Coagulation Changes Research Articles

“TEG” talks: technology worth spreading?

“TEG” talks: technology worth spreading?

Hematological Alterations Associated with COVID-19 Severe

Since the onset of the COVID-19 pandemic in 2020, several studies have been relating the severity of the disease with hematological and coagulation changes besides a strong immune response. Understanding what these changes are, in addition to seeking predictive biomarkers of mortality, has become an essential task to help control and reduce the death rate during hospitalization of COVID-19 patients with a severe clinical conditions. The objective of this study was to evaluate the hematological alterations according to the clinical outcomes of COVID-19. Hematological alterations such as lymphopenia, leukocytosis, neutrophilia, and decrease in hemoglobin and red blood cells, in addition to a state of hypercoagulability and cytokine storm, have become the main alterations present in hospitalized patients with COVID-19. The initial identification of these abnormalities is useful for the early prognosis of individuals who may die during hospitalization and thus allow these patients to receive targeted support to improve their clinical condition.

Dexmedetomidine induced hypotension and hemostatic markers.

The hemostatic system undergoes extensive alterations following surgical trauma leading to a hypercoagulable state. We assessed and compared the changes in platelet aggregation, coagulation, and fibrinolysis status during normotensive and dexmedetomidine-induced hypotensive anesthesia in patients undergoing spine surgery. Sixty patients undergoing spine surgery were randomly allocated into two groups: normotensive and dexmedetomidine-induced hypotensive groups. Platelet aggregation was assessed preoperatively, 15 min after induction, 60 min, and 120 min after skin incision, at the end of surgery, 2 h and 24 h postoperatively. Prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count, antithrombin III, fibrinogen, and D-dimer levels were measured preoperatively, 2 h and 24 h postoperatively. Preoperative platelet aggregation (%) was comparable between both groups. Platelet aggregation significantly increased intraoperative at 120 min after skin incision and postoperatively in the normotensive group compared to the preoperative value (P < 0.05) but it was insignificantly decreased during the intraoperative induced hypotensive period in the dexmedetomidine-induced hypotensive group (P > 0.05). Postoperative PT, aPTT significantly increased and platelet count, and antithrombin III significantly decreased in the normotensive group compared to the preoperative value (P < 0.05) but they were not significantly changed in the hypotensive group (P > 0.05). Postoperative D-dimer significantly increased in the two groups compared to the preoperative value (P < 0.05). Intraoperative and postoperative platelet aggregation significantly increased in the normotensive group with significant alterations of the coagulation markers. Dexmedetomidine-induced hypotensive anesthesia prevented the increased platelet aggregation that occurred in the normotensive group with better preservation of platelet and coagulation factors.

Relationship to Bariatric Surgery and their Gastrointestinal Hormones: how we Weight Loss?

Obesity is a disease related to severe metabolic comorbidities due to the high accumulation of body fat. In the context of this pandemic, bariatric surgery is the most effective treatment for the long-term resolution of the disease, having both structural and anatomic and hormonal effects on the gastrointestinal tract. The hormones analyzed in this review are cholecystokinin, secrete, gastrin, glucagon-like peptide 1 (GLP-1), peptide YY, pancreatic polypeptide, leptin, adiponectin, ghrelin, glucose, cholesterol, gastric inhibitory peptide, insulin, and glucagon. After bariatric procedures, changes in vitamins and micronutrients are also observed, which can lead to anemia, changes in coagulation, bone metabolism, neurological, and immunological deficiencies.

Traumatic coagulopathy in the older patient: analysis of coagulation profiles from the Activation of Coagulation and Inflammation in Trauma-2 (ACIT-2) observational, multicenter study

