Blood Coagulation Markers Research Articles

Impact of sample processing delays on plasma markers of inflammation, chemotaxis, cell death, and blood coagulation.

Biosampling studies in critically ill patients traditionally involve bedside collection of samples followed by local processing (ie. centrifugation, aliquotting, and freezing) and storage. However, community hospitals, which care for the majority of Canadian patients, often lack the infrastructure for local processing and storage of specimens. A potential solution is a "simplified" biosampling protocol whereby blood samples are collected at the bedside and then shipped to a central site for processing and storage. One potential limitation of this approach is that delayed processing may alter sample characteristics. To determine whether delays in blood sample processing affect the stability of cytokines (IL-6, TNF, IL-10, IFN-γ), chemokines (IL-8, IP-10, MCP-1, MCP-4, MIP-1α, MIP-1β), cell-free DNA (cfDNA) (released by dying cells), and blood clotting potential in human blood samples. Venous blood was collected into EDTA and citrate sample tubes and stored at room temperature (RT) or 4°C for progressive intervals up to 72 hours, prior to processing. Plasma cytokines and chemokines were quantified using single or multiplex immunoassays. cfDNA was measured using Picogreen DNA Quantification. Blood clotting potential was measured using a thrombin generation assay. Blood samples were collected from 9 intensive care unit (ICU) patients and 7 healthy volunteers. Admission diagnoses for the ICU patients included sepsis, trauma, ruptured abdominal aortic aneurysm, intracranial hemorrhage, gastrointestinal bleed, and hyperkalemia. After pre-processing delays of up to 72 hours at RT or 4°C, no significant changes were observed in plasma cytokines, chemokines, cfDNA, or thrombin formation. Delayed sample processing for up to 72 hours at either RT or 4°C did not significantly affect cytokines, chemokines, cfDNA, or blood clotting potential in plasma samples from healthy volunteers and ICU patients. A "simplified" biosampling protocol is a feasible solution for conducting biosampling research at hospitals without local processing capacity.

B-136 From Result to Response: The Development of Laboratory-Based Scoring Models to Predict COVID-19 Patient Outcomes

Abstract Background Patient characteristics relating to increased risk for COVID-19 severity are well-documented, including older age and pre-existing health concerns; however, methods to accurately predict patients’ acute reaction to SARS-CoV-2 infections remain lacking. Identification of specific laboratory tests informative of patient outcomes could effectively screen incoming patients and better inform physicians regarding optimal treatment plans. The aim of this study was to examine associations between frequently ordered laboratory markers and COVID-19 patient mortality to develop an objective laboratory-based scoring system that estimates patients’ risk of mortality. Methods Study participants included inpatients from 3 hospitals recruited into the GENCOV project based in Ontario, Canada. Participants (n=325) were at least 18 years of age, provided consent, and were hospitalized within 1 month of having a PCR confirmed COVID-19 infection between January 2020 and February 2022. Extensive clinical data including patient demographics, laboratory results, and treatment outcomes were extracted from patient’s electronic medical records (EMR). Results for 32 biochemical and hematological tests including complete blood cell counts, coagulation (activated partial thromboplastin time, D-dimer, fibrinogen, prothrombin time), general chemistry (albumin, blood gases, creatine kinase, electrolytes, glucose, triglycerides), inflammatory (lactate dehydrogenase, ferritin, C-reactive protein), liver (alanine aminotransferase, aspartate aminotransferase, total bilirubin), renal (creatinine, urea) and cardiac (troponin, NT-proBNP, BNP) markers were collected from each chart. Univariable logistic regression with nested likelihood ratio tests were used to determine significant associations between laboratory results and patient outcomes. Significant markers were incorporated into multivariable models and variable risk values were assigned. Total calculated risk scores for each participant were compared using univariable and multivariable risk values. Validation of each scoring method was performed on a 20% subset of inpatients. Receiver operating characteristic (ROC) curves evaluated model performance. Results Six laboratory markers were associated with COVID-19 patient mortality when controlling for age and sex. Univariable regression showed that elevated creatinine, elevated lactate, elevated white blood cell, low base excess, low bicarbonate, or low pH results upon admission were significantly associated with increased odds of mortality, in comparison to test results within the reference range for these same markers. Multivariable regression revealed fewer markers (only low bicarbonate and low base excess) showing significant associations with COVID-19 mortality. Area under the ROC curves (AUC) determined that risk scores derived from univariable values performed similarly to multivariable values in validation (0.800 vs 0.802) and development cohorts (0.821 vs 0.829). Total risk scores calculated from the univariable vs multivariable models suggest higher sensitivity (90% vs 85%) than specificity (58% vs 67%) in the validation cohort, whereas the development cohort had higher sensitivity (88%) than specificity (66%) with univariable scores, and higher specificity (81%) than sensitivity (74%) with multivariable scores. Conclusions Laboratory results associated with COVID-19 mortality following both univariable and multivariable analyses suggest hospitalized patients infected with SARS-CoV-2 may present with acidosis. Total risk scores derived from univariable and multivariable values performed similarly in predicting mortality; however, differences in marker significance between models indicate discrepancies with risk interpretation. Further comparison of the created risk score assessments with equivalent models in other populations is warranted.

