Acute Thrombotic Events Research Articles

Drug-Drug Interaction between Antiplatelet Therapy and Lipid-Lowering Agents (Statins and PCSK9 Inhibitors).

Lipid-lowering agents and antiplatelet drugs are guideline-recommended standard treatment for secondary prevention of acute thrombotic events in patients with increased cardiovascular risk. Aspirin is the most frequently used antiplatelet drug, either alone or in combination with other antiplatelet agents (P2Y12 inhibitors), while statins are first-line treatment of hypercholesterolemia. The well-established mode of action of aspirin is inhibition of platelet-dependent thromboxane formation. In addition, aspirin also improves endothelial oxygen defense via enhanced NO formation and inhibits thrombin formation. Low-dose aspirin exerts in addition anti-inflammatory effects, mainly via inhibition of platelet-initiated activation of white cells.Statins inhibit platelet function via reduction of circulating low-density lipoprotein-cholesterol (LDL-C) levels and a more direct inhibition of platelet function. This comprises inhibition of thromboxane formation via inhibition of platelet phospholipase A2 and inhibition of (ox)LDL-C-mediated increases in platelet reactivity via the (ox)LDL-C receptor (CD36). Furthermore, statins upregulate endothelial NO-synthase and improve endothelial oxygen defense by inhibition of NADPH-oxidase. PCSK9 antibodies target a serine protease (PCSK9), which promotes the degradation of the LDL-C receptor impacting on LDL-C plasma levels and (ox)LDL-C-receptor-mediated signaling in platelets similar to but more potent than statins.These functionally synergistic actions are the basis for numerous interactions between antiplatelet and these lipid-lowering drugs, which may, in summary, reduce the incidence of atherothrombotic vascular events.

TRATAMENTO CLÍNICO: PARA REDUÇÃO DE EVENTOS E NOVAS OPÇÕES

Drug therapy aimed at the treatment of coronary artery disease (CAD) or chronic coronary syndrome (CCS) is the most important step to be taken after establishing the diagnosis.It is the only therapy aimed at the disease itself and not just the lesions in isolation. The core of therapy, consisting of aspirin (ASA), statins, beta-blockers and angiotensin converting enzyme (ACE) inhibitors, has been consolidated over the last 40 years and is associated with a relative risk reduction of about 70% compared to the complete absence of treatment. Prevention of cardiovascular events targets acute myocardial infarction (AMI) and CAD-as-sociated death and focuses primarily on reducing the incidence of acute thrombotic events and the development of ventricular dysfunction. More recently, the concept of residual risk emerged, with therapies that can potentially reduce additional risk to the established the-rapy. Efforts directed at this residual cardiovascular risk focus on addressing inadequately reduced LDL cholesterol, systemic inflammation, high lipoprotein (a), hypertriglyceridemia, increased thrombotic risk, and other mechanisms.

COVID-19 Adenoviral Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT), COVID-19-Related Thrombosis, and the Thrombotic Thrombocytopenic Syndromes.

Adenoviral-based vaccines such as ChadoX1 CoV-19 (AstraZeneca) and Ad26.COV2.S (J&J) were developed to prevent infection and reduce hospitalization or death in Coronavirus Disease 2019 (COVID-19) patients. Although these vaccines passed safety and efficacy trials with excellent neutralizing capabilities against SARS-CoV-2, very rare reports of acute thrombotic thrombocytopenic events following administration emerged in certain populations, which triggered a series of clinical investigations that gave rise to a novel phenomenon called vaccine-induced immune thrombotic thrombocytopenia (VITT). Several converging pathways exist between VITT and other forms of thrombotic thrombocytopenic syndromes, specifically that of heparin-induced thrombocytopenia, which involves the formation of anti-PF4 antibodies and the activation of platelets leading to thrombocytopenia and thrombin-mediated clotting. Interestingly, certain differences in the presentation also exist in VITT, and guidelines have been published in recent months to assist clinicians in recognizing VITT to achieve desired outcomes. In this paper, we first discuss the clotting phenomenon in COVID-19 and delineate it from VITT, followed by a review of current knowledge on the clinical manifestations of VITT in lieu of other thrombotic thrombocytopenic syndromes. Likewise, emerging evidence on the role of adenoviral vectors and vaccine constituents is also discussed briefly.

