Risk Of Thromboembolic Disease Research Articles

Abstract 4134384: Sotagliflozin, a Dual Inhibitor of Sodium-Glucose Transporters 1 and 2, Elicits Cardioprotective Effects Through Attenuation of Platelet Activation and Thrombosis

Sodium-glucose cotransporter (SGLT) inhibitors are used in the treatment of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). In the SCORED trial, sotagliflozin (SOTA), a dual SGLT1/2 inhibitor, demonstrated significant reductions in both myocardial infarction (MI) and stroke in patients with T2DM and CKD. These results suggest a cardiovascular (CV) benefit of SOTA in patients with T2DM and CKD who are at increased risk of thromboembolic disease. To investigate the underlying mechanism of CV protection, we evaluated the effects of SOTA on platelet activation and thrombus formation, in both in vivo and ex vivo models, to understand its effects on MI and stroke. Washed human platelets treated with SOTA were stimulated with various agonists and platelet activation was assessed via lumi-aggregometry and flow cytometry. In whole blood, SOTA was evaluated for its potential to reduce platelet adhesion and thrombus formation in the perfusion flow chamber and Total Thrombus formation Analysis System (TTAS) assays. In vivo , mice dosed with SOTA were assessed for thrombus formation at the site of injury in real-time in the cremaster arteriole injury model. To determine the effect of SOTA on hemostasis, we assessed coagulation parameters ex vivo in human whole blood using thromboelastography. Finally, bleeding time was measured in vivo in mice dosed with SOTA using the tail bleeding assay. In washed platelets, SOTA inhibits platelet activation and aggregation in a dose-dependent manner. Similarly, a dose-dependent decrease in platelet adhesion and thrombus formation was observed in whole blood assays. In vivo , platelet accumulation and fibrin formation were decreased in mice dosed with SOTA, however no effect is observed in coagulation parameters or bleeding time. SOTA inhibits platelet activation and thrombus formation with no impact on coagulation parameters or bleeding potential. These findings highlight a potential mechanism through which SOTA reduces the risk of stroke and MI in patients with T2DM and CKD, underscoring the importance of further investigation into the role of SOTA in CV protection, particularly in patients suffering from both T2DM and CKD at high risk of thromboembolic events.

Pulmonary Embolism in Critically Ill Patients-Prevention, Diagnosis, and Management.

Critically ill patients in the intensive care unit (ICU) are often immobilized and on mechanical ventilation, placing them at increased risk for thromboembolic diseases, particularly deep vein thrombosis (DVT) and, to a lesser extent, pulmonary embolism (PE). While these conditions are frequently encountered in the emergency department, managing them in the ICU presents unique challenges. Although existing guidelines are comprehensive and effective, they are primarily designed for patients presenting with PE in the emergency department and do not fully address the complexities of managing critically ill patients in the ICU. This review aims to summarize the available data on these challenging cases, offering a practical approach to the prevention, diagnosis, and treatment of PE, particularly when it is acquired in the ICU.

Venous Anomalies in Overgrowth Syndromes

Overgrowth syndromes, particularly within the PIK3CA-related overgrowth syndrome (PROS)spectrum, are commonly associated with venous anomalies. The anomalies include spongiform venous malformations and persistent embryonic veins, such as the lateral marginal vein (of Servelle). The anomalous veins pose a significant risk of thromboembolic disease and should be occluded, preferably earlier in life. A thorough understanding of the conditions, anatomy, and interdisciplinary treatment of these complex anomalies is essential for optimal management. This review explores the clinical and imaging diagnosis of overgrowth syndromes and techniques for assessing and treating associated venous anomalies, particularly the endovenous closure of anomalous veins

Usage of the levonorgestrel releasing intrauterine system in perimenopause.

Levonorgestrel releasing intrauterine system have excellent contraceptive efficacy with simultaneous lowering of menstruation's blood loss. It could be used for therapy of endometrial hyperplasia in perimenopause. In position of gestagen part of the hormone replacement therapy it has high control of endometrial proliferation. It is conjoined with the zero increasing of risk of thromboembolic disease in combination with transdermal oestrogen's application.