Pulmonary Embolism Risk Assessment in Acute Isolated Distal Deep Venous Thrombosis.

The clinical risk factors and risk of developing pulmonary embolism (PE) in patients with acute isolated distal deep venous thrombosis (IDDVT) were assessed using single complete-duplex ultrasound (CDUS) imaging to reduce over-testing and over-treatment. This observational study was conducted from January 2020 to December 2022. Retrospective analysis was performed on CT pulmonary angiography (CTPA), blood coagulation markers, myocardial injury markers, blood gas analysis, and CDUS imaging of the lower extremity blood vessels of 146 patients with newly diagnosed IDDVT. Binary logistic regression was used to evaluate the relationship between these indicators and PE. After stepwise regression analysis, the predictors included in the regression model were D-dimer (DD), the sum of the thrombus length, and the maximum value of the thrombus width, with odds ratios (ORs) of 1.307 (p <0.001), 1.018 (p = 0.005), and 1.613 (p = 0.018), respectively. The combined prediction model achieved an area under the receiver operating characteristic curve (AUC) of 0.832 [95% confidence interval (CI): 0.761, 0.902]. By balancing the sensitivity and specificity of DD, combined single CDUS improves the predictive value for PE in patients with IDDVT. Key Words: Venous thrombosis, Pulmonary embolism, Ultrasonography, D-dimer, Diagnosis.

Impact of Estetrol Combined with Drospirenone on Blood Coagulation and Fibrinolysis in Patients with Endometriosis: A Multicenter, Randomized, Open-Label, Active-Controlled, Parallel-Group Study.

Venous thromboembolism is a serious safety concern in women using combined oral contraceptives; ethinyl estradiol (EE) is widely used as an estrogen. Estetrol (E4) is a native estrogen with selective tissue activity and exclusively produced by the fetal liver. This study used a multicenter, randomized, open-label, active-controlled, parallel-group design to evaluate the effects of E4 combined with drospirenone (DRSP) on coagulation and fibrinolysis in Japanese patients with endometriosis. Participants were randomized to receive either E4 15 mg/DRSP 3 mg or EE 20 µg/DRSP 3 mg for 12 weeks. E4/DRSP and EE/DRSP were administered orally once a day in a cyclic regimen, ie, 24-day active use followed by a 4-day hormone-free period, and a flexible extended regimen, respectively, and blood coagulation and fibrinolysis markers were measured. The effect on coagulation and fibrinolysis was considerably less in the E4/DRSP group than in the EE/DRSP group. Major anticoagulant proteins, protein S (free, total) and tissue factor pathway inhibitor (free), were reduced following EE/DRSP treatment. Consequently, thrombin generation determined by the activated protein C sensitivity ratio was increased by approximately 4-fold in the EE/DRSP group than in the E4/DRSP group. Eventually, the fibrinolysis cascade was triggered to compensate for disturbed coagulation, and D-dimer levels were 4.7-fold higher in the EE/DRSP group than in the E4/DRSP group. This study demonstrated that the effect of E4/DRSP on the blood coagulation and fibrinolysis cascades was significantly less than that of EE/DRSP in participants with endometriosis, a disease of women of advanced and reproductive age (jRCT2080225090, https://jrct.niph.go.jp/en-latest-detail/jRCT2080225090).