EVALUATION OF THE IMPLEMENTATION OF ROTATIONAL THROMBOELASTOMETRY GUIDED COAGULATION MANAGEMENT IN ADULT CARDIAC SURGERY

<h3>Objective</h3> To evaluate changes in the administration of blood products and hemostatic drugs following the implementation of rotational thronboelastometry (ROTEM) in cardiac surgery in adult patients. To analyze changes in the rate of reintervention and perioperative complications. Economic analysis on the consumption of blood products, hemostatic drugs and ROTEM cartridges. <h3>Design and method</h3> Single-center retrospective cohort study. Exclusion criteria: interventions without cardiopulmonary bypass (CPB), emergent surgery, circulatory assist devices, heart transplant, ascending aortic dissection, Jehovah's Witness patients, congenital hemostasis disorders, and severe liver disease. In group 1 (before ROTEM), blood products and hemostatic drugs were administered empirically at the anesthesiologist's discretion. Activated clotting time, point-of-care prothrombin time testing, standard laboratory tests and clinical variables were used to guide therapeutic management. In group 2 (after ROTEM), blood products and hemostatic drugs were administered according to the Gorlinger algorithm modified. Variables preoperative period: age, sex, weight, height, BMI, BSA, hemoglobin level, number of platelets, creatinine, glomerular filtration rate, previous cardiac surgery. Variables intraoperative period: type of surgery, duration of CPB, administration of packed red blood cells (PRBC), platelet concentrates (PC), fresh frozen plasma (FFP), fibrinogen concentrate (FC), prothrombin complex concentrate (PCC) and rFVIIa. Variables postoperative period: reintervention (first 24h), mechanical ventilation >24h, acute lung injury (ALI), infection, thrombotic events, death, ICU and hospital length of stay. <h3>Results</h3> 759 patients were included, 438 in group 1 and 321 in group 2. There were no significant differences in age, sex, weight, height, BMI, BSA, preoperative anemia, thrombocytopenia, renal failure, previous cardiac surgery, type of surgey or interventions with CPB time >120 minutes. A significant reduction was observed in the number of patients who received PRBC (19% vs 29.2%; p = 0.001), FFP (1.6% vs 7.5%; p < 0.001), FC (23.4% vs 30.6%; p = 0.028) and rFVIIa (0.3% vs 2.7%; p = 0.011). A significant decrease was observed in the total quantity of PRBC, PC, FFP, FC and rFVIIa administered per patient. A significant reduction was observed in the incidence of postoperative infection (5.3% vs 10.3%; p = 0.013), ICU stay (median of 3 d vs 4 d; p < 0.001) and hospital stay (median of 8 d vs 11 d; p <0.001). There were no significant differences in the need for prolonged mechanical ventilation, surgical revision, incidence of ALI, thrombotic events or death. The economic analysis showed a total cost of 403,394.99 euros for group 1 and 203,292.97 euros for group 2. The average cost per patient was 921.00 euros in group 1 and 633.31 euros in group 2 (reduction of 30%). <h3>Conclusions</h3> Thromboelastometry reduces the administration of blood products and hemostatic drugs, in addition to lowering costs. The decreases in the incidence of infections and ICU and hospital stays cannot be solely attributed to the ROTEM technique as there are other factors that may have contributed.

Patterns of Direct Oral Anticoagulant Use in Pediatric Patients: Results from a Multicenter National Database