BackgroundMost studies describing traumatic coagulopathy have used data from patient cohorts with an average age of between 35 and 45 years. The last 10 years has seen a steep increase in the number of patients admitted with significant injury and bleeding who are older than the age of 65 years. Many coagulation protein levels alter significantly with normal aging, and it is possible that traumatic coagulopathy has a different signature with age. ObjectivesThe aim of this study was to report the coagulation profiles, including standard and extended laboratory, as well as viscoelastic hemostatic assays, stratified according to age to explore age-related differences in hemostatic capability. MethodsIn total, 1576 patients were analyzed from 6 European level 1 trauma centers. ResultsAs age increased, there was evidence of higher fibrinogen, greater thrombin generation, greater clotting factor consumption, and greater activation of fibrinolysis. Despite this, shock and severe injury led to the same pattern of changes within age groups: lower procoagulant factors (including fibrinogen), increased fibrinolysis, and higher levels of activated protein C. Thromboelastography and rotational thromboelastometry tests detected traumatic coagulopathy with prolongation of R/clotting time and reductions in clot amplitudes in each age cohort. Advancing age strongly correlated with higher fibrinogen levels and greater fibrinolysis. ConclusionAge-related coagulation changes are evident in injured patients. Broadly, similar patterns of coagulation abnormalities are seen across age groups following severe injury/shock, but thresholds for single clotting factors differ. Age-related differences may need to be considered when clinical treatments (eg, transfusion therapy) are indicated.

Assessment of Factor V Gene G1691A Mutation (Factor V Leiden) among Chronic Hepatitis C Patients with Thrombocytopenia

Background: Factor V plays a crucial role in the coagulation process. Factor V Leiden (FVL) is considered a mutant form of factor V, which may contribute to blood vessel thrombosis. Also, Hepatitis C Virus (HCV) infection may exert some coagulation changes leading to Portal Vein Thrombosis (PVT). Thrombocytopenia in patients with chronic HCV infection constitutes a major challenge. Objective: This study aimed to investigate the incidence of FVL (factor V gene G1691A mutation) and its influence on coagulation among HCV chronically infected patients suffering from thrombocytopenia. Besides, it was designed to demonstrate the association of chronic HCV infection with coagulation disturbances in such patients. Methods: This study was conducted on blood samples of a total of 54 subjects (33 HCV chronically infected patients and 21 healthy controls). HCV chronically infected patients with thrombocytopenia (Platelet Count [PLC] below 150 thousand/microliter) were selected. Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPPT) were previously determined as coagulation parameters. Protein C and protein S antigens were determined by ELISA as coagulation-regulating (anticoagulants) parameters. All samples were investigated for the presence of FVL by real-time PCR. Results: PLC, PT, and protein C antigen showed highly significant differences (p &lt; 0.001) between controls (group 1) and HCV chronically infected patients (group 2). Likewise, a highly significant change (p = 0.006) was achieved for the protein S antigen. A non-significant change was detected for the incidence of FVL with a heterozygous pattern between controls (group 1) and HCV chronically infected patients (group 2). Additionally, non-significant changes were detected for all of the investigated coagulation and coagulation-regulating (anticoagulants) parameters between control subjects with negative FVL (subgroup 1) and others with positive FVL (subgroup 2). Similarly, non-significant changes for such parameters were recoded for HCV chronically infected patients with negative FVL (subgroup 3) and others with positive FVL (subgroup 4). Conclusion: Chronic HCV infection in the presence of thrombocytopenia is associated with coagulation disturbances. The incidence of FVL with its heterozygous pattern is unaffected by chronic HCV infection, and no association is shown with worsening of coagulation in chronic hepatitis C patients suffering from thrombocytopenia.

Early myocardial injury and coagulation activation in thoracoscopic left atrial appendage clipping.

Thoracoscopic left atrial appendage clipping as a new strategy for stroke prevention. This study was established to observe the changes in myocardial injury and coagulation during the perioperative to provide the basis for anticoagulation strategy. Fifty-two patients with nonvalvular atrial fibrillation who completed thoracoscopic left atrial appendage clipping alone and 52 matched controls with thoracoscopic lobectomy were included in the study. The changes in coagulation and myocardial enzyme during the perioperative period were compared by t-test or nonparametric test. Linear correlation analysis was performed on the trend changes of each indicator in the left atrial appendage clipping group. Compared with the control group, the postoperative cardiac troponin I level in the thoracoscopic left atrial appendage clip group was significantly higher than that before the operation; there was no significant difference in the increase of myoglobin between the two groups. In the coagulation function, there was no significant difference in the increase of fibrinogen between the two groups. Postoperative D-dimer and fibrin degradation products were significantly increased, especially the left atrial appendage clip group was significantly higher than the control group, and even showed a trend of secondary increase. Cardiac troponin I was positively correlated with C-reactive protein, fibrinogen and von Willebrand Factor activity, and the Spearman nonparametric correlation coefficients were 1, 0.829, and 0.829, respectively (all p < .05). Thoracoscopic left atrial appendage closure surgery presents early myocardial injury and activation of coagulation function. The secondary increase of coagulation index needs our attention.