Thrombotic and neuropsychiatric sequelae in post-coronavirus disease 2019 end-stage renal disease patients on maintenance hemodialysis

Background End-stage renal disease (ESRD) patients on maintenance hemodialysis (MHD) are highly vulnerable to severe manifestations of coronavirus disease 2019 (COVID-19) as increased risk of thromboembolic disease and worsened neuropsychiatric status. Aim To assess the long-term thrombotic and neuropsychiatric sequelae of severe acute respiratory syndrome corona virus 2 in post-COVID-19 ESRD patients on MHD. Patients and methods We followed for 12 months, 35 clinically stable HD patients on MHD who were confirmed or highly suspected for COVID-19 by positive severe acute respiratory syndrome corona virus 2 RT-PCR and/or high probability on high-resolution computed tomography chest imaging. We recorded demographics, HD and COVID-19 related data, thromboembolic history, and psychiatric history. We recorded baseline and follow-up complete blood count with differential counts, D-dimer, prothrombin time, international normalized ratio, and high-resolution computed tomography chest findings. We assessed post-COVID-19 neuropsychiatric sequelae using the Arabic versions of Hamilton’s depression rating scale and Taylor’s manifest anxiety scale. Results Total leukocytic count, lymphocytes, and platelets were significantly lower during infection than preinfection, 6 months, and 1-year postinfection (P<0.001, P=0.003, P=0.014, respectively). Six months after infection, d-dimer levels were higher than normal values. The incidence of vascular access thrombosis was 25.7%. The scores of Hamilton’s depression rating scale and Taylor’s manifest anxiety scale were high [25 (interquartile range; 17–28) and 26 (interquartile range; 19–33)], respectively, and the prevalence of depression and anxiety symptoms were 94.3 and 85.7%, respectively. Conclusions During infection, ESRD patients showed significantly lower total leukocytic count, lymphocytes, and platelets than preinfection, 6 months, and 1-year postinfection. They had high levels of d-dimer 6 months postinfection and a high risk for vascular access thrombosis. Their psychological wellbeing was markedly impaired by the pandemic resulting in depression and anxiety.

Injection sclerotherapy for the treatment of haemorrhoids in anticoagulated patients.

Symptomatic haemorrhoids (SH) are a common condition; however, conventional outpatient treatment, including rubber band ligation, is contraindicated in patients receiving concurrent anticoagulation. Injection sclerotherapy (IST) has been proposed as a treatment option for these patients. A retrospective review of case notes was performed in a colorectal surgery department that sits alongside a tertiary cardiothoracic surgical unit. Patients treated with an IST for SH between 1 April 2014 and 30 November 2021 were identified. Anticoagulation was not stopped in these patients as they were at high risk of developing thromboembolism, except in two patients who required alternative procedures. The primary outcome was symptom resolution, defined as no patient reporting bleeding for at least six months. The secondary outcomes were patient-reported complications, number of IST procedures and number of other procedures performed to achieve symptom resolution. A total of 20 patients with a median age of 64 years (range 35-86, 14 male) who underwent 32 IST treatments were identified. Symptom resolution was achieved in 18 (90%) patients using IST while continuing anticoagulation treatment, with two (10%) patients requiring alternative interventions. Ten patients (50%) required only one IST procedure, and three patients (15%) required two procedures. The remaining five (25%) patients required three or four interventions. The median time between IST treatments was 32 weeks (range 8-133). No complications were reported. Our study demonstrates that IST can be considered as a potential treatment option for patients with SH who are at a high risk of thromboembolic disease requiring anticoagulation.

Increased contact activated endogenous thrombin potential in pregnant women with preeclampsia.

