correct preoperative anaemia and to stabilise macrocirculation and microcirculation to optimise the patient's tolerance to bleeding. Finally, targeted interventions should be used to reduce intraoperative and postoperative bleeding, and so prevent subsequent morbidity and mortality. The objective of these updated guidelines is to provide healthcare professionals with an overview of the most recent evidence to help ensure improved clinical management of patients. For this update, electronic databases were searched without language restrictions from 2011 or 2012 (depending on the search) until 2015. These searches produced 18 334 articles. All articles were assessed and the existing 2013 guidelines were revised to take account of new evidence. This update includes revisions to existing recommendations with respect to the wording, or changes in the grade of recommendation, and also the addition of new recommendations. The final draft guideline was posted on the European Society of Anaesthesiology website for four weeks for review. All comments were collated and the guidelines were amended as appropriate. This publication reflects the output of this work.

The use of regression analysis in determining reference intervals for low hematocrit and thrombocyte count in multiple electrode aggregometry and platelet function analyzer 100 testing of platelet function.

Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r2 ≥ 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r2 = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

Near-Patient Thrombin Generation in Patients Undergoing Elective Cardiac Surgery.

BACKGROUND: Measuring thrombin generation (TG) in plasma increasingly gained attention as a diagnostic tool in the field of thrombosis and hemostasis. To include the contribution of all blood cells, recently, the whole blood TG method was developed. METHODS: We changed the calculation method of the standard calibrated automated thrombography (CAT) to a method only taking into account the data until the peak of TG, thereby considerably reducing the time from blood draw to result. By redesigning the method, the blood volume per test was reduced to 15 µL. RESULTS: For all TG parameters, the interassay variation proved to be below 15%. The interindividual variation of all parameters was comparable to the CAT method. Thirty-three patients undergoing cardiothoracic surgery were included to investigate whether our assay correlates with postoperative blood loss. On dividing patients into severe and mild bleeders, significant differences between both groups were found for the peak endogenous thrombin potential (peakETP) and peak values determined by our near-patient device. Importantly, patients with a peakETP below the median experienced significantly more blood loss compared to those with a peakETP above the median. A similar division based on the peak as well as the body mass index of the patient yielded similar significant differences. A combination of the peakETP, the body mass index, and the lag time even resulted in a better predictor of blood loss compared to each parameter separately. CONCLUSIONS: Our adapted whole blood TG assay can be used near patients and is indicative for the amount of blood loss post cardiothoracic surgery.