[Coagulation disorders in liver cirrhosis - Diagnostics and management]. / Gerinnungsstörungen bei Leberzirrhose ­ Diagnostik und Management.

Patients with liver cirrhosis often exhibit complex alterations in their hemostatic system that can be associated with both bleeding and thrombotic complications. While prophylactic correction of abnormal coagulation parameters should be avoided, an individualized approach is recommended prior to invasive procedures, whereby specific preventive measures to stabilize hemostasis should be based on the periprocedural bleeding risk. While the haemostatic system of patients with compensated cirrhosis is often in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic factors, a decompensation of liver cirrhosis can lead to destabilization of this fragile equilibrium. Since conventional coagulation tests do not adequately capture the complex changes in the hemostatic system in cirrhosis, functional analysis methods such as viscoelastic tests or thrombin generation assays can be used for evaluating the coagulation status. This review describes the underlying pathophysiological changes in the hemostatic system in liver cirrhosis, provides an overview of diagnostic methods and discusses therapeutic measures in case of bleeding and thrombotic complications.

Patient Blood Management Program Implementation: Comprehensive Recommendations and Practical Strategies.

INTRODUCTION: Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems. METHODS: In this context, acknowledging that blood transfusions are essentially heterologous cell transplantations, the use of therapeutic options has gained strength and is collectively known as the patient blood management (PBM) program. PBM is an approach based on three main pillars: (1) treating anemias and coagulopathies in an optimized manner, especially in the preoperative period; (2) optimizing perioperative hemostasis and the use of blood recovery systems to avoid the loss of the patient's blood; (3) anemia tolerance, with improved oxygen delivery and reduced oxygen demand, particularly in the postoperative period. RESULTS: Current scientific evidence supports the effectiveness of PBM by reducing the need for blood transfusions, decreasing associated complications, and promoting more efficient and safer blood management. Thus, PBM not only improves clinical outcomes for patients but also contributes to the economic sustainability of healthcare systems. CONCLUSION: The aim of this review was to summarize PBM strategies in a comprehensive, evidence-based approach through a systematic and structured model for PBM implementation in tertiary hospitals. The recommendations proposed herein are from researchers and experts of a high-complexity university hospital in the network of the Sistema Único de Saúde, presenting itself as a strategy that can be followed as a guideline for PBM implementation in other settings.

Hematologic Emergencies: Recognition and Initial Management.

Hematologic emergencies are bleeding or clotting disorders that are hereditary or acquired and must be treated emergently to avoid significant morbidity or mortality. Patients experiencing a hematologic emergency may present with spontaneous bleeding, jaundice, petechiae, or purpura. Initial diagnostic testing should include a complete blood count. Patients who have bleeding associated with a hereditary disorder should receive clotting factor replacement before diagnostic testing. Acute chest syndrome is an uncommon but serious complication of sickle cell disease. Hemolysis caused by autoimmune disorders or iatrogenic errors from blood product transfusions has a distinct clinical presentation and requires immediate action. Severe thrombocytopenia presenting as immune or thrombotic thrombocytopenic purpura should be differentiated and treated appropriately. Disseminated intravascular coagulation and trauma coagulopathy are sometimes confused with each other, but both can cause serious injury and require unique treatments. Primary care physicians should promptly recognize patients who require emergent referral to a hematologic specialist.

Factor Eight Inhibitor Bypassing Activity as First-line Therapy for Coagulopathy in Cardiac Surgery.