Identifying intense inflammatory subtype of esophageal squamous cell carcinoma using clustering approach.

To establish a risk-stratification system for predicting the postoperative recurrence of esophageal squamous cell carcinoma, this study aimed to evaluate the prognostic value of clusters based on blood inflammation and coagulation markers and investigate their correlation with serum cytokines and genetic alteration. This single-center, retrospective cohort study enrolled 491 patients with esophageal cancer who underwent subtotal esophagectomy between 2004 and 2012. For cluster exploration, nonhierarchical cluster analysis and k-means were applied using serum C-reactive protein, albumin, fibrinogen, and platelet-lymphocyte ratio as variables. Then, multivariate survival analysis was conducted to investigate the association of clusters with recurrence-free survival. To characterize the clusters, serum interleukin-6, interleukin-8, and genetic alteration in primary tumors, the PleSSision-Rapid panel, which can evaluate 160 representative driver genes, was used. Patients were classified into clusters 1, 2, and 3, which included 24 (5%), 161 (33%), and 306 (62%) patients, respectively. Compared with cluster 3, cluster 1 or 2 had significantly worse recurrence-free survival. Based on the multivariable analysis using cluster, pStage, and age as covariates, cluster was an independent prognostic factor for recurrence-free survival (hazard ratio, 1.55; 95% confidence interval, 1.08-2.21; P = 0.02). The percentage of serum interleukin-6 and interleukin-8 levels was the highest in cluster 1, followed by clusters 2 and 3. In 23 patients with available genomic profiles, no significant difference in representative genomic alterations was observed. Non-biased clustering using inflammation and coagulation markers identified the intense inflammatory subtype, which had an independent prognostic effect on recurrence-free survival.

Hepatitis E associated determinants and diagnostic biomarkers during pregnancy and its prenatal consequences in Multan, Punjab tertiary care setting (Pakistan).

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world. Hepatitis E infection is commonly widespread by the fecal oral routes and contaminated water. This study was designed to explore the prevalence and risk factors of hepatitis E infection in pregnant women of the Multan district, Pakistan. The study comprised of a total of 500 enrolled patients, among which, 105 pregnant females with hepatitis E infection fulfilled the criteria for anti-HEV antibodies. Pregnant women without significant complications and without hepatitis E infection were excluded from this study. Hepatic profile, complete blood count, coagulation markers, and standard protocol were also assessed for fetal maternal hemorrhage. Our results showed that 105 patients (66.66%, CI 95%) had HEV infection with mean age 25±5 years. Serum bilirubin levels were increased in 74 patients (70.47%), aspartate transaminase was elevated > 200 IU/L in 71 patients (67.61%), alanine transaminase was above the 100 IU/L in 65 patients (245 IU/L), and low platelet counts were found in 45 patients (42.85%). Moreover, fetal distress cases were 9 (10.84%) and maternal distress cases were about 11 (13.25%). Fetal mortality cases were 39 (37.14%), and maternal mortality cases were about 22 (20.95%) due to hepatic comma, intravascular coagulation, and hepatic failure. It was concluded that the prevalence of Hepatitis E during pregnancy is associated with high risk factors of unhygienic practices, blood transfusion, and noncompliance with universal infection control techniques. Maternal fatalities and fetal consequences were exacerbated by HEV infection.

