Risk Of Thrombosis In Patients Research Articles

Can Rosuvastatin Reduce the Risk of Thrombosis in Patients with Hypercholesterolemia with its Effect on Coagulation Factors and Homocysteine Levels?

Hypercholesterolemia is one of the main risk factors for vascular thrombosis in individuals. Therefore, the use of statins is very effective in reducing cholesterol and can reduce the risk of thrombosis in these patients. Rosuvastatin, a member of the statin family which, inhibits cholesterol synthesis. Very few studies have been done in relation to how rosuvastatin can affect thrombosis. So, this research has been tried whether rosuvastatin can have an effect on coagulation factors and homocysteine as risk factors for thrombosis in hypercholesterolemia? In this experimental study, 60 patients (30 men and 30 women with a mean age of 40- 70 years) diagnosed with hypercholesterolemia (cholesterol >250 mg/dl) participated in this research. 30 patients were prescribed rosuvastatin (20 mg/day), and 30 patients were simultaneously taken placebo for three months. All parameters, including FVIII, FV, Fibrinogen, D-Dimer, plasma homocysteine level and lipid profile, were measured before and after treatment. All the results were statistically compared between the two groups. In patients who took rosuvastatin, the drug was able to significantly reduce the concentrations of total cholesterol, triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) (P <0.001). Also, rosuvastatin was able to reduce the concentrations of homocysteine significantly, D-Dimer (P <0.001), coagulation factor VIII and factor V (P <0.05). In patients with hypercholesterolemia who took the placebo, did not affect the mentioned variables (P >0.05). According to the results, it seems that rosuvastatin may be able to reduce the risk of thrombosis in patients by affecting coagulation factors and homocysteine levels.

Sternocleidomastoid muscle-splitting method for high cervical carotid endarterectomy: illustrative cases.

The number of cervical carotid endarterectomies (CEAs) has decreased as carotid artery stenting (CAS) has increased. However, CEA and CAS both have advantages and disadvantages; therefore, appropriate procedures must be selected for individual patients. High-positioned carotid artery stenosis presents technical challenges for CEA and is occasionally managed by performing CAS. However, CAS is associated with a high risk of thrombosis in patients with soft plaques, suggesting a clinical need for a better procedure. Consequently, appropriate surgical treatment for patients requiring high-level CEAs is essential. In this study, a novel and straightforward method was devised. The primary concept underlying this technique is separation of the sternocleidomastoid muscle (SCM) from other anatomical structures to ensure a wider surgical field. By anatomically separating the SCM into the sternal and clavicular head groups, the objective of the wider surgical field can be met. Herein, we report technical innovations in high-positioned carotid artery stenosis and evaluate their efficacy in two patients. In conclusion, high CEA surgery using this new method is valuable and may eliminate barriers to more advanced approaches.

Маркеры эндотелиальной дисфункции у реконвалесцентов коронавирусной инфекции COVID-19

Vessel endothelial dysfunction is one of the key reasons for the development of thrombosis and unfavorable outcome in patients with COVID-19 coronavirus infection. The risk of thrombosis in patients with COVID-19 may persist during the convalescence period, after discharge from hospital. The purpose — to assess hemostatis in convalescents with moderate COVID-19. Material and methods. The study of hemostasis was conducted in 32 patients aged 40 to 79 years with coronavirus infection COVID-19 during the period of convalescence, after discharge from hospital. The control group consisted of 20 healthy people of the same age. The study included determining biomarkers of endothelial dysfunction in venous blood: P-selectin, von Willebrand factor (VWF), D-dimer and thrombomodulin. Results. It was found that in 24 of 32 patients (75%) after COVID-19 the level of D-dimer was significantly higher than in the control group. Median D-dimer was elevated even 3-4 months after discharge from hospital. P-selectin levels were elevated in 12 (37%) patients who recovered from COVID-19. The median P-selectin was higher than that of the control group 3-4 months after discharge from hospital. A decrease in thrombomodulin levels was recorded in 10 patients (31%). The parameter median was lower than that in the control group only during the first 2 months after discharge from hospital. The values of the FFB factor in patients after COVID-19 did not differ from those in the control group. Conclusion. A significant proportion of convalescents with moderate COVID-19, even 3-4 months after discharge from hospital, retain endothelial dysfunction and procoagulant potential, which causes the risk of thrombotic complications.

Risk factors of first thrombosis in obstetric antiphospholipid syndrome

ObjectiveThere is limited evidence on long-term thrombosis risk in patients with obstetric antiphospholipid syndrome (OAPS). This study aimed to investigate the clinical features and risk factors associated with the first...