Introduction: The first direct oral anticoagulant (DOAC) agents were approved for pediatric use in 2021. These have quickly gained favor over traditional anticoagulants among many hematologists and patients due to oral availability, favorable risk profile, and elimination of the need for frequent lab monitoring. This study aims to evaluate trends in DOAC use among pediatric patients with new venous thrombotic events (VTE) and patient-level and hospital-level factors associated with their selection. Methods: This retrospective study used data from the Pediatric Health Information System (PHIS), an administrative database of >50 US children's hospitals. We included initial inpatient encounters from 2014-2021 for pediatric patients (age <18). The visit required an ICD9 or ICD10 code for an acute thrombotic event and medication charge for one of the following anticoagulation agents: dabigatran, edoxaban, rivaroxaban, apixaban, betrixaban, low molecular weight heparin (LMWH), or warfarin. We included only the first encounter for each patient which met these criteria. We compared characteristics of patients who received DOACs to those who did not through descriptive and statistical analysis, and utilized multivariate regression to evaluate factors associated with DOAC selection. Results: In 20,432 cases of new VTE, DOACs were administered in 733 encounters (3.59%). Rivaroxaban was the most administered (71.9% of DOAC use), followed by apixaban. DOAC use increased over time, it was prescribed in 0.24% of the encounters in 2014 up to 11.4% of the encounters in 2021. DOACs were first only administered to grade school age children (5-12 years) in 2016 and then moved to younger groups in 2019. Patients who received DOAC agents had a greater median age (16 vs 4 years, p<0.001), were more commonly female (51.7% vs 46.7%, p=0.008), had greater median income ($60,428 vs $55,089, p<0.001), and were more likely to carry private insurance (47.1% vs 40.6%, p=0.002). Geographic variation was also observed, with midwest hospitals prescribing DOACs more often than in the south and west (5.5% vs 2.8%). Patients who received DOACs during their admission had a shorter median duration of hospitalization, lower hospitalization costs, and were less likely to have a complex chronic condition (all comparisons were statistically significant). DOACs were most prescribed in cases of pulmonary embolism (8.2% of encounters carrying ICD code for pulmonary embolism). On multivariate regression analysis including age, gender, race, ethnicity, insurance payor, income, and geographic region, only age, income and geographic region remained statistically significant predictors of DOAC use (p<0.05). Conclusion: This abstract describes the increase in DOAC usage over time. The decision to prescribe a DOAC agent appears to be affected by patient age, medical co-morbidities and income. The data presented suggests the presence of prescription trends that may not be based on clinical evidence. A better understanding of the safety and efficacy of DOAC agents in pediatric patients and education of pediatric hematology providers is necessary. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk factors for ischemic cerebral stroke in patients with acute amaurosis fugax

ObjectifSelon la National Stroke Association et l'American Heart Association, l'ischémie rétinienne, comme celle qui se produit pendant une amaurose transitoire (AT), est une forme d'accident vasculaire cérébral (AVC). Notre étude visait à évaluer les facteurs de risque d'accident ischémique cérébral chez les patients hospitalisés en raison d'une AT aiguë. MéthodesOn a consulté la base de données NIS (National Inpatient Sample) pour recenser les patients d'au moins 21 ans qui avaient reçu un diagnostic primaire d'AT au moment de leur admission (code 362.34 de la neuvième édition de la classification internationale des maladies [ICD-9]) entre 2002 et 2014. Les mesures liées aux comorbidités et les incidents qui sont survenus pendant l'hospitalisation ont été recensés à l'aide des codes ICD-9 pertinents. On a eu recours au logiciel IBM SPSS 25 et au package R pour réaliser les analyses statistiques. RésultatsUn total pondéré de 12 142 patients a été identifié. Les troubles concomitants les plus fréquents au sein de cette cohorte présentant une AT comprenaient l'hypertension, la dyslipidémie, le tabagisme, la coronaropathie et le diabète de type 2. Selon l'analyse de régression multiple, certaines affections concomitantes – hypercoagulabilité, vascularite systémique, coronaropathie et athérosclérose – constituent des facteurs de risque indépendants d'accident ischémique cérébral en présence d'AT. En revanche, la dyslipidémie a été associée à une réduction du risque. Le risque était 5 fois plus élevé chez les Asiatiques et les personnes provenant des îles du Pacifique, comparativement aux Caucasiens. ConclusionOn a diagnostiqué un accident ischémique cérébral et un infarctus du myocarde chez 0,3 % à 0,9 % des patients hospitalisés en raison d'une AT aiguë. L'hypercoagulabilité, la vascularite systémique, la coronaropathie et l'athérosclérose étaient des facteurs de risque indépendants d'accident ischémique cérébral, chacun multipliant le risque par plus de 3. Les patients qui présentent ces facteurs de risque conjointement à une AT aiguë doivent faire l'objet d'une surveillance étroite en raison du risque de thrombose généralisée aiguë.

Defective efferocytosis of vascular cells in heart disease.

The efficient phagocytic clearance of dying cells and apoptotic cells is one of the processes that is essential for the maintenance of physiologic tissue function and homeostasis, which is termed “efferocytosis.” Under normal conditions, “find me” and “eat me” signals are released by apoptotic cells to stimulate the engulfment and efferocytosis of apoptotic cells. In contrast, abnormal efferocytosis is related to chronic and non-resolving inflammatory diseases such as atherosclerosis. In the initial steps of atherosclerotic lesion development, monocyte-derived macrophages display efficient efferocytosis that restricts plaque progression; however, this capacity is reduced in more advanced lesions. Macrophage reprogramming as a result of the accumulation of apoptotic cells and augmented inflammation accounts for this diminishment of efferocytosis. Furthermore, defective efferocytosis plays an important role in necrotic core formation, which triggers plaque rupture and acute thrombotic cardiovascular events. Recent publications have focused on the essential role of macrophage efferocytosis in cardiac pathophysiology and have pointed toward new therapeutic strategies to modulate macrophage efferocytosis for cardiac tissue repair. In this review, we discuss the molecular and cellular mechanisms that regulate efferocytosis in vascular cells, including macrophages and other phagocytic cells and detail how efferocytosis-related molecules contribute to the maintenance of vascular hemostasis and how defective efferocytosis leads to the formation and progression of atherosclerotic plaques.