Development of early prediction model of in-hospital cardiac arrest based on laboratory parameters

BackgroundIn-hospital cardiac arrest (IHCA) is an acute disease with a high fatality rate that burdens individuals, society, and the economy. This study aimed to develop a machine learning (ML) model using routine laboratory parameters to predict the risk of IHCA in rescue-treated patients.MethodsThis retrospective cohort study examined all rescue-treated patients hospitalized at the First Medical Center of the PLA General Hospital in Beijing, China, from January 2016 to December 2020. Five machine learning algorithms, including support vector machine, random forest, extra trees classifier (ETC), decision tree, and logistic regression algorithms, were trained to develop models for predicting IHCA. We included blood counts, biochemical markers, and coagulation markers in the model development. We validated model performance using fivefold cross-validation and used the SHapley Additive exPlanation (SHAP) for model interpretation.ResultsA total of 11,308 participants were included in the study, of which 7779 patients remained. Among these patients, 1796 (23.09%) cases of IHCA occurred. Among five machine learning models for predicting IHCA, the ETC algorithm exhibited better performance, with an AUC of 0.920, compared with the other four machine learning models in the fivefold cross-validation. The SHAP showed that the top ten factors accounting for cardiac arrest in rescue-treated patients are prothrombin activity, platelets, hemoglobin, N-terminal pro-brain natriuretic peptide, neutrophils, prothrombin time, serum albumin, sodium, activated partial thromboplastin time, and potassium.ConclusionsWe developed a reliable machine learning-derived model that integrates readily available laboratory parameters to predict IHCA in patients treated with rescue therapy.

Association between fatty liver index and blood coagulation markers: a population-based study

BackgroundPopulation-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population.MethodsAfter the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status.ResultsIn the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients.ConclusionIn this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.

Transient and fully reversible changes in laboratory parameters and modifications of the cytokine profile during blinatumomab treatment in children with relapsed or refractory B-cell acute lymphoblastic leukemia.

We analyzed changes in laboratory parameters, including blood counts, liver enzymes, inflammation and coagulation markers, and cytokines, from 70 blinatumomab-treated pediatric patients (NCT01471782). Overall, trends were consistent in responders and nonresponders. Platelets and lymphocytes peaked on day (D) 10 in cycle 1 and returned to baseline on D42 and D29, respectively. Neutrophils peaked on D2 and returned to baseline on D42. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin peaked on D17, reversing to baseline on D29; total protein levels were constant. These findings indicate that blinatumomab-induced changes in laboratory parameters were transient, reversible, and not requiring treatment interruptions in responders and nonresponders.

Clinical, Hematological, Biochemical and Radiological Characteristics for Patients With Splenic Infarction: Case Series With Literature Review.

Splenic infarction is a frequently missed diagnosis in acute clinical conditions and is often under-diagnosed due to the lack of high-quality evidence on pathophysiology of splenic infarction. Due to the scarcity of such evidence, no consensus guidelines regarding the diagnostic approach and management of patients with splenic infarction exist. Most of published articles on splenic infarction are case reports and there was no systematic review on splenic infarction. We conducted a retrospective analysis of all radiologically confirmed cases of splenic infarction patients with any history of admission at National Center for Global Health and Medicine Kohnodai Hospital, from 2014 to 2020. Further, to understand the pathophysiology that causes splenic infarction, we searched the literatures on splenic infarction. We found 18 patients with splenic infarction. The average age was 78 years, and about half of patients had abdominal pain; however, the other half did not have abdominal pain. One-third of patients with splenic infarction died. Leukocytosis with neutrophilia, a decrease of lymphocytes, anemia, hypoalbuminemia, and liver dysfunction were observed. Fibrinogen was decreased and D-dimer was remarkably elevated. Lactate dehydrogenase (LDH) and C-reactive protein (CRP) were remarkably increased. Six patients (33.3%) had cancer, four patients (22.2%) had atrial fibrillation, and four patients (22.2%) had infection. We found 466 case reports on splenic infarction published from 1975 to 2021. Recently, the number of case reports on splenic infarction due to infection, especially, coronavirus disease 2019 (COVID-19), has been remarkably increasing. Furthermore, we found that leukocytosis, a decrease of lymphocytes, elongated activated partial thromboplastin time, decrease of fibrinogen, liver dysfunction, elevation of LDH and blood urea nitrogen can be the prognosis predicting factors for patients with splenic infarction. Our study elucidated clinical, hematological, biochemical and radiological characteristics for patients with splenic infarction. We newly found significant differences in blood cell counts, coagulation markers, transaminases, LDH and blood urea nitrogen between patients who died and those who survived, suggesting that these parameters can be the prognosis predicting factors for splenic infarction. Further, our systematic review on case reports about splenic infarction showed the etiology of splenic infarction and the trend of the causative diseases.