OBJECTIVES: To compare the outcomes of factor eight inhibitor bypassing activity (FEIBA) versus fresh frozen plasma (FFP) as the primary treatment for postoperative coagulopathy in patients undergoing cardiac surgery. DESIGN: A retrospective, propensity-matched study. SETTING: A single, tertiary hospital. PARTICIPANTS: Patients who underwent noncoronary cardiac surgery with cardiopulmonary bypass between 2015 and 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We stratified patients into 2 groups based on whether they received intraoperative FFP or FEIBA; cases using both were excluded. We analyzed 434 cases, with 197 receiving FFP and 237 receiving FEIBA. After propensity matching, there was no significant difference in the proportion of the patients who required packed red blood cell transfusions (p = 0.08). However, of those who required packed red blood cell transfusions, patients in the FEIBA group required significantly fewer units of packed red blood cells (p < 0.001). Significantly fewer patients in the FEIBA group required platelet (p < 0.001) and cryoprecipitate (p < 0.001) transfusions. The FEIBA group showed decreased prolonged postoperative intubation (p = 0.05), decreased intensive care unit length of stay (p = 0.04), and lower 30-day readmission rates (p = 0.03). There were no differences in the rates of thrombotic complications between the 2 cohorts. CONCLUSIONS: In the initial treatment of postcardiopulmonary bypass coagulopathy, FEIBA may be more effective than FFP in decreasing blood product transfusions and readmission rates. Further studies are needed to explore the potential routine use of FEIBA as first-line agent in this patient population.

INVESTIGATING THE RELATIONSHIP BETWEEN BLEEDING, CLOTTING, AND COAGULOPATHY DURING AUTOMATED PARTIAL REBOA STRATEGIES IN A HIGHLY LETHAL PORCINE HEMORRHAGE MODEL.

ABSTRACT: Background: Death due to hemorrhagic shock, particularly, noncompressible truncal hemorrhage, remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently, whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer. In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared with pREBOA due to more oscillatory flow. Methods: Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 min of automated pREBOA, iREBOA, or no balloon support (control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., eight key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 min). Citrated kaolin heparinase assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. Results: As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between the iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R time: P < 0.001; K time: P < 0.001) and clot strength (MA: P = 0.01; G: P = 0.02) over the duration of the experiment. Conclusions: Despite observing acute differences in peak proximal pressures between the iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA.

Coagulation abnormalities associated with CAR-T-cell therapy in haematological malignancies: A review.

Chimeric antigen receptor (CAR)-T-cell therapy has demonstrated considerable efficacy and safety in the treatment of patients with relapsed/refractory haematological malignancies. Owing to significant advances, CAR-T-cell therapeutic modality has undergone substantial shifts in its clinical application. Coagulation abnormalities, which are prevalent complications in CAR-T-cell therapy, can range in severity from simple abnormalities in coagulation parameters to serious haemorrhage or disseminated intravascular coagulation associated with life-threatening multiorgan dysfunction. Nonetheless, there is a lack of a comprehensive overview concerning the coagulation abnormalities associated with CAR-T-cell therapy. With an aim to attract heightened clinical focus and to enhance the safety of CAR-T-cell therapy, this review presents the characteristics of the coagulation abnormalities associated with CAR-T-cell therapy, including clinical manifestations, coagulation parameters, pathogenesis, risk factors and their influence on treatment efficacy in patients receiving CAR-T-cell infusion. Due to limited data, these conclusions may undergo changes as more experience accumulates.

Tackling a deadly global phenomenon: sepsis induced coagulopathy: A narrative review.

Sepsis is a potentially fatal illness marked by organ failure and the two main causes of which are shock and disseminated intravascular coagulation. Multi-organ dysfunction in sepsis is mediated by the inflammatory cytokine storm, while sepsis induced coagulopathy is mediated and accelerated by activation of pro-coagulative mechanisms. Regardless of the severity of sepsis, disseminated intravascular coagulation is a potent predictor of mortality in septic patients. Additionally, oxidative stress in sepsis causes renal ischaemia and eventually acute kidney injury. The first and foremost goal is to initiate resuscitation immediately, with treatment mainly focussing on maintaining a balance of coagulants and anticoagulants. A simpler and more universal diagnostic criteria is likely to improve studies on the spectrum associated with sepsis.

Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Polytrauma in Children.