Serial assessment of thrombogenicity and hemodynamics in patients with type II diabetes in a clinical research unit: Evidence for circadian variations in clot formation

Circadian fluctuations in thrombogenicity and hemostasis play a role in acute cardiovascular thrombotic events occurring in the early morning hours. There is a lack of data assessing thrombogenicity, platelet function, and hemodynamics to investigate diurnal variations in a high cardiovascular risk population. This was an exploratory, single-center study conducted in aspirin-treated patients with Type II Diabetes Mellitus (T2DM) (n = 37) with documented vascular disease and/or multiple cardiovascular risk factors. Hemodynamic monitoring and blood sample collection for thromboelastography (TEG) and platelet function testing were done serially at 7-9 AM (morning), 7-9 PM (evening), 11 PM-1 AM (night), and at 5-7 AM (awakening). R-value measured by TEG was shorter during awakening hours than during the night and day hours (p < 0.05). There were no changes in platelet reactivity in response to arachidonic acid, adenosine diphosphate, and collagen between time points. Pulse pressure (PP) was highest during awakening hours (p < 0.05). Study findings provide a mechanistic explanation for increased thrombotic events observed in the early waking hours among diabetics with multiple cardiovascular risk factors. The role of chronotherapy in reducing coagulability and PP to improve clinical outcomes should be explored.

Diagnostic and prognostic value of the ratio of mean platelet volume to platelet count in acute mesenteric ischemia

Introduction: Acute mesenteric ischemia (AMI) is a condition in which there is a sudden cessation of blood supply to a particular intestinal segment and consequent cellular damage. Although it has a low incidence of approximately 0.09-0.2% of all emergency surgery admissions, AMI is a severe condition that can cause high early mortality. A direct relationship between an increased mean platelet volume (MPV) and acute thrombotic events has been shown in recent years. we aimed to find out whether the diagnosis of mesenteric ischemia and the amount of bowel segment affected by ischemia will guide clinicians preoperatively with these markers&#x0D; Material and Method: A total of 57 cases with bowel resection due to mesenteric ischemia were included in the study. The gender, age, serum platelet (PLT), MPV, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), Albumin, CRP, neutrophil-lymphocyte ratio (NLR), MPV/Platelet Count, and CRP-albumin ratio (CAR) levels at the time of admission, operation time, length of resected bowel segment, length of hospital stay, presence of necrosis and perforation from pathology reports, and length of bowel segment leading to necrosis were scanned.&#x0D; Results: A moderate negative correlation was found between the length of resected bowel segment and PLT (P

Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an ad hoc expert panel.

The introduction of new therapeutic agents for multiple myeloma (MM), including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has improved the outcomes of patients but, in parallel, has changed the frequency and epidemiology of thrombotic events. Thrombosis is now a significant cause of morbidity and mortality in MM patients, and optimal thromboprophylaxis is far from being reached. Moving from the recognition that the above issue represents an unmet clinical need, an expert panel assessed the scientific literature and composed a framework of recommendations for improving thrombosis control in patients who are candidates for active treatment for MM. The panel generated key clinical questions using the criterion of clinical relevance through a Delphi process. It explored four domains, i.e., thrombotic risk factors and risk stratification, primary thromboprophylaxis, management of acute thrombotic events, and secondary thromboprophylaxis. The recommendations issued may assist hematologists in minimizing the risk of thrombosis and guarantee adherence to treatment in patients with MM who are candidates for active treatment.

Thrombo-Inflammation and Immunological Response in Ischemic Stroke: Focusing on Platelet-Tregs Interaction.

