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.

Frequency, clinical, and laboratory findings of platelet secretion disorders in patients referred to the specialized coagulation laboratory of the Iranian Blood Transfusion Organization.

OBJECTIVES: Platelet secretion disorders (PSDs) are a subgroup of platelet function disorders (PFDs) caused by defects in the content or release of platelet granules. These patients have a variable degree of mucocutaneous bleeding tendency. The diagnostic facilities of PSDs are imitated in Iran, even in specialized coagulation laboratories. The present study aims to estimate the frequency of PSDs among patients referred to the Iranian Blood Transfusion Organization (IBTO). METHODS: The research population includes all patients referred to the specialized coagulation laboratory of IBTO and requested platelet function and von Willebrand testing by their physicians. They were recruited between May 2022 and October 2022 if they were not diagnosed as having procoagulant defects, von Willebrand disease (VWD), Glanzmann thrombasthenia (GT), Bernard-Soulier syndrome (BSS), and platelet count <100 × 10 9 (except in the syndromic forms). Patients with a defect in response to at least two agonists in Light transmission aggregometry (LTA), one agonist in the ATP-secretion study, and/or impairment in the expression of CD62P are considered PSDs. RESULTS: Among 121 cases referred to our center over 6 months, 40 patients fulfilled the inclusion and exclusion criteria. Ten patients were diagnosed with PSDs. Six were classified as δ-platelet secretion disorders (δ-PSD), two α-platelet secretion disorders (α-PSD), and two αδ-platelet secretion disorders (αδ-PSD). CONCLUSIONS: The prevalence of PSDs in our population study was 25% (10/40), which seems highly prevalent. Therefore, expanding laboratory approaches to platelet function defects is necessary as a routine in our country.

Assessment of rare bleeding disorders in adolescents with heavy menstrual bleeding.

INTRODUCTION: There are a significant number of patients with mucocutaneous bleeding, specifically heavy menstrual bleeding (HMB), who do not have a diagnosed bleeding disorder. These patients receive nontargeted interventions and may have suboptimal treatments. Functional assays, particularly for fibrinolytic and rare platelet function defects, are not robust and not readily available. AIM: We aimed to prospectively evaluate the prevalence of genetic defects associated with rare bleeding disorders and describe alterations of coagulation and fibrinolysis in a cohort of adolescents with HMB. METHODS: We performed a prospective observational cohort study of patients with HMB and unexplained bleeding. The study utilized a next generation sequencing panel and investigational global assays of coagulation and fibrinolysis. Additionally, specific functional assays were performed to help characterize novel variants that were identified. RESULTS: In 10 of the 17 patients (∼59%), genetic variants were identified on molecular testing. Thrombin generation by calibrated thromboelastography was not significantly altered in this patient population. The clot formation and lysis assay showed a trend towards increased fibrinolysis with rapid phase of decline in 23% of the patients. Further corresponding functional assays and study population are described. CONCLUSION: Our study describes a unique correlative model in a homogenous cohort of patients with HMB and unexplained bleeding which may inform future diagnostic algorithms, genotype-phenotype correlations as well as aid in specific targeted treatment approaches. Larger future studies may inform risk stratification of patients and improve health related outcomes in patients with HMB.

Pulmonary hypertension is associated with hypocoagulability in dogs: a retrospective analysis of 66 cases (2013-2021).