Preeclampsia is a worldwide contributor to maternal and fetal morbidity and mortality. Women with preeclampsia are in a hyper-coagulable state with increased risk of thromboembolic disease later in life compared with normal pregnant women. The contact system (CAS) in plasma can mediate thrombin generation and is an important contributor to thrombus growth, but the activation of CAS during pregnancy complicated by preeclampsia is not yet elucidated, and CAS may play a role in the pathophysiology of preeclampsia. Therefore, the aim of the study is to address thrombin generation, and in particular, the capacity of the CAS-mediated pathway in patients with preeclampsia compared with pregnant controls. One hundred and seventeen women with preeclampsia and matched controls were included. The project was registered at www.clinicaltrials.gov as NCT04825145. CAS and tissue factor induced thrombin generation, proteins C and S, antithrombin, and histidine-rich glycoprotein (HRG) were assessed. Women with preeclampsia had significantly increased CAS and tissue factor-induced endogenous thrombin potential (ETP), and HRG compared with controls, P = 0.022, P = 0.024, and P = 0.02, respectively. The concentrations of protein C and antithrombin were significantly reduced in the preeclampsia group, P = 0.024 and P < 0.0001, respectively. No significant difference in the concentration of protein S was detected, P = 0.06. This study demonstrates a significant increased CAS-induced ETP and an overall decrease of important regulators of coagulation in women with preeclampsia compared with controls. These aspects can contribute to the hyper-coagulable state characterizing preeclampsia.

A Case Report on the Unique Challenges of COVID-19 Infection During Perioperative Anesthesia Care for a Laboring COVID-19-Infected Mother in a Low-Resource Area

BACKGROUND:Recently, the rate of cesarean sections has increased, addressing the concern of anesthesia for cesarean sections in a similar manner. Physiological changes during pregnancy, such as increased cardiac output, heart rate, and oxygen consumption, decreased lung compliance and capacity, immune modulation (an altered response of the cell-mediated immunity), and increased risk of thromboembolic disease reduce maternal compensation during stress and certain pathological conditions like infections. Importantly, the provision of anesthesia for a pregnant mother is perceived as a challenging situation because of the attendant physiological, anatomical, and pharmacological changes in pregnancy. This culminates in the modification and dosage adjustment for certain medications, especially sedative-hypnotics and delivery, as well as the management of anesthetic techniques, to optimize and ensure maternal organ function and fetal well-being.Certain perioperative factors, such as COVID-19 infection, comorbid disease, and obstetric complications, increase the risk of maternal morbidity and mortality with a subsequent fetal compromise during the perioperative state, besides the aforementioned anesthetic challenges. Moreover, COVID-19 infection increases the perils of complicating pregnancy and pregnancy outcomes, including maternal artificial ventilation and intensive care admission, preterm labor, fetal distress, neonatal intensive care admission, and fetal and maternal deaths.CONCLUSION:Preventive strategies toward the spread of the COVID-19 infection, vaccines, and the proper use of personnel protective equipment by healthcare providers reduce the spread and severity of the COVID-19 infection and improve obstetric and pregnancy outcomes.

The Comparison of Soluble P-selectin, Anti-platelet Factor 4, and Platelet Maximum Aggregation Levels among Coronavirus Disease 2019 Patients

Abstract INTRODUCTION: The coronavirus disease 2019 (COVID-19) continues to have an enormous and extensive effect on global health, causing widespread devastation. Patients who have recovered from COVID-19 have an increased risk of thromboembolic disease. We suggest that soluble P-selectin and anti-platelet factor 4 (anti-PF4) plays a significant role in platelet activation, ultimately resulting in thrombosis. The purpose of this study is to compare the role of soluble P-selectin, anti-PF4, and platelet maximal aggregation levels in COVID-19 patients. MATERIALS AND METHODS: A cross-sectional study was conducted among COVID-19 patients who were admitted to the hospital between October 2021 and January 2022. RESULTS: From 160 individuals, we found that a number of individuals with older age (P = 0.014) and lower hemoglobin levels (P = 0.042) were significantly higher in the severe COVID-19 group compared to the nonsevere COVID-19 group. Remarkably, soluble P-selectin levels in mild-to-moderate COVID-19 were found to be significantly higher than the severe group, with statistical significance (P = 0.02). However, there was no significant difference in anti-PF4 levels between severe and nonsevere COVID-19 groups. Furthermore, platelet maximum aggregation was also significantly higher in the severe COVID-19 group than in the mild-to-moderate COVID-19 group by using 2.5 μM (P = 0.024), 5 μM (P = 0.026), and 10 mM adenosine-diphosphate (P = 0.02). CONCLUSION: Soluble P-selectin, an indicator of platelet activation, was shown to be significantly higher in mild-to-moderate COVID-19 group than the severe COVID-19 group. The maximum aggregation of platelets was also observed to be significantly greater in the severe COVID-19 group.