BACKGROUND: Inadequate clinical experience still causes uncertainty in the acute diagnostic evaluation and treatment of polytrauma in children (with or without coagulopathy). This review deals with the main aspects of the acute care of severely injured children in the light of current guidelines and other relevant literature, in particular airway control, volume and coagulation management, acute diagnostic imaging, and blood coagulation studies in the shock room. METHODS: This review is based on literature retrieved by a selective search in PubMed, Medline (OVIDSP), the Cochrane Central Register of Controlled Trials, and Epistemonikos covering the period January 2001 to August 2023. Review articles and the updated S2k clinical practice guideline on polytrauma management in childhood were considered. RESULTS: Most accidents in childhood occur at home and in the child's free time, with varying mechanisms and patterns of injury depending on age. The outcome of treatment depends largely on the presence or absence or traumatic brain injury, which affects 66% of children with polytrauma and is thus the most common type of injury in this group, and of hemorrhagic shock with or without coagulopathy. Acute care follows the ABCDE algorithms with attention to special features in children, including age-specific reference values. According to a registry study, coagulopathy and hypovolemic shock are associated with 22% and 17% mortality, respec - tively. Treatment in a pediatric trauma reference center of the trauma network is recommended. Computed tomography (CT) should be carried out in children in accordance with defined criteria (PECARN), as a team decision and with the use of age-specific low-dose CT protocols. In children as in adults, viscoelasticity-based point-of-care tests enable the prompt diagnosis of relevant coagulopathies and their treatment in consideration of age-specific target values. The administration of tranexamic acid remains controversial. CONCLUSION: 4% of polytrauma patients are children. Because children differ from adults both anatomically and physiologically, the diagnostic evaluation and management of polytrauma in children presents a special challenge. The evidence base for pediatric polytrauma management is still inadequate; current recommendations are based on consensus, in consideration of the special features of children compared to adults.

The role of viscoelastic hemostatic assays for postpartum hemorrhage management and bedside intrapartum care.

Viscoelastic hemostatic assays are point-of-care devices that assess coagulation and fibrinolysis in whole blood samples. These technologies provide numeric and visual information of clot initiation, clot strength, and clot lysis under low-shear conditions, and have been used in a variety of clinical settings and subpopulations, including trauma, cardiac surgery, and obstetrics. Emerging data indicate that these devices are useful for detecting important coagulation defects during major postpartum hemorrhage (especially low plasma fibrinogen concentration [hypofibrinogenemia]) and informing clinical decision-making for blood product use. Data from observational studies suggest that, compared with traditional formulaic approaches to transfusion management, targeted or goal-directed transfusion approaches using data from viscoelastic hemostatic assays are associated with reduced hemorrhage-related morbidity and lower blood product requirement. Viscoelastic hemostatic assays can also be used to identify and treat coagulation defects in patients with inherited or acquired coagulation disorders, such as factor XI deficiency or immune-mediated thrombocytopenia, and to assess hemostatic profiles of patients prescribed anticoagulant medications to mitigate the risk of epidural hematoma after neuraxial anesthesia and postpartum hemorrhage after delivery.

Bleeding complications, coagulation disorders, and their management in acute myocardial infarction-related cardiogenic shock rescued by veno-arterial ECMO: A retrospective cohort study.

PURPOSE: Management of dual antiplatelet therapy (DAPT) in patients on venoarterial-extracorporeal membrane (VA-ECMO) after acute myocardial infarction (AMI) is challenging. Our objective was to describe the frequency, management and outcomes of severe bleeding complications and determine their occurrence risk factors. MATERIAL AND METHODS: We conducted a retrospective observational cohort study including post-AMI cardiogenic shock patients requiring VA-ECMO. Severe bleeding was defined based on the Bleeding Academic Research Consortium classification. We calculated multivariable Fine-Gray models to assess factors associated with risk of severe bleeding. RESULTS: From January 2015 to July 2019, 176 patients received VA-ECMO after AMI and 132 patients were included. Sixty-five (49%) patients died. Severe bleeding occurred in 39% of cases. Severe thrombocytopenia (< 50 G/L) and hypofibrinogenemia (<1,5 g/L) occurred in respectively 31% and 19% of patients. DAPT was stopped in 32% of patients with a 6% rate of stent thrombosis. Anticoagulation was stopped in 39% of patients. Using a multivariate competing risk model, female sex, time on ECMO, troponin at admission and Impella® implantation were independently associated with severe bleeding. CONCLUSIONS: Bleeding complications and coagulation disorders were frequent and severe in patients on VA-ECMO after AMI, leading of antiplatelet therapy withdrawal in one third of patients.