Strokes are mainly caused by thromboembolic obstruction of a major cerebral artery. Major clinical manifestations include paralysis hemiplegia, aphasia, memory, and learning disorders. In the case of ischemic stroke (IS), hyperactive platelets contribute to advancing an acute thrombotic event progression. Therefore, the principal goal of treatment is to recanalize the occluded vessel and restore cerebral blood flow by thrombolysis or mechanical thrombectomy. However, antiplatelets or thrombolytic therapy may increase the risk of bleeding. Beyond the involvement in thrombosis, platelets also contribute to the inflammatory process induced by cerebral ischemia. Platelet-mediated thrombosis and inflammation in IS lie primarily in the interaction of platelet receptors with endothelial cells and immune cells, including T-cells, monocytes/macrophages, and neutrophils. Following revascularization, intervention with conventional antiplatelet medicines such as aspirin or clopidogrel does not substantially diminish infarct development, most likely due to the limited effects on the thrombo-inflammation process. Emerging evidence has shown that T cells, especially regulatory T cells (Tregs), maintain immune homeostasis and suppress immune responses, playing a critical immunomodulatory role in ischemia-reperfusion injury. Hence, considering the deleterious effects of inflammatory and immune responses, there is an urgent need for more targeted agents to limit the thrombotic-inflammatory activity of platelets and minimize the risk of a cerebral hemorrhage. This review highlights the involvement of platelets in neuroinflammation and the evolving role of Tregs and platelets in IS. In response to all issues, preclinical and clinical strategies should generate more viable therapeutics for preventing and managing IS with immunotherapy targeting platelets and Tregs.

COVID-19-related thrombotic complications experience before and during delta wave.

ObjectiveHypercoagulability and thrombotic complications seen in SARS-CoV-2 patients, as well as the associated pathophysiology, have been reported extensively. However, there is limited information regarding the factors related to this phenomenon and its association with the COVID-19 delta variant.MethodsA retrospective review including patients admitted to a tertiary center with a COVID-19 positive test and at least one acute thrombotic event confirmed by imaging between June 2020 and August 2021 was performed. We compared the rates of thrombotic events in patients with COVID-19 before and during the Delta peak. We also analyzed the association of the thrombotic complications with demographic characteristics, comorbidities, anticoagulation strategies, and prothrombotic markers while describing other complications secondary to COVID-19 infection.ResultsOut of 964 patients admitted with COVID-19 diagnosis, 26.5% (n=256) had a thrombotic event evidenced by ultrasound (US) or computerized tomography (CT) scan. Venous thromboembolism was found in 60% (n=153), arterial thrombosis in 23% (n=60), and both venous and arterial thromboses in 17% (n=17) of the study cohort. Of all patients, 94% were not vaccinated. Delta variant wave patients (DW) had thrombotic episodes in 34.7% (n=50/144) of cases compared to 25% (n=206/820) of non-Delta wave (NDW) patients, posing an estimated risk 1.36 times higher in patients infected with COVID-19 during the DW than NDW. Overall, DW subjects were significantly younger (p<0.001) with lower BMI (p=0.021) compared to NDW patients. Statistical analyses showed African American patients were more likely to have arterial thrombosis compared to the other groups when testing positive for COVID-19 (OR: 1.78 [CI: 1.04 – 3.05], p=0.035), whereas immunosuppressed patients had less risk of arterial thrombosis (OR: 0.38 [CI: 0.15 – 0.96], p=0.042). Female gender (OR: 2.15 [CI: 1.20 – 3.85]. p=0.009) and patients with active malignancy (OR: 5.99 [CI: 2.14 – 16.78]. p=0.001) had an increased risk of having multiple thrombotic events at different locations secondary to COVID-19.ConclusionCOVID-19 infection is associated with elevated rates of thrombotic complications and an especially higher risk in patients infected during the Delta variant peak. We highlight the importance of vaccination and the development of new anticoagulation strategies for COVID-19 patients with additional hypercoagulable risk factors to prevent thrombotic complications caused by this disease.

Initiation of Tocilizumab or Baricitinib Were Associated With Comparable Clinical Outcomes Among Patients Hospitalized With COVID-19 and Treated With Dexamethasone.