The Role of Mechanical Thrombectomy for Acute Massive Pulmonary Embolism in a Patient With Unilateral Lung Transplant and Atrial Septal Defect.

The risk of thromboembolic disease is high in patients with lung transplantation and is associated with significant morbidity and mortality with single healthy transplanted lung. We present a case involving successful endovascular management of life-threatening acute massive pulmonary embolism (PE) in a patient with single lung transplant and atrial septal defect (ASD). A 65-year-old man with a history of interstitial lung disease status post single left orthotopic lung transplant in 2012 presented with acute massive PE and clot burden in the pulmonary arteries of the transplanted left lung. Severe right heart dysfunction, hemodynamic instability, and requirement for vasopressors persisted post systemic thrombolytic therapy. As a result, the patient underwent successful endovascular mechanical thrombectomy with immediate improvement in oxygen saturation and hemodynamic status. The procedure was performed without adverse outcomes or paradoxical embolization despite the presence of ASD. The right heart dysfunction resolved, the patient was extubated the next day, and was discharged to home 2 days post procedure. Endovascular mechanical thrombectomy was safely used to treat acute massive PE in a single transplanted lung in the presence of ASD. Endovascular mechanical thrombectomy could be safely utilized to treat patients with lung transplant and acute massive or submassive pulmonary embolism. However, safely of mechanical thrombectomy should be determined in case-based scenarios and based on time interval from transplantation to when the thrombectomy is required.

Effect of Anticoagulants in Pulmonary Thromboembolism in Post-COVID-19 Patients.

Background and objective COVID-19 may predispose to both venous and arterial thromboembolism (VTE and ATE) due to excessive inflammation, immobilization, and hypoxia. The purpose of this study is to evaluate clinical and laboratory risk factors, as well as related medications such as anticoagulants, to predict the risk of thromboembolic disease and/or death in COVID-19 patients. Methods Over a period of 14 months (from August 2020 to September 2021), a total of 145 consecutive patients with signs and symptoms suspicious of pulmonary embolism (PE) were referred for perfusion single-photon emission computed tomography/computed tomography (Q SPECT/CT). All patients had a history of SARS‑CoV‑2 infection, diagnosed with a positive real-time polymerase chain reaction (RT-PCR) test. Results Among the 145 patients included in the study, the risk of PE was found to be greater in elderly patients (odds ratio [OR] [95% CI]: 1.05 [1.02‑1.07]; p<0.001) and in patients with higher maximum d-dimer levels (OR [95% CI]: 1.14 [1.01‑1.3]; p=0.04). We also analyzed the utility of the maximum d-dimer level for predicting acute PE with receiver operating characteristic (ROC) curve analysis. For d‑dimer = 0.5 mg/dL, cut-off sensitivity is 91%, specificity is 23%, and for d-dimer = 1 mg/dL, cut-off sensitivity is 79%, specificity is 43% Conclusion D-dimer titers were higher in the PE group in our study. Another significant finding was that, possibly due to thromboinflammation, anticoagulants did not prevent the development of PE in COVID-19 patients.

Safety of Janus Kinase Inhibitors in Inflammatory Bowel Diseases.

In recent years, better knowledge of the pathophysiology of inflammatory bowel diseases (IBD) has led to a relevant expansion of the therapeutic arsenal for these conditions. Janus kinase (JAK) inhibitors are a family of small molecules that block one or more of the intracellular tyrosine kinases, including JAK-1, JAK-2, JAK-3 and TYK-2. Tofacitinib, a non-selective small molecule JAK inhibitor, andupadacitinib and filgotinib, which are selective JAK-1 inhibitors, have been approved by the US Food and Drug Administration (FDA) for moderate-to-severe active ulcerative colitis. Compared to biological drugs, JAK inhibitors have a short half-life, rapid onset of action, and no immunogenicity. Both clinical trials and real-world evidence support the use of JAK inhibitors in the treatment of IBD. However, these therapies have been linked with multiple adverse events (AEs) including infection, hypercholesterolemia, venous thromboembolism, major adverse cardiovascular events, and malignancy. While early studies recognized several potential AEs, post-marketing trials have shown that tofacitinib may increase the risk of thromboembolic diseases and major cardiovascular events. The latter are seen in patients aged 50 years or older with cardiovascular risk factors. Hence, thebenefits of treatment and risk stratification need to be considered when positioning tofacitinib. Novel JAK inhibitors with a more selective effect on JAK-1 have proven to be effective in both Crohn's disease and ulcerative colitis, offering a potentially safer and efficacious therapeutic option to patients, including those with previous non-response to other therapies such as biologics. Nevertheless, long-term effectiveness and safety data are required.