Circadian rhythm and heart disease - what is the link? A review

Introduction and purpose: Cardiovascular disease (CVD) is still the leading cause of death worldwide and causes 49% of mortality in Europe. This makes CVD is the most important reason for premature mortality and Disability Adjusted Life Years (“DALYS”) in that continent. It is associated with variables such as blood pressure, heart rate, circulating catecholamines, markers of blood coagulation and vascular endothelial function which are dependent on different times of the day. The epidemiological data indicate that the biggest number of CVD incidents occur during the early morning hours. In this work we try to discuss the circadian rhythm and its impact on variables which, according to data, are most crucial on CV incident rate.&#x0D; Brief description of the state of knowledge: The cardiovascular disease and mortality risk is associated with variables such as morning blood pressure, fluctuations in metabolism rate or even in immunological response. These variables are dependent on the circadian rhythm. This article covers the most crucial components affected by the daily fluctuations considering the heart according to the literature from the last five years. &#x0D; Conclusions: This review highlighted the link between circadian rhythm and cardiovascular disease with the purpose of focusing on the most important clinically aspects of that machinery from blood pressure to inflammation. Despite all of these exciting findings which could possibly have future implications in the field of cardiology, there is still a significant need to explore this complicated relationship between the biological clock and the heart.

The antiplatelet activity of camel milk in healthy and aluminum chloride-intoxicated rats

This study examined the effect of camel milk on some marker of blood coagulation markers in aluminum chloride (ALCl3)-treated rats. Rats (n = 6) were assigned as control, control + fresh camel milk (1 ml), ALCl3 (0.5 mg/kg), and ALCl3 + fresh camel milk (1 ml and 0.5 mg/kg, respectively). Treatments were conducted orally for 30 days and daily. Administration of camel milk to control and ALCl3-intoxicated rats significantly increased platelet count, bleeding time, and collagen epinephrine (CEPI)-induced platelet aggregation. It also lowered plasma levels of thromboxane B2 and hepatic levels of glutathione (GSH) and the activities of antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD). While the treatment with camel milk has no effect on the liver structure, values of activated partial prothrombin time (aPPT), and levels of prothrombin time (PT) in control rats, it improved liver architectures and decreased serum levels alanine and aspartate aminotransferases (ALT and AST, respectively), and reduced values of both aPTT and PT in ALCl3-intoxicated rats. In conclusion, camel milk inhibits platelets activity and aggregation in both control and ALCl3-intoxicated rats.

PROTHROMBIN TIME, ACTIVATED PARTIAL THROMBOPLASTIN TIME AND PLATELET COUNT IN PATIENTS WITH DIABETES MELLITUS

Diabetes mellitus is a common disease in Libya, aimed to evaluate of Prothrombin Time, Activated Partial Thromboplastin Time and Thrombocytes among diabetic Patients and control . -This study includes 21 patients have diabetic and 49 persons as control. The blood coagulation markers, PT and aPTT were measured . Data analysis was performed using statistical package for social science (SPSS, version,22). Evaluation of patient’s data was performed using the t-test and Pearson correlation test. Results with p value &gt;0.05 were considered as statistically insignificant. The results showed the mean of PT in diabetes was 15.190 in patients when was 15.428 in control, when the mean of APTT was 29.76 in diabetic patients, when was 28.69 in control. The mean Platelet count cell ×(× 109 /L) , 269.90 in diabetic patients and in control was 294.35 . From the present study it may concluded that diabetes mellitus had no effects on PT and APTT. Routine examinations of PT, INR, APTT and Thrombocyte count are important to assess coagulation impairment among diabetic patients to prevent any thromboembolic complication.

Attempt for a Recombinant Thrombomodulin Alpha Treatment in a Rat Disseminated Intravascular Coagulation Model Using Yamakagashi (Rhabdophis tigrinus) Venom.