Geographic differences in serious bleeding event rates and clinical profiles among patients with ESKD who receive peritoneal or hemodialysis, 2009-2022

Abstract Background Patients with end-stage kidney disease (ESKD) have higher rates of bleeding compared to the general population. Therapies to manage risk of thrombosis in patients with ESKD, like anticoagulants, can further increase this risk. Despite these risks, there are limited epidemiological data on bleeding rates in ESKD patients including how this risk varies across geographies. Our aim was to quantify serious bleeding event rates among patients with ESKD who are on dialysis across 5 global regions. Methods Data for this analysis come from 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS; 2009-2022) and 8 countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS; 2014-2022), both prospective studies among patients treated with hemodialysis (HD) and peritoneal (PD), respectively. Patient characteristics and bleeding rates across 5 regions were analyzed: Australia/New Zealand (ANZ), Europe, Gulf Coast Countries (GCC) (only HD), North America (NA), and Other Asia-Pacific (AP). Counts of first serious bleeding event (i.e., leading to death or inpatient hospitalization) were calculated as event rates per 100 person-years. Results In all, 32,396 and 6,068 patients on HD and PD, respectively were included (Table 1). Of patients receiving HD, 3% were from ANZ, 4% were from GCC, 14% were from North America, 28% were from AP, and 51% were in Europe. Of patients on PD, 8% were from ANZ, 7% were from Europe, 26% lived in NA, and 60% were in the AP region. Mean age for HD and PD patients generally ranged from 59-66 with PD patients tending to be a few years younger. GCC patients on HD had a mean age of 55. Both cohorts had similar distribution of sex and race. Anticoagulant use was lowest in AP and highest in NA; with lower use in PD compared to HD. Serious bleeding rates were highest in ANZ and lowest in AP. Bleeding rates leading to hospitalizations followed a similar trend. Gastrointestinal (GI) bleeding resulted in the highest bleeding event rates for hospitalizations across all regions but was highest in NA. Access bleeding was a more common reason for hospitalization in ANZ and Europe than other regions. The rate of fatal bleeding events was somewhat higher in Europe and AP than other regions with the most common fatal bleeding event being hemorrhagic stroke (Table 2), the highest of which was in AP. Conclusion These data highlight the large regional variations and inconsistent patterns in the clinical profiles, treatment patterns, and serious bleeding event rates among patients with ESKD receiving dialysis. Further research is needed to better understand factors that contribute to individual patients’ bleeding risk and to these geographic differences as a mechanism to improve risk management and quality care provided to these patients.Table 1.Patient CharacteristicsTable 2.Bleeding Rates

Relationship between MTHFR gene polymorphism and risk of thrombosis in postoperative patients with colorectal cancer.

An association between the methylenetetrahydrofolate reductase (MTHFR) C667T genotype and the risk of colorectal cancer, as well as a link between MTHFR gene polymorphism and thrombosis, have been revealed. However, the connection between MTHFR gene polymorphism and the risk of thrombosis in patients with colorectal cancer has remained to be fully elucidated. The present study investigated the link between MTHFR gene polymorphism and basic clinical data, postoperative D-dimer (DDi), postoperative thromboelastogram and postoperative thrombosis in 591 patients who underwent surgery for colorectal cancer. Postoperative DDi, thromboelastogram and postoperative thrombosis were not significantly different among patients with colorectal cancer and different MTHFR genotypes. While the results were 'negative', the present study may help physicians understand that it is not necessary to detect MTHFR polymorphism for therapeutic purposes. Regarding the danger of venous thrombosis, more focus should be placed on the standardized procedural enforcement system for deep vein thrombosis prevention for patients undergoing pelvic and abdominal surgery.

Risk Factors for Thrombosis in Essential Thrombocythemia: A Clinico-Pathological Study of 138 Patents in a Middle Eastern Population

Background: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by clonal proliferation of megakaryocyte lineage. Natural history of ET is characterized by cardiovascular events (thrombosis) along with bleeding, transformation to myelofibrosis (MF), and acute myeloid leukemia (AML). There is paucity of data in ET patients from the Arab World. We aimed to study the risk factors for thrombosis and clinical course of ET in a cohort of 138 patients in a Middle Eastern population. Methods: The study was approved by the institutional review board. All patients aged 16 or over, diagnosed with ET and followed at our center from January 2003 till June 2022, were included. Diagnosis was based on 2017 World Health Organization Classification diagnostic criteria. We gathered data on baseline clinical and laboratory characteristics from the electronic medical records and patients' files. Hematologic parameters (platelet counts, leukocyte counts, hemoglobin, and mean platelet volume [MPV]) at the time of diagnosis were retrieved and information on cardiovascular events and complications (arterial and venous thrombotic events) along with progression to myelofibrosis, acute myeloid leukemia, need for cytoreductive therapy, and control of platelet count were recorded. Multivariate regression model was used to determine the independent significant factor(s) for thromboembolism with corresponding odds ratio and 95% confidence intervals. A P-value of ≤0.05 was considered significant. Results: A total of 138 patients were included in the study. Median age of the cohort was 47 (range, 16-84) years at the time of diagnosis with 73 (52.9%) females. JAK2 V617F mutation was present in 53 (38.4%) patients, CALR in 21 (15.2%), MPL in 43 (31.2%), and 21 (15.2%) patients were triple negative. All the patients with MPL mutation had Pro106Leu mutation. After a median follow up of 5 (range 1-26) years, 31 (22.5%) patients had vascular events, 16 (51.5%) had arterial events, 13 (42%) had venous thrombosis, 4 had both arterial &amp; venous events, while 2 patients had transient ischemic attacks. Nine (6.5%) patients progressed to MF, and 5 (3.6%) to AML. Ten (7.25%) patients died, 4 due to MF or AML related and 6 due to other causes. High IPSET score was strongly associated with thrombosis (P ˂0.001). High MPV and uncontrolled (high) platelet count were associated with the risk of thrombosis in univariate analysis (P 0.006 and &amp;lt;0.001, respectively) and there was a trend towards increased risk of thrombosis in patients with high MPV and uncontrolled platelet count (P 0.061 and 0.09, respectively) in multivariate analysis. Conclusions: Our ET patient population had high prevalence of MPL (Pro106Leu) mutation which may be germ line in nature as previously reported, and correspondingly lowered the prevalence of JAK2V617F and CALR mutations in our cohort. Thrombosis developed in 26.8% patients. In multivariate analysis, a high IPSET score was strongly associated with thrombosis. There was a trend towards increased risk of thrombosis with high MPV and uncontrolled (high) platelet count. This study may help better understand the biology of ET in this population.