Thoracoscopic Left Atrial Appendage Exclusion for Atrial Fibrillation Patients Intolerant to Anticoagulation.

Outcomes associated with isolated epicardial left atrial appendage (LAA) exclusion in atrial fibrillation (AF) patients with a contraindication or intolerance to anticoagulation are not clearly defined, especially in patients with prior stroke. This study evaluated the perioperative safety, medication use, and stroke outcomes for isolated thoracoscopic LAA exclusion for stroke prevention. A single-center retrospective study was performed of adults undergoing isolated thoracoscopic LAA exclusion with an epicardial exclusion device without a concomitant surgical procedure. Descriptive statistics were performed. Twenty-five patients met the inclusion criteria. The cohort was 68% male (n = 17) with a mean age of 76.4 ± 6.5 years, a mean preoperative CHA2DS2-VASc score of 4.2 ± 1.4, and a mean preoperative HAS-BLED score of 2.68 ± 1.03. Seventeen patients (68%) had nonparoxysmal AF. There were 11 patients with intolerance of anticoagulation due to intracranial hemorrhage (44%), 6 due to gastrointestinal bleeding (24%), and 4 due to genitourinary bleeding (16%). All procedures were performed thoracoscopically with 100% technical success-the mean LAA stump length was 5.5 ± 2.3 mm on intraoperative transesophageal echocardiography. The median hospital length of stay was 2 (interquartile range [IQR] 1, 6.5) days. The median follow-up time was 430 (IQR 125, 972) days. During follow-up, 1 patient with cerebral angiopathy had temporary neurologic deficits at an outside institution, with brain imaging showing no evidence of ischemic injury. There were no other thromboembolic events over the 38.8 postoperative patient-years examined. All patients were off anticoagulation at last follow-up. This study shows the perioperative safety, technical success, freedom from anticoagulation, and stroke outcomes of isolated thoracoscopic LAA exclusion in patients with AF at high risk for thromboembolic disease.

Drugs to reduce bleeding and transfusion in major open vascular or endovascular surgery: a systematic review and network meta-analysis.

Drugs to reduce bleeding and transfusion in major open vascular or endovascular surgery: a systematic review and network meta-analysis.

Increased In Vivo Thrombin Generation in Patients with Localized Non-Small Cell Lung Cancer Unfit for Surgery.

Patients with lung cancer face a substantially increased risk of thromboembolic disease. Patients with localized non-small cell lung cancer (NSCLC) who are unfit for surgery due to age or comorbidity have additional thrombotic risk factors. Thus, we aimed to investigate markers of primary and secondary hemostasis, since this could assist in treatment decisions. We included 105 patients with localized NSCLC. Ex vivo thrombin generation was determined by calibrated automated thrombogram and in vivo thrombin generation was determined by measurement of thrombin-antithrombin complex (TAT) levels and prothrombin fragment F1 + 2 concentrations (F1 + 2). Platelet aggregation was investigated by impedance aggregometry. Healthy controls were used for comparison. TAT and F1 + 2 concentrations were significantly higher in NSCLC patients than in healthy controls (P < .001). The levels of ex vivo thrombin generation and platelet aggregation were not increased in the NSCLC patients. Patients with localized NSCLC considered unfit for surgery had significantly increased in vivo thrombin generation. This finding should be further investigated as it could be relevant for the choice of thromboprophylaxis in these patients.