OBJECTIVE: To describe coagulation profiles in dogs with echocardiographic evidence of pulmonary hypertension (PH), to compare them to coagulation profiles in dogs without echocardiographic evidence of PH, and to determine the relationship between coagulation profiles and echocardiographic probability of PH. ANIMALS: 66 dogs with PH (cases) and 86 dogs without PH (controls). METHODS: Retrospective evaluation of records between 2013 and 2021 of dogs that had both an echocardiogram and a coagulation panel performed within 7 days. Dogs that received antithrombotics within 7 days of evaluation and dogs diagnosed with congenital or acquired coagulopathy or other severe systemic disease that could lead to coagulopathy were excluded. Dogs with a low echocardiographic probability of PH were also excluded. The dogs were divided into a PH group and non-PH group based on echocardiographic results. Demographic, clinicopathologic, and traditional coagulation parameters and VCM Vet (Entegrion) parameters were compared between the 2 groups. RESULTS: Dogs with PH were significantly older (median, 11 years vs 9.5 years, P = .02) and had a significantly lower body weight (median, 7.3 kg vs 19.3 kg, P < .001) than controls. Dogs with PH also had a significantly greater percent increase in prothrombin time (PT; P = .02), partial thromboplastin time (PTT; P < .0001), and fibrinogen (P = .045); however, their antithrombin concentration was lower (P = .005) compared to controls. Eight of 65 dogs (12.3%) in the PH group and 1/86 (1.2%) dogs in the non-PH group had an elevation of PT and/or PTT greater than 50% above the reference interval (P = .005). Dogs with PH had 11.9 times (95% CI, 1.5 to 97.9; P = .02) greater odds of being hypocoagulable than dogs without PH based on PT and PTT. CLINICAL RELEVANCE: This study demonstrated an association between a moderate to high echocardiographic probability of PH and a hypocoagulable state in dogs as determined by traditional coagulation assays. It underscores the importance of monitoring the coagulation status in canine patients with PH, particularly before initiating antithrombotic medications.

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.

Massive transfusion in trauma.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of currently recommended treatment approaches for traumatic hemorrhage shock, with a special focus on massive transfusion. RECENT FINDINGS: Severe trauma patients require massive transfusion, but consensual international definitions for traumatic hemorrhage shock and massive transfusion are missing. Current literature defines a massive transfusion as transfusion of a minimum of 3-4 packed red blood cells within 1 h. Using standard laboratory and/or viscoelastic tests, earliest diagnosis and treatment should focus on trauma-induced coagulopathy and substitution of substantiated deficiencies. SUMMARY: To initiate therapy immediately massive transfusion protocols are helpful focusing on early hemorrhage control using hemostatic dressing and tourniquets, correction of metabolic derangements to decrease coagulopathy and substitution according to viscoelastic assays and blood gases analysis with tranexamic acid, fibrinogen concentrate, red blood cells, plasma and platelets are recommended. Alternatively, the use of whole blood is possible. If needed, further support using prothrombin complex, factor XIII or desmopressin is suggested.

Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies.

Physiological hemostasis is a balance between pro- and anticoagulant pathways, and in sepsis, this equilibrium is disturbed, resulting in systemic thrombin generation, impaired anticoagulant activity, and suppression of fibrinolysis, a condition termed sepsis-induced coagulopathy (SIC). SIC is a common complication, being present in 24% of patients with sepsis and 66% of patients with septic shock, and is often associated with poor clinical outcomes and high mortality. 1 , 2 Recent preclinical and clinical studies have generated new insights into the molecular pathogenesis of SIC. In this article, we analyze the complex pathophysiology of SIC with a focus on the role of procoagulant innate immune signaling in hemostatic activation--tissue factor production, thrombin generation, endotheliopathy, and impaired antithrombotic functions. We also review clinical presentations of SIC, the diagnostic scoring system and laboratory tests, the current standard of care, and clinical trials evaluating the efficacies of anticoagulant therapies.

Contemporary management of major haemorrhage in critical care.

Haemorrhagic shock is frequent in critical care settings and responsible for a high mortality rate due to multiple organ dysfunction and coagulopathy. The management of critically ill patients with bleeding and shock is complex, and treatment of these patients must be rapid and definitive. The administration of large volumes of blood components leads to major physiological alterations which must be mitigated during and after bleeding. Early recognition of bleeding and coagulopathy, understanding the underlying pathophysiology related to specific disease states, and the development of individualised management protocols are important for optimal outcomes. This review describes the contemporary understanding of the pathophysiology of various types of coagulopathic bleeding; the diagnosis and management of critically ill bleeding patients, including major haemorrhage protocols and post-transfusion management; and finally highlights recent areas of opportunity to better understand optimal management strategies for managing bleeding in the intensive care unit (ICU).

Exploration of rotational thromboelastometry (ROTEM) to characterize the coagulation profiles of newly diagnosed pediatric leukemia patients.