Objectives: This retrospective cohort study aims to explore head-to-head clinical outcomes and complications associated with tocilizumab or baricitinib initiation among hospitalized COVID-19 patients receiving dexamethasone. Methods: Among 10,445 COVID-19 patients hospitalized between January 21st 2020 and January 31st 2021 in Hong Kong, patients who had received tocilizumab (n = 165) or baricitinib (n = 76) while on dexamethasone were included. Primary study outcome was time to clinical improvement (at least one score reduction on WHO clinical progression scale). Secondary outcomes were disease progression, viral dynamics, in-hospital death, hyperinflammatory syndrome, and COVID-19/treatment-related complications. Hazard ratios (HR) of event outcomes were estimated using Cox regression models. Results: The initiation of tocilizumab or baricitinib had no significant differences in time to clinical improvement (HR = 0.86, 95%CI 0.57-1.29, p = 0.459), hospital discharge (HR = 0.85, 95%CI 0.57-1.27, p = 0.418), recovery without the need for oxygen therapy (HR = 1.04, 95%CI 0.64-1.67, p = 0.883), low viral load (HR = 1.49, 95%CI 0.85-2.60, p = 0.162), and positive IgG antibody (HR = 0.97, 95%CI 0.61-1.54, p = 0.909). Time to viral clearance (HR = 1.94, 95%CI 1.01-3.73, p = 0.048) was shorter in the tocilizumab group with marginal significance, compared to that of baricitinib. Meanwhile, the two treatment modalities were not significantly different in their associated risks of in-hospital death (HR = 0.63, 95%CI 0.29-1.35, p = 0.233), severe liver injury (HR = 1.15, 95%CI 0.43-3.08, p = 0.778), acute renal failure (HR = 2.33, 95%CI 0.61-8.82, p = 0.213), hyperinflammatory syndrome (HR = 2.32, 95%CI 0.87-6.25, p = 0.091), thrombotic and bleeding events (HR = 1.39, 95%CI 0.32-6.00, p = 0.658), and secondary infection (HR = 2.97, 95%CI 0.62-14.31, p = 0.173). Conclusion: Among hospitalized patients with moderate-to-severe COVID-19 on background dexamethasone, the initiation of tocilizumab or baricitinib had generally comparable effects on time to clinical improvement, hospital discharge, recovery, low viral load, and positive IgG antibody; risks of in-hospital death, hepatic and renal complications, hyperinflammatory syndrome, thrombotic and bleeding events, and secondary infection. On the other hand, tocilizumab users might achieve viral clearance slightly faster than baricitinib users. Further studies and clinical trials are needed to confirm our findings regarding the evaluation of tocilizumab and baricitinib in COVID-19 patients with different disease severities, at varying stages or timing of drug initiation, and considering the concomitant use of other therapeutics.

Diagnostic and prognostic value of the ratio of mean platelet volume to platelet count in acute mesenteric ischemia

Introduction: Acute mesenteric ischemia (AMI) is a condition in which there is a sudden cessation of blood supply to a particular intestinal segment and consequent cellular damage. Although it has a low incidence of approximately 0.09-0.2% of all emergency surgery admissions, AMI is a severe condition that can cause high early mortality. A direct relationship between an increased mean platelet volume (MPV) and acute thrombotic events has been shown in recent years. we aimed to find out whether the diagnosis of mesenteric ischemia and the amount of bowel segment affected by ischemia will guide clinicians preoperatively with these markers&#x0D; Material and Method: A total of 57 cases with bowel resection due to mesenteric ischemia were included in the study. The gender, age, serum platelet (PLT), MPV, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), Albumin, CRP, neutrophil-lymphocyte ratio (NLR), MPV/Platelet Count, and CRP-albumin ratio (CAR) levels at the time of admission, operation time, length of resected bowel segment, length of hospital stay, presence of necrosis and perforation from pathology reports, and length of bowel segment leading to necrosis were scanned.&#x0D; Results: A moderate (moderate) negative correlation was found between the length of resected bowel segment and PLT (P

COVID-19, Vaccines, and Thrombotic Events: A Narrative Review.

The coronavirus disease 2019 (COVID-19), a deadly pandemic that has affected millions of people worldwide, is associated with cardiovascular complications, including venous and arterial thromboembolic events. Viral spike proteins, in fact, may promote the release of prothrombotic and inflammatory mediators. Vaccines, coding for the spike protein, are the primary means for preventing COVID-19. However, some unexpected thrombotic events at unusual sites, most frequently located in the cerebral venous sinus but also splanchnic, with associated thrombocytopenia, have emerged in subjects who received adenovirus-based vaccines, especially in fertile women. This clinical entity was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia, probably caused by cross-reacting anti-platelet factor-4 antibodies activating platelets. For this reason, the regulatory agencies of various countries restricted the use of adenovirus-based vaccines to some age groups. The prevailing opinion of most experts, however, is that the risk of developing COVID-19, including thrombotic complications, clearly outweighs this potential risk. This point-of-view aims at providing a narrative review of epidemiological issues, clinical data, and pathogenetic hypotheses of thrombosis linked to both COVID-19 and its vaccines, helping medical practitioners to offer up-to-date and evidence-based counseling to their often-alarmed patients with acute or chronic cardiovascular thrombotic events.