Admission maximum amplitude-reaction time ratio: Association between thromboelastography values predicts poor outcome in injured children.

Thromboelastography (TEG)-derived maximum amplitude-reaction time (MA-R) ratio that accounts for both hypocoagulable and hypercoagulable changes in coagulation is associated with poor outcomes in adults. The relationship between these TEG values and outcomes has not been studied in children. In a retrospective cohort study, a level I pediatric trauma center database was queried for children younger than 18 years who had a TEG assay on admission between 2016 and 2020. Demographics, injury characteristics, and admission TEG values were recorded. The MA-R ratio was calculated and divided into quartiles. Main outcomes included mortality, transfusion within 24 hours of admission, and thromboembolism. A logistic regression model was generated adjusting for age, Injury Severity Score, injury mechanism, admission shock, and Glasgow Coma Scale. In total, 657 children were included, of which 70% were male and 75% had blunt mechanism injury. The median (interquartile range) age was 11 (4-14) years, the median (interquartile range) Injury Severity Score was10 (5-22), and in-hospital mortality was 7% (n = 45). Of these patients, 17% (n = 112) required transfusion. Most R and MA values were within normal limits. On unadjusted analysis, the lowest MA-R ratio quartile was associated with increased mortality (15% vs. 4%, 5%, and 4%, respectively; p < 0.001) and increased transfusion need (26% vs. 12%, 16%, and 13%, respectively; p = 0.002) compared with higher quartiles. In the logistic regression models, a low MA-R ratio was independently associated with increased in-hospital mortality (odds ratio [95% confidence interval], 4.4 [1.9-10.2]) and increased need for transfusion within 24 hours of admission (odds ratio [95% confidence interval], 2.0 [1.2-3.4]) compared with higher MA-R ratio. There was no association between MA-R ratio and venous thromboembolic events (venous thromboembolic event rate by quartile: 4%, 2%, 1%, and 3%). Although individual admission TEG values are not commonly substantially deranged in injured children, the MA-R ratio is an independent predictor of poor outcome. Maximum amplitude-reaction time ratio may be a useful prognostic tool in pediatric trauma; validation is necessary. Therapeutic/Care Management; Level III.

Lipidomic signatures align with inflammatory patterns and outcomes in critical illness

Alterations in lipid metabolism have the potential to be markers as well as drivers of pathobiology of acute critical illness. Here, we took advantage of the temporal precision offered by trauma as a common cause of critical illness to identify the dynamic patterns in the circulating lipidome in critically ill humans. The major findings include an early loss of all classes of circulating lipids followed by a delayed and selective lipogenesis in patients destined to remain critically ill. The previously reported survival benefit of early thawed plasma administration was associated with preserved lipid levels that related to favorable changes in coagulation and inflammation biomarkers in causal modelling. Phosphatidylethanolamines (PE) were elevated in patients with persistent critical illness and PE levels were prognostic for worse outcomes not only in trauma but also severe COVID-19 patients. Here we show selective rise in systemic PE as a common prognostic feature of critical illness.

Thromboelastometry analysis of the heparin-like effect in the intra-operative period of orthotopic liver transplantation: An observational clinical trial