OSTEOPOROSIS IN PATIENTS WITH COPD AND IMPACT ON QUALITY OF LIFE

Chronic obstructive pulmonary disease (COPD) is a progressive disease parenchyma destruction. Smoking is a major risk factor for this disease with frequent comorbidities. Osteoporosis is a common comorbidity in patients with COPD. Osteoporosis is characterized by lower bone density and changes in bone microarchitecture, leading to increased sensitivity and bone fractures occur. Fractures cause pain, further worsen already damaged pulmonary ventilation, reduced mobility and disability, and increased risk of thromboembolic disease, and even death. Osteoporosis in patients with COPD is probably evolving as the basis for both diseases there is systemic inflammation, but also because of the influence of inhaled tobacco smoke, reduced mobility of patients, vitamin D deficiency, lower body weight and older age. The use of systemic corticosteroids in the treatment of exacerbations of COPD increases the risk of developing osteoporosis. In addition, exacerbation of the intensification of inflammation, hypoxia and oxidative stress, as well as the imbalance between protease and anti-protease may contribute to increased bone resorption in patients with COPD. Osteoporosis can lead to kyphosis, which limits physical activity, leads to dyspnea, exacerbations and inadequate ventilation, which leads to a decrease in pulmonary function parameters. Osteoporosis can cause fractures that further limit movement, increasing the risk of thromboembolism and death. All of that have large impact on the quality of life COPD patients. Early prevention, timely diagnosis and treatment of osteoporosis are very important for patients with COPD. It is necessary significantly increase awareness of the connection between these two diseases.

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.

Thromboembolic events in left ventricular non-compaction: comparison between children and adults – a systematic review and meta-analysis

ObjectiveLeft ventricular non-compaction (LVNC) is morphologically characterised by excessive trabeculations and deep recesses in the ventricular wall. The risk of thromboembolic disease in the paediatric patients with LVNC has not...

Autoimmune Diseases and Rates of Thromboembolism in Pregnancy [A278

INTRODUCTION: Antiphospholipid syndrome (APLS) is associated with an increased risk of thromboembolism during pregnancy. Other autoimmune diseases are less well-studied. Given the pro-inflammatory state associated with these conditions, we sought to identify the risk of thromboembolic disease in pregnant patients with autoimmune conditions. METHODS: This is a retrospective cohort study utilizing the National Inpatient Sample (Healthcare Cost and Utilization Project) for the year 2018. Subjects were excluded if they had a history of thrombosis, inherited thrombophilia, or APLS. Patients with at least one autoimmune condition (rheumatoid arthritis, Type 1 diabetes, systemic lupus erythematosus, myositis, ulcerative colitis, Crohn's, Sjogren's, scleroderma, and Hashimoto's thyroiditis) were compared to unaffected pregnancies. The primary outcome was a composite of thrombotic events. Secondary outcomes included individual components of the composite including deep vein thrombosis, PE, arterial embolism, and cerebrovascular thrombosis. The groups were compared via Student's t-tests, Chi-square, and logistic regression analyses. RESULTS: The control cohort comprised 750,743 pregnancies. The study cohort had 8,605 patients with≥1 autoimmune condition. The patients with autoimmune conditions were more likely to be older, White, obese, chronic hypertensive, tobacco users, privately insured, and in the upper quartile of household income (all P&lt;.001). After controlling for confounders that differed between groups with P&lt;.05, presence of an autoimmune disease was independently associated with higher rates of thrombosis and embolic events, with rates of 0.6% compared to 0.2% in controls (aOR 2.40, 95%CI 1.75–3.28). CONCLUSION: Autoimmune disease is associated with an increased risk of thromboembolic disease in pregnancy.

Incidence and Prevention of Thromboembolic Complications for Sports and Arthroscopic-related Surgery: Evidence-based Recommendations.

The incidence of thromboembolic events following arthroscopic surgery is relatively rare. Despite this, these are important complications to be aware of, as arthroscopic procedures are performed in high frequency each year and can lead to a substantial burden within health care. Over the past several decades, pharmacologic antithrombotic prevention strategies following knee arthroscopy have been extensively studied; however, their efficacy remains controversial, and there is a lack of consensus regarding a standard prevention protocol, with the exception of the established benefits of early mobilization. Several surgical and medical risk factors have been established and are important to consider as they specifically relate to each individual patient's risk of thromboembolic disease. Based on the best available evidence, chemical thromboprophylaxis appears to be unnecessary among healthy patients but may be beneficial for higher risk patients, especially those with a prior history of venous thromboembolism. A standard screening tool for risk factors in arthroscopy patients may be a cost-effective and safe solution for implementing preventative efforts.