Evaluation of efficacy and safety of rivaroxaban combined with aspirin in patients with chronic coronary artery disease: A protocol for systematic review and meta-analysis.

Background:Coronary artery disease (CAD) is among the main causes of morbidities and mortalities globally. It is also considered to be an outcome of acute thrombotic events which entail activating platelets as well as coagulation proteins. In particular, rivaroxaban along with aspirin have been considered to reduce thrombotic events. However, they are yet to be evaluated by combining with or putting them against each other in patients experiencing CAD. This study intends to carry out an evaluation of whether combining rivaroxaben with aspirin will be effective and safe in treating patients experiencing chronic CAD.Methods and analysis:We intend to search information from the following databases: MEDLINE, EMBASE, Web of Science, Cochrane library, WanFang, and China National Knowledge Infrastructure. In the search, we intend to regard randomized control trials written in either English or Chinese and only those published until December 2021, as well as only those that have assessed the effectiveness and safety of combining rivaroxaban and aspirin in treating patients suffering from chronic CAD. We intend to accompany the study identification with searching or relevant reference lists as well as citations. We will also contact respective authors to provide additional information or data were needful. From the search, we will collate all citations identified and remove all duplicates. Similarly, 2 independent authors will screen all the titles and abstracts and assess them against the inclusion criteria for the study. Only selected studies will be included for critical appraisal, extraction of data, and synthesis. We will then conduct statistical analyses by utilizing a random-effect model.Ethics and dissemination:This study does not require ethical approval as the findings will be published in a peer-review journal.Registration number:10.17605/OSF.IO/WBGE4

Venous Thromboembolism and Cancer: A Comprehensive Review from Pathophysiology to Novel Treatment.

Acute thrombotic events can unveil occult cancer, as they are its first manifestation in about 20 to 30% of all cases. Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. The main pathway involved in these reactions involves the activation of tumor-associated procoagulant factors, which eventually results in clot formation. The clinical manifestation of cancer-related thrombotic events mainly involves the venous side, and manifests in a broad spectrum of conditions, including unusual sites of venous thrombosis. The selection of patients who have a balanced risk–benefit profile for management of anticoagulation is complex, given individual patient goals and preferences, different prognosis of specific cancers, common comorbidities, potential drug–drug interactions, underweight states, and the competing risks of morbidity and mortality. Anticoagulant treatment in cancer settings is broadly debated, considering the potential application of direct oral anticoagulants in both thromboprophylaxis and secondary prevention, having demonstrated its efficacy and safety compared to conventional treatment. This review aims to provide a brief overview of the pathophysiology and management of cancer-related thrombosis, summarizing the results obtained in recent clinical trials.

Follow-up after acute thrombotic events following COVID-19 infection

Objective: COVID-19 infection results in a hypercoagulable state predisposing patients to thrombotic events. We report the 3- and 6-month follow-up of 27 patients who experienced acute arterial thrombotic events in the setting of COVID-19 infection.

Pre-administration of a carboxypeptidase inhibitor enhances tPA-induced thrombolysis in mouse microthrombi: Evidence from intravital imaging analysis

IntroductionThrombolysis using recombinant tissue-type plasminogen activator (rt-PA) is the pharmacological treatment of choice in acute thrombotic events. However, a narrow therapeutic window and bleeding complications limit its use. We describe the role of carboxypeptidase inhibitor from potato tuber (PTCI), an inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa), on Glu-plasminogen accumulation and microthrombus dynamics in vivo and demonstrate its influence on rt-PA-mediated thrombolysis. Materials and methodsIn conjunction with real-time intravital two-photon excitation fluorescence microscopy, we produced and imaged laser-induced microthrombi in the mesenteric venules of Green Fluorescent Protein (GFP)-expressing mice. We examined microthrombus dynamics and thrombolysis patterns in vivo by measuring the changes in the fluorescence intensity of labeled Glu-plasminogen following administration of epsilon aminocaproic acid (EACA), PTCI, and rt-PA. ResultsPTCI enhanced Glu-plasminogen accumulation at the core of the thrombus by inhibiting TAFIa, while EACA inhibited this process. Exogenous rt-PA effectively triggered Glu-plasminogen activation within the thrombus and promoted thrombolysis. Administration of PTCI and rt-PA together showed no significant benefit on thrombolysis compared to rt-PA administration alone. However, early-phase systemic administration of PTCI before thrombolytic therapy by rt-PA expedited clot lysis as evidenced by significantly faster time to reach peak Glu-plasminogen fluorescence intensity and shorter time to achieve near-complete clot lysis (P = 0.014 and P = 0.003, respectively). ConclusionsPTCI potentiates rt-PA-mediated thrombolysis when administered early in acute thrombotic events. Further studies are warranted to explore the potential of TAFI inhibitors as adjunct agents in thrombolysis or thromboprophylaxis.