Yamakagashi (Rhabdophis tigrinus) inhabits Japan widely, and incidents involving its bites occur every year. Its bite causes disseminated intravascular coagulation when the amount of infused venom is high, and it can be fatal if treatment with Yamakagashi antivenom is delayed. Although Yamakagashi antivenom is used for treating Yamakagashi bites, it is an unapproved drug and its capacity for storage is limited. Hence, it is difficult to administer to patients promptly. As a therapeutic agent for this bite, we investigated the application of recombinant thrombomodulin alpha, a commercially available disseminated intravascular coagulation therapeutic agent. Its therapeutic effect on Yamakagashi venom was confirmed in a coagulation system of human plasma using in vitro Yamakagashi venom as well as a rat experimental model of disseminated intravascular coagulation using in vivo Yamakagashi venom. The administration of recombinant thrombomodulin alpha induced an effect that prolonged the blood coagulation time of Yamakagashi venom in vitro, and the drug was administered in vivo within 0.5 h after the administration of Yamakagashi venom to save rats. Blood coagulation markers such as platelet count, prothrombin time, fibrinogen concentration, and D-dimer levels recovered to normal values in rats. Therefore, recombinant thrombomodulin alpha may be used as a therapeutic agent for Yamakagashi bites.

Lysophosphatidic Acid Receptor 3 Suppress Neutrophil Extracellular Traps Production and Thrombosis During Sepsis.

Sepsis consists of life-threatening organ dysfunction resulting from a dysregulated response to infection. Recent studies have found that excessive neutrophil extracellular traps (NETs) contribute to the pathogenesis of sepsis, thereby increasing morbidity and mortality. Lysophosphatidic acid (LPA) is a small glycerophospholipid molecule that exerts multiple functions by binding to its receptors. Although LPA has been functionally identified to induce NETs, whether and how LPA receptors, especially lysophosphatidic acid receptor 3 (LPA3), play a role in the development of sepsis has never been explored. A comprehensive understanding of the impact of LPA3 on sepsis is essential for the development of medical therapy. After intraperitoneal injection of lipopolysaccharide (LPS), Lpar3 -/-mice showed a substantially higher mortality, more severe injury, and more fibrinogen content in the lungs than wild-type (WT) mice. The values of blood coagulation markers, plasma prothrombin time (PT) and fibrinogen (FIB), indicated that the Lpar3 -/- mice underwent a severe coagulation process, which resulted in increased thrombosis. The levels of NETs in Lpar3 -/- mice were higher than those in WT mice after LPS injection. The mortality rate and degree of lung damage in Lpar3 -/- mice with sepsis were significantly reduced after the destruction of NETs by DNaseI treatment. Furthermore, in vitro experiments with co-cultured monocytes and neutrophils demonstrated that monocytes from Lpar3 -/- mice promoted the formation of NETs, suggesting that LPA3 acting on monocytes inhibits the formation of NETs and plays a protective role in sepsis. Mechanistically, we found that the amount of CD14, an LPS co-receptor, expressed by monocytes in Lpar3 -/-mice was significantly elevated after LPS administration, and the MyD88-p65-NFκB signaling axis, downstream of toll-like receptor 4 signaling, in monocytes was overactivated. Finally, after an injection of the LPA3 agonist (2S)-1-oleoyl-2-methylglycero-3-phosphothionate (OMPT), the survival rate of mice with sepsis was improved, organ damage was reduced, and the production of NETs was decreased. This suggested the possible translational value and application prospects of (2S)-OMPT in the treatment of sepsis. Our study confirms an important protective role of LPA3 in curbing the development of sepsis by suppressing NETs production and thrombosis and provides new ideas for sepsis treatment strategies.