BACKGROUND: Viscoelastic testing has been used in adult hematologic malignancies in conjunction with conventional coagulation tests (CCTs) to predict coagulopathies and tailor blood product replacement. However, there is a paucity of similar pediatric studies. OBJECTIVES: Analyze and correlate leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCT's and Rotational Thromboelastometry (ROTEM). METHODS: Pediatric patients with newly diagnosed acute leukemia underwent testing with ROTEM and CCTs on days 0, 15 and 29 of induction chemotherapy. RESULTS: Sixty-two patients were enrolled. At presentation, 54.8 % of patients had platelets <50 K/µL, 73 % had prolonged PT, 1.6 % had fibrinogen <150 mg/dL. Fifteen patients (24.2 %) had WHO grade 1 bleeding and two patients (3 %) had WHO grade 4 bleeding. EXTEM/INTEM values at presentation (day 0) reflected hypocoagulability, however FIBTEM revealed hypercoagulability. Patients showed a progressive hypocoagulability in all ROTEM assays by day 15 (day 0 vs day 15, p < 0.001), with improvement by day 29 (day 15 vs day 29, p < 0.001). Day 0 ROTEM parameters were comparable to day 29. Fibrinogen strongly correlated with ROTEM at all three time points (p < 0.0001), along with platelet count with moderate correlations (p < 0.001). CONCLUSION: Fibrinogen and platelets appear to be the drivers of leukemia associated coagulopathy in the pediatric population, suggesting the utility of using CCTs and ROTEM in this population to better evaluate hemostatic function and guide blood product replacement.

Detection of glycocalyx degradation in real time: A conceptual model of thromboelastography.

BACKGROUND: The endothelial glycocalyx is a critical component of the vascular barrier; its disruption after shock states may contribute to coagulopathy in a variety of conditions. Measurement of glycocalyx components in plasma have been used to index glycocalyx degradation but are not available as a point of care test. Heparanoids, such as heparan sulfate, may affect coagulation which may be detected by either thromboelastography or activated clotting time. METHODS: Endothelial glycocalyx components syndecan-1 and heparan sulfate were added to blood samples at clinically relevant concentrations. Thromboelastography values included clot reaction time, clot amplification and fibrinogen values, and maximum clot strength (maximum amplitude, platelets). The heparinase thromboelastography cartridge was used to detect a heparin-like effect. The activated clotting time test was performed subsequently using the heparan sulfate blood samples to compare a standard coagulation test with thromboelastography clot reaction times. RESULTS: Both thromboelastography clot reaction time (with comparison to heparinase) and activated clotting time were useful to detect effects of coagulation. Thromboelastography also detected platelet and fibrinogen abnormalities at higher heparan sulfate concentrations. Studies using thromboelastography or even activated clotting time may be useful to detect glycocalyx degradation after shock states and may guide clinical decision making. CONCLUSION: Thromboelastography and or activated clotting time may be useful to detect glycocalyx degradation as a point of care test in patients in the acute setting. Additionally, these assays may detect previous undisclosed coagulopathy due to glycocalyx degradation.

Trauma-induced coagulopathy: What you need to know.

ABSTRACT: Trauma-induced coagulopathy (TIC) is a global inflammatory state accompanied by coagulation derangements, acidemia, and hypothermia, which occurs after traumatic injury. It occurs in approximately 25% of severely injured patients, and its incidence is directly related to injury severity. The mechanism of TIC is multifaceted; proposed contributing factors include dysregulation of activated protein C, increased tPA, systemic endothelial activation, decreased fibrinogen, clotting factor consumption, and platelet dysfunction. Effects of TIC include systemic inflammation, coagulation derangements, acidemia, and hypothermia. Trauma-induced coagulopathy may be diagnosed by conventional coagulation tests including platelet count, Clauss assay, international normalized ratio, thrombin time, prothrombin time, and activated partial thromboplastin time; viscoelastic hemostatic assays such as thrombelastography and rotational thrombelastography; or a clinical scoring system known as the Trauma Induced Coagulopathy Clinical Score. Preventing TIC begins in the prehospital phase with early hemorrhage control, blood product resuscitation, and tranexamic acid therapy. Early administration of prothrombin complex concentrate is also being studied in the prehospital environment. The mainstays of TIC treatment include hemorrhage control, blood and component transfusions, and correction of abnormalities such as hypocalcemia, acidosis, and hypothermia. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Evaluation of coagulopathy in cirrhotic patients: A scoping review of the utility of viscoelastic testing.