Introduction: Orthotopic liver transplant (OLT) can be followed by significant coagulopathy and the heparin-like effect (HLE). However, as the HLE may lead to important changes in blood coagulation, the objective of this study was to assess the prevalence of HLE in a cohort of patients undergoing liver transplantation. Materials and methods: This was a observational study including 50 patients ≥ 18 years of age who were submitted to OLT and monitored using ROTEM® delta, including 36 patients with altered INTEM coagulation time (CT) and 14 patients with normal INTEM CT. Samples were collected during the procedure to analyse the HLE. Results: Mild to moderate HLE was observed in 34% (17/50) of patients during surgery. Severe HLE was observed 10% (5/50) during surgery. Total 1-year survival was 80% (40/50) and mortality, 20% (10/50) (4% (2/5) with severe HLE in at NP; 5.9% (1/17) with mild/ moderate HLE in OS and in at NP, respectively, and in 11.8% (2/17) at AP, died 1-month postoperative). The transfusion of patients with severe HLE was (median [IQR]: red blood cells 3 [0.5-9.2] units), and those with mild/moderate HLE was (median [IQR]: red blood cells 1 [0.0 -2.0] and cryoprecipitate 10 [9.0-15.0] units). In the INTEM CT analysis, the average neohepatic phase (327.9 ± 161.1 s) was significantly prolonged when compared to OS (266.5 ± 134.4 s) and AP (253.02 ± 75.4 s); P = 0.013, respectively. Conclusion: The prevalence of HLE was considerable in neohepatic phase. In severe HLE, a high risk of mortality was identified in the neohepatic phase and a higher frequency of transfusion of red blood cells regardless of the surgical phase.

Changes in platelet function and coagulation after transcatheter aortic valve implantation evaluated with thromboelastography

IntroductionThe possibility of hypercoagulability during the perioperative period of transcatheter aortic valve implantation (TAVI) has been noted; however, there is still a controversy regarding the appropriate perioperative antithrombotic therapy. The...

Investigating the association between IL-6 antagonist therapy and blood coagulation in critically ill patients with COVID-19: a protocol for a prospective, observational, multicentre study

IntroductionHypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended...

Orthostatic Challenge-Induced Coagulation Activation in Young and Older Persons.

The incidence of thrombosis increases with aging. We investigated the coagulatory/haemostatic system across the ages and tested the hypothesis that older persons have a hypercoagulable state compared to younger persons at rest, and that standing up (orthostasis) leads to greater changes in coagulation in older persons. In total, 22 older and 20 young participants performed a 6 min sit-to-stand test (orthostatic challenge). Blood was collected prior to and at the end of standing and haemostatic profiling was performed via thrombelastometry (TEM), calibrated automated thrombogram (CAT) and standard coagulation assays. At baseline, three CAT-derived values indicated enhanced capability to generate thrombin in older participants. However, other measured parameters did not suggest a hypercoagulable state in older participants: prolonged TEM-derived coagulation times (295 vs. 209 s, medians, p = 0.0025) and prothrombin times (103 vs. 114%, medians, p = 0.0087), as well as lower TF levels (440 vs. 672 pg/mL, medians, p = 0.0245) and higher t-PA levels (7.3 vs. 3.8 ng/mL, medians, p = 0.0002), indicative of enhanced fibrinolytic capability, were seen. Younger participants were more sensitive to the orthostatic challenge: CAT-derived endogenous thrombin potentials (ETPs) were only increased in the young (1337 to 1350 nM.min, medians, p = 0.0264) and shortening of PTs was significantly higher in the young vs. older participants (p = 0.0242). Our data suggest that the increased thrombosis propensity in older persons is not primarily attributable to a hyperactive coagulation cascade but may be due to other pathologies associated with aging.

Platelet hemostasis in the implementation of placental dysfunction

The objective: to study the state of the platelet link of hemostasis in pregnant women with placental dysfunction. Materials and methods. A clinical and laboratory analysis of 54 patients with placental dysfunction was carried out. The control group included 30 practically healthy women with a physiological course of pregnancy. Venous blood of the patients was collected for testing using vacuum systems in tubes with 3.8% sodium citrate. The functional activity of platelets was studied on a photooptical aggregometer AP2110 (Solar, Belarus), thrombocytogram was performed on a hematological analyzer H18 LIGHT (SFRI SAS, France), thromboelastometric tests were determined on the ROTEM delta system (Tem Innovations GmbH, Germany). Results. Platelet hemostasis has a significant effect on maximum clot firmness (MCF) according to ROTEM results in patients with placental dysfunction. This indicator can be effective in determination of the hyperreactivity of the platelet unit in patients with placental dysfunction. Although no statically significant difference was found in the optical aggregometry indicators induced by ADP and collagen between the patients with placental dysfunction and the control group, a clear tendency to a sharp reduction in the lag-period of collagen-induced platelet aggregation in patients with placental dysfunction should be mentioned. Conclusions. Disorders in the platelet chain of hemostasis can play a significant role in the formation of a thrombophilic state in patients with placental dysfunction, as well as the damage of the endothelium and coagulation changes. The use of a test based on collagen-induced platelet aggregation may be a perspective method for effective diagnosis of platelet hyperreactivity. The study of the platelet link should become an additional element of the laboratory examination in order to resolve the issue of the need to prescribe antiplatelet agents to prevent the development of placental dysfunction.