Accidental hypothermia in the largest emergency hospital in North-Eastern Romania.

INTRODUCTION: Accidental hypothermia (AH) presents a significant mortality risk, even in individuals with good health. Early recognition of the parameters associated with negative prognosis could save more lives. METHODS: This was a pilot, retrospective observational study, conducted in the largest Emergency Hospital in North Eastern Romania, which included all patients with AH (defined as body temperature below 35°C), hospitalized and treated in our hospital between 2019 and 2022. RESULTS: A total of 104 patients with AH were included in our study, 90 of whom had data collected and statistically analyzed. The clinical, biological, and therapeutic parameters associated with negative outcomes were represented by a reduced GCS score (p=0.024), diminished systolic and diastolic blood pressure (p=0.007 respectively, 0.013), decreased bicarbonate (p=0.043) and hemoglobin levels (p=0.002), the presence of coagulation disorders (p=0.007), as well as the need for administration of inotropic or vasopressor medications (p=0.04). CONCLUSION: In this pilot, retrospective, observational study, the negative outcomes observed in patients with AH hospitalized in the largest Emergency Hospital in North-Eastern Romania were associated with several clinical, biochemical, and therapeutic factors, which are easy to identify in clinical practice. Recognizing the significance of these associated factors empowers healthcare practitioners to intervene at an early stage to save more lives.

Resuscitation and Care in the Trauma Bay.

Start balanced resuscitation early (pre-hospital if possible), either in the form of whole blood or 1:1:1 ratio. Minimize resuscitation with crystalloid to minimize patient morbidity and mortality. Trauma-induced coagulopathy can be largely avoided with the use of balanced resuscitation, permissive hypotension, and minimized time to hemostasis. Using protocolized "triggers" for massive and ultramassive transfusion will assist in minimizing delays in transfusion of products, achieving balanced ratios, and avoiding trauma induced coagulopathy. Once "audible" bleeding has been addressed, further blood product resuscitation and adjunct replacement should be guided by viscoelastic testing. Early transfusion of whole blood can reduce patient morbidity, mortality, decreases donor exposure, and reduces nursing logistics during transfusions. Adjuncts to resuscitation should be guided by laboratory testing and carefully developed, institution-specific guidelines. These include empiric calcium replacement, tranexamic acid (or other anti-fibrinolytics), and fibrinogen supplementation.

Special Issue "COVID-19 Coagulopathy: Advances on Pathophysiology and Therapies".

The Special Issue on COVID-19 coagulopathy initiated one year ago aimed to shed light on the mechanisms underlying the changes in the coagulation status making SARS-CoV-2 infection such a tough adversary for every one of the medical specialties encountering it, along with overseeing the therapeutic applications derived from the current understanding of these mechanisms [...].

Four years into the pandemic, managing COVID-19 patients with acute coagulopathy: what have we learned?

Coagulopathy alongside micro- and macrovascular thrombotic events were frequent characteristics of patients presenting with acute COVID-19 during the initial stages of the pandemic. However, over the past 4 years, the incidence and manifestations of COVID-19-associated coagulopathy have changed due to immunity from natural infection and vaccination and the appearance of new SARS-CoV-2 variants. Diagnostic criteria and management strategies based on early experience and studies for COVID-19-associated coagulopathy thus require reevaluation. As many other infectious disease states are also associated with hemostatic dysfunction, the coagulopathy associated with COVID-19 may be compounded, especially throughout the winter months, in patients with diverse etiologies of COVID-19 and other infections. This commentary examines what we have learned about COVID-19-associated coagulopathy throughout the pandemic and how we might best prepare to mitigate the hemostatic consequences of emerging infection agents.