BACKGROUND: Cirrhosis causes significant coagulopathy. Traditional coagulation tests may not accurately measure coagulopathy in well-compensated patients with cirrhosis. Viscoelastic tests are functional tests that may better assess coagulopathy in cirrhotic patients. METHODS: We searched PubMed, ScienceDirect, Google Scholar, and grey literature using terms meaning viscoelastic testing and cirrhosis. After reviewing over 500 titles and abstracts, 40 full-text papers met inclusion criteria. RESULTS: Twenty-two papers found viscoelastic testing was a better indicator of baseline coagulation than traditional testing in cirrhosis. Nineteen additional papers evaluated the utility of peri-procedural viscoelastic testing and found they led to a reduction in blood product administration without increasing risk of hemorrhage, thrombotic events, or other complications. CONCLUSIONS: The usage of viscoelastic testing in patients with cirrhosis allows for better assessment of coagulopathy, resulting in improved outcomes. Educating physicians to optimize care of this high-risk group is necessary to further improve their treatment.

How to assess hemostasis in patients with severe liver disease.

Patients with advanced liver diseases frequently acquire profound alterations in their hemostatic system. Simultaneous changes in procoagulant and anticoagulant systems result in a reset in the hemostatic balance with a relatively neutral net effect, although there are notable hypocoagulable and hypercoagulable features in the hemostatic system in patients with liver disease. Laboratory and clinical studies have demonstrated that patients have a relatively well-preserved hemostatic system even though routine diagnostic tests of hemostasis (prothrombin time, platelet count) suggest a bleeding tendency. Routine diagnostic tests of hemostasis are unsuitable to assess the hemostatic status of patients with liver disease, as these tests are insensitive for the concurrent prohemostatic and antihemostatic changes in these patients. These tests are, however, frequently requested in patients with liver disease, as they are well established indicators of severity of liver disease. This paper will discuss commonly used diagnostic and research-type hemostatic tests and will outline how test results should be interpreted in patients with liver disease.

[Value of the expression levels of complement-3a receptor 1 and neutrophil extracellular traps in predicting sepsis-induced coagulopathy]. / 外周血C3aR1及NETsè¡¨è¾¾æ°´å¹³å¯¹è„“æ¯’ç—‡æ€§å‡è¡€ç— çš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To investigate the clinical value of complement-3a receptor 1 (C3aR1) and neutrophil extracellular traps (NETs) in predicting sepsis-induced coagulopathy (SIC). METHODS: A prospective study was conducted among 78 children with sepsis who attended Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from June 2022 to June 2023. According to the presence or absence of SIC, they were divided into two groups: SIC (n=36) and non-SIC (n=42) . The two groups were compared in terms of clinical data and the levels of C3aR1 and NETs. The factors associated with the occurrence of SIC were analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the performance of C3aR1 and NETs in predicting SIC. RESULTS: Compared with the non-SIC group, the SIC group had significantly higher levels of C-reactive protein, interleukin-6 (IL-6), interleukin-10, C3aR1, and NETs (P<0.05). The multivaiate logistic regression analysis showed that the increases in C3aR1, NETs, and IL-6 were closely associated with the occurrence of SIC (P<0.05). The ROC curve analysis showed that C3aR1 combined with NETs had an area under the curve (AUC) of 0.913 in predicting SIC (P<0.05), which was significantly higher than the AUC of C3aR1 or IL-6 (P<0.05), while there was no significant difference in AUC between C3aR1 combined with NETs and NETs alone (P>0.05). CONCLUSIONS: There are significant increases in the expression levels of C3aR1 and NETs in the peripheral blood of children with SIC, and the expression levels of C3aR1 and NETs have a high clinical value in predicting SIC.

Viscoelastic Testing Methods.

Viscoelastic testing methods examine the real-time formation of a clot in a whole blood sample, and include thromboelastography (TEG), rotational thromboelastometry (ROTEM), and several other testing platforms. They allow for concurrent assessment of multiple aspects of clotting, including plasmatic coagulation factors, platelets, fibrinogen, and the fibrinolytic pathway. This testing is rapid and may be performed at the point-of-care, allowing for prompt identification of coagulopathies to guide focused and rational administration of blood products as well as the identification of anticoagulant effect. With recent industry progression towards user-friendly, cartridge-based, portable instruments, viscoelastic testing has emerged in the 21st century as a powerful tool to guide blood transfusions in the bleeding patient, and to identify and treat both bleeding and thrombotic conditions in many operative settings, including trauma surgery, liver transplant surgery, cardiac surgery, and obstetrics. In these settings, the use of transfusion algorithms guided by viscoelastic testing data has resulted in widespread improvements in patient blood management as well as modest improvements in select patient outcomes. To address the increasingly wide adoption of viscoelastic methods and the growing number of medical and laboratory personnel tasked with implementing, performing, and interpreting these methods, this chapter provides an overview of the history, physiology, and technology behind viscoelastic testing, as well as a practical review of its clinical utility and current evidence supporting its use. Also included is a review of testing limitations and the contextual role played by viscoelastic methods among all coagulation laboratory testing.