Changes of Coagulation and Fibrinolytic Status Detected by Thromboelastography (TEG6s®) in Pregnancy, Labor, Early Postpartum, Postpartum Hemorrhage and Heparin Treatment for Perinatal Venous Thrombosis.

The aims of this study are to evaluate coagulation and fibrinolytic features using TEG6s® in normal pregnant courses, in the early postpartum period and in cases with postpartum hemorrhage (PPH) caused by uterine atony. We also analyze cases with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) under treatment with unfractionated heparin. The non-pregnant women (n = 13) and healthy pregnant women (at 9–13 weeks of gestation (n = 13), at 27–30 weeks of gestation (n = 14), at 35–38 weeks of gestation (n = 14)) were cross-sectionally studied, while the normal pregnant women at delivery (n = 14) were sequentially investigated. Blood samples from those patients with PPH (n = 15) and DVT and/or PE (n = 11) were also obtained and compared with those of normal women. Significant changes of clot formation parameters were observed in all parameters and, interestingly, fibrinolytic parameter (LY30) was maintained at a low value even within 120 min after placental delivery (median of LY30; 0) and also in cases with uterine atony (median of LY30; 0.1). The parameter that indicates the effectiveness of heparin showed strong correlation (R = 0.788) with activated partial thromboplastin time. Thromboelastography may be less sensitive to fibrinolysis in the conditions of uterine atonic bleeding.

ФАКТОРЫ РИСКА РАЗВИТИЯ ПАРОДОНТИТА У ПАЦИЕНТОВ В ПОСТКОВИДНЫЙ ПЕРИОД

Abstract. Introduction. According to independent epidemiological research of World Health Organization (WHO) intact periodontitis occurs only among 2-10% of the population, while inflammatory periodontal diseases are detected in 90- 95% of cases. The awareness of risk factors and their impact on periodontal diseases in somatic pathology allows not only to reduce the aggressiveness of disease development with the help of preventive measures, but also to predict possibilities of the main disease development. Aim. To identify the nature of periodontal microvasculature disorders among patients during post-covid period. Material and methods. We performed laboratory hematological examination, arterial blood oxygen level estimation, Doppler microcirculation study of periodontal tissues in patients diagnosed with B 34.2 «Coronavirus infection unspecified» COVID-19 of medium severity in hospital and in outpatient clinic after recovery. We conducted a questionnaire survey of patients «Subjective characteristic of the general state at the time of the disease outbreak», «Subjective characteristic of the state of the oral cavity in the aftercare period». Results and discussion. The Covid infection is associated with changes in the blood coagulation in conditions of persistent hypoxia, which is confirmed by all the stated methods of research. Complaints of varying degrees of severity about poor general well-being and changes in the oral cavity were noted in 100% of cases. No clinical manifestations of inflammation of periodontal tissues causing concern were found in patients in the post-occlusive period during the initial examination, but Doppler examination showed significant microcirculatory disorders. Conclusion. Laser Doppler flowmetry as an additional method of investigation reveals persistent microcirculatory disorders of periodontal tissues on the basis of extensive vascular endothelial damage in patients post COVID-19 which are not clinically manifested at this stage.