Changes in Procoagulant Blood Biomarkers After Mechanical Thrombectomy

ObjectivesThere is limited knowledge of the relationship between mechanical thrombectomy (MT) and endothelial inflammation in large-vessel occlusion (LVO) acute ischemic stroke (AIS). Intimal arterial damage releases tissue factor, a precipitant of the clotting cascade and thrombosis. We report changes in blood coagulation markers after MT treated with and without tissue plasminogen activator for AIS. Materials and MethodsCases of LVO-AIS treated with MT were included. Blood coagulation marker levels were measured within 10 h of stroke onset as a baseline and then 48 h later. Assayed biomarkers included: tissue factor procoagulant activity (TFPCA), factor VII (FVII), activated factor VII (FVIIa), factor VIII (FVIII), d-dimer, thrombin-antithrombin complex (TAT), plasminogen activator inhibitor-1 (PAI-1), and tissue factor pathway inhibitor (TFPI). Biomarker levels of MT with tissue plasminogen activator (TPA) or without (non-TPA) are reported. ResultsBiomarker levels from five patients with LVO-AIS treated with MT (three non-TPA, two TPA) were included. In non-TPA cases, TFPCA and PAI-1 increased while FVII, FVIIa, TAT, d-dimer, and TFPI decreased from baseline to 48 h. In TPA cases, TFPCA, FVIIa, d-dimer, TFPI, and PAI-1 decreased while FVIII increased from baseline to 48 h. ConclusionsTFPCA increased after MT in non-TPA but decreased in TPA treated patients. This finding suggests that MT is associated with elevated inflammation and procoagulation which may be reduced with TPA treatment. With further validation, the increase in TFPCA levels could help guide anticoagulant management of patients with MT without TPA.

A 3′ Untranslated Region Polymorphism of CTNNB1 (Rs2953) Alters MiR-3161 Binding and Affects the Risk of Ischemic Stroke and Coronary Artery Disease in Chinese Han Population

Background: CTNNB1 is reported to be related to the pathological process of ischemic stroke (IS) and coronary artery disease (CAD). Polymorphism located in the 3′ untranslated region (3′UTR) of a gene might affect gene expression by modifying binding sites for microRNAs (miRNAs). This study aimed to analyze the association between polymorphism rs2953, which locates in the 3′UTR of CTNNB1, and the risk of IS and CAD. Methods: The CTNNB1 messenger RNA (mRNA) expression level in peripheral venous blood was measured. In total, 533 patients with IS, 500 patients with CAD, and 531 healthy individuals were genotyped by Sequenom Mass­Array technology. The binding of miR-3161 to CTNNB1 was determined by dual-luciferase reporter assay. Results: The CTNNB1 mRNA expression level for the IS group was significantly lower than that for the control group. Rs2953 was significantly associated with both IS risk and CAD risk. Significant association was also found between polymorphism rs2953 and many conventional factors, such as serum lipid level, blood coagulation markers, blood glucose level, and homocysteine level in patients. Rs2953 T allele introduced a binding site to miRNA-3161 and thus decreased luciferase activity. Conclusion: Polymorphism rs2953 is associated with the risk of both IS and CAD. Moreover, polymorphism rs2953 (T) introduces a binding site to miRNA-3161 and thus decreases luciferase activity in cell lines.

Blood Coagulation Markers and Mechanical Thrombectomy

Online date: November 16, 2020 This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Immunity and coagulation and fibrinolytic processes may reduce the risk of severe illness in pregnant women with coronavirus disease 2019