D-Dimer Elevation at Time of Admission is Associated with Need for Ventilator Support among Pediatric Patients with COVID-19 Infection.

BACKGROUND: This study aims to determine if coagulation abnormalities at presentation are associated with clinical severity of pediatric COVID-19 infection. METHODS: We retrospectively reviewed admission coagulation studies (D-dimer, prothrombin time (PT), partial thromboplastin time with hepzyme, fibrinogen, and platelet count) with disease severity defined by need for ICU admission, ventilator support, and length of stay (LOS). RESULTS: There were 110 pediatric patients (0.5 months to 18 years) who had coagulation studies collected within 24 hours of admission. Patients who required ICU admission and ventilation support had significantly higher D-dimer and PT values at presentation compared to patients who required neither. In addition, D-dimer showed moderate correlation with LOS. CONCLUSIONS: Elevated D-dimer correlated significantly with severity of disease and LOS, while prolonged PT only correlated with disease severity. Our data suggest that D-dimer at presentation may predict a pediatric patient's need for ICU care or ventilator support.

Point-of-care, goal-directed management of bleeding in trauma patients.

PURPOSE OF REVIEW: The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC). RECENT FINDINGS: Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders. Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies. Recent evidence has shown that viscoelastic tests (VETs) identify haemostatic disorders more rapidly and in more detail than SCTs. Moreover, VET results can guide coagulation therapy, allowing individualised treatment, which decreases transfusion requirements. However, the impact of VET on mortality remains uncertain. In contrast to VETs, the clinical impact of POC platelet function testing is still unproven. SUMMARY: POC SCTs are not able to characterise the complexity of trauma-associated coagulopathy. VETs provide a rapid estimation of underlying haemostatic disorders, thereby providing guidance for haemostatic therapy, which impacts allogenic blood transfusion requirements. The value of POC platelet function testing to identify platelet dysfunction and guide platelet transfusion is still uncertain.

Mechanisms and management of the coagulopathy of trauma and sepsis: trauma-induced coagulopathy, sepsis-induced coagulopathy, and disseminated intravascular coagulation.

Disseminated intravascular coagulation can occur due to different causes but commonly following sepsis. Trauma-induced coagulopathy (TIC) occurs on hospital arrival in approximately 25% of seriously injured patients who initially presents with impaired hemostasis and a bleeding phenotype that can later progress to a prothrombotic phase. Following traumatic injury, ineffective hemostasis is driven by massive blood loss, tissue damage, and hyperfibrinolysis. This initial impaired hemostasis continues until surgical or other management strategies not only to stop the causes of hemorrhage but also progresses to a prothrombotic and hypofibrinolytic state, also termed fibrinolytic shutdown. Prothrombotic progression is also promoted by inflammatory mediator release, endothelial injury, and platelet dysregulation, which is commonly seen in sepsis with increased mortality. Unlike TIC, the early phase of sepsis is frequently complicated by multiorgan dysfunction described as sepsis-induced coagulopathy (SIC) that lacks a hemorrhagic phase. The phenotypes of SIC and TIC are different, especially in their initial presentations; however, patients who survive TIC may also develop subsequent infections and potentially sepsis and SIC. Although the pathophysiology of SIC and TIC are different, endothelial injury, dysregulated fibrinolysis, and coagulation abnormalities are common. Management includes treatment of the underlying cause, tissue injury vs infection is critical, and supportive therapies, such as hemostatic resuscitation and circulatory support are essential, and adjunct therapies are recommended in guidelines. Based on clinical studies and certain guidelines, additional therapies include tranexamic acid in the limited timing of initial traumatic injury and anticoagulants, such as antithrombin and recombinant thrombomodulin in disseminated intravascular coagulation.