Changes in Coagulation and Platelet Reactivity in People with HIV-1 Switching Between Abacavir and Tenofovir

Background: Several studies have shown an association between abacavir (ABC) and increased risk of myocardial infarction (MI), but the causative mechanism has not been established. Both vascular endothelial inflammation and platelet activation have been proposed as contributing factors. Objective: The study aims to investigate the effects of ABC relative to tenofovir disoproxil (TDF) on functional assays of primary and secondary hemostasis and a comprehensible range of relevant biomarkers. Methods: In an investigator-initiated, open-labeled, crossover trial, we included HIV-infected males receiving either ABC or TDF and switched treatment to the alternate drug. At inclusion and after three months on the new regimen, we performed Multiplate® and thromboelastography (TEG®) and measured biomarkers of coagulation, inflammation, platelet reactivity, endothelial disruption and activation, and fibrinolysis, lipids, HIV RNA, CD4, CD8, and creatinine. Treatment effects were assessed by comparing intraindividual differences between the two treatment orders by the Wilcoxon Rank Sum test. Results: In total, 43 individuals completed the study. No intraindividual differences were observed for Multiplate® or TEG® when switching between regimens. We observed a significant treatment effect on coagulation factors II-VII-X (p&lt;0.0001), sCD40L (a biomarker of platelet reactivity, p=0.04), thrombomodulin (biomarker of endothelial damage, p=0.04), lipids, and CD8 cell counts (p=0.04), with higher values during ABC treatment compared to TDF. Conclusion: Compared to TDF, ABC treatment affected several outcome measures in a pro-coagulant direction. Suggesting that the risk of MI associated with ABC may be caused by the sum of multiple, discrete disturbances in the hemostatic system and endothelium. Study Registration: The trial was registered at clinicaltrials.gov (NCT02093585).

Indices of complement activation and coagulation changes in trauma patients

ObjectivesEarly complementopathy and coagulopathy are shown often after trauma. However, the prevalence of any interplay between complement cascade (ComC) and coagulation cascade (CoaC) after trauma remains unclear. This study intended...

Heparin therapy in COVID-19: Call for randomized controlled trials (RCTs).

Coronavirus disease 2019 (COVID-19) is associated with increases in abnormal coagulation, and particularly D-dimer (D-D) levels. Heparin therapy has been recommended as pharmacologic thromboprophylaxis in patients hospitalized with COVID-19; however, data on its efficacy are lacking. The current study retrospectively analyzed changes in blood coagulation and the impact of heparin therapy. Medical records of 593 patients with confirmed COVID-19 were collected. On admission, elevated fibrinogen (Fg) levels were noted in with 42.2% (250/593) of patients, followed by increases in D-D (28.5%) and a prolonged prothrombin time (PT) (23.9%). Patients with severe/critical COVID-19 had a higher proportion of abnormal coagulation parameters than patients with mild/ordinary COVID-19. Dynamic changes in coagulation parameters were plotted on timeline charts for 97 patients with COVID-19 after heparin treatment. These changes, when combined with Fg, PT, D-D, and other indicators, may provide a relatively comprehensive description of coagulation abnormalities. Heparin seems to be important in the treatment of patients with COVID-19 based on the current findings. The efficacy of heparin in the treatment of COVID-19 should be confirmed by randomized controlled trials (RCTs) as soon as possible.

Assessment of coagulation markers, serum zinc and copper in children with beta-thalassemia major in Egypt.

Thalassemia is one of the commonest single gene disorders usually associated with many complications. Coagulation changes as well as trace elements levels alterations have been described in children with β thalassemia. Activation of coagulation can be assessed by measuring thrombin-antithrombin (TAT) complex, plasmin-antiplasmin (PAP) complex and β-thromboglobulin (β-TG). A total of 200 children and adolescents were enrolled in the study; 100 were from the Al-Azhar University hospital's pediatric hematology clinic diagnosed as thalassemia major, while the other 100 were apparently healthy volunteers who acted as the control group. Complete blood count, liver function test, kidney function tests, TAT complex, PAP complex, β-TG as indicators of coagulation changes, serum zinc and copper were performed on all participants. Significantly higher levels of TAT complex, PAP complex and β-TG in thalassemia children than the controls. Decreased serum zinc and increased serum copper levels in thalassemia children compared to the controls. A negative correlation was observed between the serum level of TAT and hemoglobin level, besides the negative correlation of TAT complex and β-TG with the serum zinc. Thalassemia major was associated with increased serum level of coagulation activation markers, increased serum copper while decreased serum zinc.