697 Binding of gamma-glutamyl transferase to toll-like receptor-4 allows tissue factor activation in monocytes

Abstract Aims Gamma-glutamyl transferase (GGT) is well known to play a key role in the antioxidant processes, however, it also exerts pro-oxidant effects by activating NFkB, a redox-sensitive transcription factor key in the induction of tissue factor (TF) gene expression, the principal initiator of the clotting cascade. GGT may potentially modulate TF expression, an assumption verified by previous studies carried out in human peripheral blood mononuclear cell (PBMC). Quite importantly, TF expression in response to GGT stimulation was independent of its enzymatic properties since those experiments were conducted by using human recombinant (hr)GGT, a wheat germ-derived protein enzymatically inert because of missing post-translational glycosylation site. Thus, GGT may act through a cytokine-like mechanism although the precise determinants of its action and the receptor involved were not defined by those experiments. To assess whether GGT-induced TF stimulation is a consequence of binding to toll-like receptor (TLR)-4 and activation of NFkB, as suggested by results recently obtained in different experimental contexts. Methods PBMCs obtained from healthy donors through a discontinuous Ficoll/Hystopaque density gradient and THP-1 cells, a human monocytic cell line derived from an acute monocytic leukaemia patient, were incubated with hrGGT (0.5 ng/μL for PBMCs and 1 ng/µL for THP-1). LPS-Rs (0.5 ng/µL for PBMCs and 1 ng/µL for THP-1), CLI-095 (3 × 10−6M) and BAY-11-7082 (10−5 M) were used to block TLR-4 receptors, TLR4 signalling and NFkB respectively. TF protein concentration was determined by western blot analysis. TF pro-coagulant activity (PCA) was assessed through the use of Start Max coagulometer and results were expressed in pg/mL after calibration with a standard curve. HEK-Blue hTLR4-positive and HEK-Blue hTLR4-negative cells are used to evaluate the engagement of TLR4 by hrGGT. Results hrGGT increased TF expression in both PBMCs (PCA from 110 ± 70 to 510 ± 43, n = 7, P &amp;lt; 0.01) and THP-1 cells (PCA from 170 ± 64 to 460 ± 80, n = 15, P &amp;lt; 0.001), result confirmed by western blot. In PBMCs GGT-induced TF stimulation was antagonized by LPS-Rs (PCA: −72 ± 17% n = 4, P &amp;lt; 0.01) a TLR-4 antagonist, CLI-095 (PCA: −74 ± 34%, n = 7, P &amp;lt; 0.001) a TLR-4 intracellular antagonist and BAY-11-7082 (PCA: −71 ± 32%, n = 7, P &amp;lt; 0.001), a NF-kB inhibitor. Similar results were obtained in THP-1 cells (LPS-Rs: −76 ± 15%, n = 6, P &amp;lt; 0.01; CLI-095: −100 ± 6,6 %, n = 6, P &amp;lt; 0.01; BAY-11-7082: −100 ± 2,1%, n = 6, P &amp;lt; 0.01). hrGGT activates NFkB in hTLR4-positive HEK cell lines while does not induces effect in TLR4-negative HEK cell lines. Conclusions These data confirm the cytokine-like activity of GGT and its procoagulant effect in PBMCs and THP-1 cells. Furthermore, it is highlighted for the first time the possible role of TLR-4 as the receptor of GGT and NFkB as the involved signal transduction pathway. The GGT-TLR-4 link may provide an explanation to the consistent association between circulating GGT levels and increased risk of acute thrombotic events as well as to the involvement of GGT in the morbid evolution of the silent atherosclerotic plaque in which GGT colocalizes with monocytes and foam cells, the prime sources of TF within the plaque.