BackgroundThere are specific physiological features regarding the immunity and coagulation among pregnant women, which may play important roles in the development of coronavirus disease 2019.ObjectiveThis study aimed to determine the key factors associated with the deterioration of patients with coronavirus disease 2019 and the differentiating clinical characteristics of pregnant women with coronavirus disease 2019 to interfere with the progression of coronavirus disease 2019.Study DesignA retrospective study of 539 Chinese Han adult patients with coronavirus disease 2019 was conducted, of which 36 cases were pregnant women. In addition, 36 pregnant women without coronavirus disease 2019 were recruited as the control. The characteristics of severe and critical illnesses, which were differentiated from mild and moderate illnesses in patients with coronavirus disease 2019, were analyzed using a machine learning algorithm. In addition, major differences between pregnant women with coronavirus disease 2019 and age-matched nonpregnant women with severe or critical coronavirus disease 2019, paired with pregnant women without coronavirus disease 2019, were explored to identify specific physiological features of pregnant women with coronavirus disease 2019.ResultsFor the total patient population, the lymphocyte, CD3+, CD4+, CD8+, CD19+, and CD16+CD56+ cell counts were significantly lower, and white blood cell count, neutrophil count, and neutrophil-to-lymphocyte ratio were higher in those with severe or critical illness than those with mild or moderate illness (P<.001). The plasma levels of interleukin-6, interleukin-10, and interleukin-6–to–interleukin-10 ratio were significantly increased in patients with critical illness compared with patients with mild, moderate, and severe illnesses (P<.001). The above immunologic coclusters achieved an area under the receiver operating characteristic curve of 0.801 (95% confidence interval, 0.764–0.838), and its combined model with the coagulation and fibrinolysis indices (prothrombin time, D-dimer) achieved an area under the receiver operating characteristic curve of 0.815 (95% confidence interval, 0.779–0.851) using the random forest regression model to predict severe or critical illness. For pregnant women with coronavirus disease 2019, none had preexisting diseases. Compared with nonpregnant women with mild or moderate coronavirus disease 2019, pregnant women with coronavirus disease 2019 displayed increased white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, and levels of D-dimer and fibrinogen, along with decreased lymphocyte and interleukin-4 levels (P<.05). Although they presented similar changes of immunologic markers of lymphocyte; white blood cell count; neutrophil-to-lymphocyte ratio; CD3+, CD4+, CD8+, and CD16+CD56+ cell counts; and interleukin-6–to–interleukin-10 ratio, compared with nonpregnant women with severe or critical coronavirus disease 2019, none of the pregnant women with coronavirus disease 2019 deteriorated into severe or critical illness. There was no significant difference in white blood cell count, lymphocyte count, neutrophil count, neutrophil-to-lymphocyte ratio, immunologic markers, or coagulation and fibrinolysis markers between pregnant women with coronavirus disease 2019 and pregnant women without coronavirus disease 2019. As for the discrepancy of pathophysiological features between pregnant women with coronavirus disease 2019 and nonpregnant women with severe or critical coronavirus disease 2019, the immunologic markers achieved an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.773–0.977), and its combined model with coagulation and fibrinolysis indices achieved an area under the receiver operating characteristic curve of 0.931 (95% confidence interval, 0.850–1.000).ConclusionImmune dysregulation was identified as a crucial feature of patients with coronavirus disease 2019, which developed severe or critical illness, and pregnant women with coronavirus disease 2019 presented with similar immune responses but rarer incidences of severe or critical illness. Immune dysregulation is related to the risks of deterioration into severe or critical illness. The specific coagulation and fibrinolysis systems of pregnancy may reduce the risk of pregnant women with coronavirus disease 2019 without preexisting disease from developing severe illness.

Bereavement in the year before a first myocardial infarction: Impact on prognosis.

Death of the spouse in middle and old age is associated with an increased risk of cardiovascular and total mortality, particularly during the months after the loss. Knowledge regarding the effect of bereavement on prognosis in acute myocardial infarction (AMI) is limited. We analysed whether bereavement the year before the AMI is associated with prognosis. We studied first AMI patients who participated in the Stockholm Heart Epidemiology Program (N = 1732). During or shortly after the hospitalization, patients or their family members completed a questionnaire regarding bereavement, sociodemographic, clinical and lifestyle factors; five months after their first infarction, surviving patients attended a clinical examination. Participants were followed for cardiovascular events and mortality for a median of 14 years. Overall bereavement, that is, death of a close friend or family member (including spouse/partner), the year before the first AMI was not associated with the combined outcome of non-fatal recurrent AMI and death due to ischaemic heart diseases. However, exposure to the loss of the spouse/partner was associated with an increased risk of the outcome (adjusted hazard ratio and (95% confidence interval): 1.55 (1.06-2.27)). We found no evidence that psychiatric disorders or blood lipids, glucose, coagulation and inflammatory markers mediated this association. Loss of spouse/partner the year before the first AMI was associated with an increased risk of the combination of non-fatal recurrent AMI and death due to ischaemic heart disease. If confirmed by others, the findings may be informative for tertiary prevention of AMI.