COMPREHENSIVE THERAPEUTIC EFFICACY ANALYSIS OF INTRAVENOUS IMMUNOGLOBULIN IN TREATING SEPSIS-INDUCED COAGULOPATHY: A SINGLE-CENTER, RETROSPECTIVE OBSERVATIONAL STUDY.

ABSTRACT: Objective : The aim of the study is to investigate the efficacy of intravenous immunoglobulin (IVIg) in treating sepsis-induced coagulopathy ( SIC ). Methods : A retrospective controlled analysis was conducted on 230 patients with SIC at Ganzhou People's Hospital from January 2016 to December 2022. All patients were screened using propensity score matching and treated according to the SSC2016 guidelines. Compared with the control group (n = 115), patients in the test group (n = 115) received IVIg (200 mg/kg.d) for 3 consecutive days after admission. The rating scales, coagulation function, survival, and treatment duration were evaluated. Results : On day 3 of treatment, both groups exhibited reduced platelet and thromboelastogram (TEG) maximum amplitude (MA) levels, with the control group showing a more significant decrease ( P < 0.05). By the fifth day, these levels had recovered in both groups. However, the test group experienced a significant increase by day 7 ( P < 0.05). Coagulation factors II and X began to increase on day 3, and normalization was significantly faster in the test group on day 5 ( P < 0.05). The levels of prothrombin time, international normalized ratio, activated partial thromboplastin time, d -dimer, fibrinogen, fibrin degradation products, TEG-R, and TEG-K exhibited a notable decline on day 3 and demonstrated significantly faster recovery on day 5 in the test group ( P < 0.05). In addition, both groups showed a reduction in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, disseminated intravascular coagulation, and lactate (LAC) levels on day 3, but the test group's scores decreased significantly more by day 7 ( P < 0.05). Within the test group, white blood cell count, C-reactive protein, procalcitonin, IL-6, and Tmax levels were lower ( P < 0.05). Furthermore, the test group demonstrated shorter duration for intensive care unit stay, mechanical ventilation, and continuous renal replacement therapy ( P < 0.05). No significant differences were observed in the duration of fever or vasoactive drug use between the groups. However, the log-rank method indicated a higher 28-day survival rate in the test group ( P < 0.05). Conclusion : IVIg can successfully increase platelet count and coagulation factors, correct coagulation disorders, enhance organ function, and reduce 28-day mortality in patients with SIC .

Guidelines in trauma-related bleeding and coagulopathy: an update.

PURPOSE OF REVIEW: The diagnosis and treatment of patients with severe traumatic bleeding and subsequent trauma-induced coagulopathy (TIC) is still inconsistent, although the implementation of standardized algorithms/treatment pathways was repeatedly linked to improved outcome. Various evidence-based guidelines for these patients now exist, three of which have recently been updated. RECENT FINDINGS: A synopsis of the three recently updated guidelines for diagnosis and treatment of seriously bleeding trauma patients with TIC is presented: (i) AWMF S3 guideline 'Polytrauma/Seriously Injured Patient Treatment' under the auspices of the German Society for Trauma Surgery; (ii) guideline of the European Society of Anesthesiology and Intensive Care (ESAIC) on the management of perioperative bleeding; and (iii) European guideline on the management of major bleeding and coagulopathy after trauma in its 6th edition (EU-Trauma). SUMMARY: Treatment of trauma-related bleeding begins at the scene with local compression, use of tourniquets and pelvic binders and rapid transport to a certified trauma centre. After arrival at the hospital, measures to record, monitor and support coagulation function should be initiated immediately. Surgical bleeding control is carried out according to 'damage control' principles. Modern coagulation management includes individualized treatment based on target values derived from point-of-care viscoelastic test procedures.