Increased Risk of Thrombosis in Patients with Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome (PCOS) is the most common endocrine-metabolic disorder in reproductive age women, with an estimated prevalence of 6-12% of assigned female at birth women in the US. We identified a pattern in our coagulation diagnostic management team, wherein women with PCOS had increased rates of and repeated histories of thrombotic events, such as strokes, heart attacks, pulmonary embolisms, and deep vein thromboses. However, clinical coagulation assays on these PCOS patients with repeated thrombotic events were all within the normal reference range. Our goal was to investigate the validity of this pattern and its occurrence in both local and national populations. This was accomplished by 1) Determining the incidence rate of thrombosis in PCOS and 2) Analyzing clinical presentations of thrombosis in PCOS. Methods/Study populations : Analyses on the rate of thrombotic events in PCOS patients locally at UTMB and in the US were performed on the TriNetX health research network. Using the incidence and prevalence and compared outcomes analytic functions on TriNetX, we determined the rate of thrombosis from 2013-2018 and explored patient characteristics. We further analyzed thrombosis in PCOS with the Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) method. Through the compare outcomes analysis on the TriNetX platform, we looked at PCOS and control patients who experienced thrombotic events between 2013-2018 and analyzed clinical presentations that occurred in the 90 days prior to the index event. Patient queries included the diagnostic code for PCOS, ICD10 E28.2, women age 15-75, who had a clinical encounter since 2013. Exclusion criteria included inherited thrombotic disorders, smoking history, and human immunodeficiency virus. Events of interest included myocardial infarctions, cerebral infarctions, pulmonary embolisms, arterial embolisms and thrombosis, and portal vein thromboses. Statistical analysis: For evaluating statistical significance of the rate of thrombosis, we performed a compare outcome analysis on the UTMB network, with propensity score matching for current age. A Kaplan-Meier Analysis and a student's t-test were performed on the number of instances/events, and statistical significance was defined as a p-value &amp;lt;0.0001. Results:Between 2013-2018, the incidence rate of thrombosis in PCOS patients was 4.35% with 5.36% prevalence, this was statistically significantly higher than the control cohort at 2.66% incidence and 3.5% prevalence. The incidence rate of thrombosis in PCOS increased dramatically in post-menopausal women. Of the 60 outcomes investigated, 24 were determined to be statistically significant between control and PCOS, 22 symptoms and 2 procedures. Discussion: This is the first study to analyze the rate of thrombotic events in PCOS. We identified significant presentations and gaps that could assist in the early detection of thrombotic events in PCOS. However, the mechanisms of thrombosis in PCOS are unknown and are poorly detected with current clinical assays. Future studies will examine clinical assays in the detection of thrombosis in PCOS and investigate thrombotic mechanisms in PCOS.

Using Machine Learning to Predict Near-Term Thrombosis Risk in Patients with Polycythemia Vera

Introduction: Thrombosis (arterial and venous) remains the leading cause of morbidity/mortality for patients (pts) with polycythemia vera (PV) [1-2]. With appropriate therapy, thrombosis risk can be reduced to 1-5% per year (yr) [3]. Yet some seemingly well-controlled pts still suffer thrombotic events. This rate means that a well-powered clinical trial testing anti-thrombotic strategies in PV to improve thrombosis-free survival is prohibited by the large number of pts and study duration required. For example, the high-end annual incidence of thrombosis in ELN high-risk pts is &amp;lt;5%/yr, so a 2yr study hoping to demonstrate a 50% thrombosis reduction (α=5%, 1-ß=80%) requires 1104 pts. This study would be vastly more efficient if we could enroll only pts with high near-term thrombotic risk but we cannot accurately identify these pts. To address this, we developed a machine learning (ML) approach to dynamically predict this risk. Methods: After obtaining institutional approval, 526 pts with manually verified PV diagnoses were identified by querying electronic health records and our research database repository. The dataset (4M data elements,14K hematology clinic visits) includes lab measures, molecular/pathology studies, medications, and pt history. Data completeness varied with &amp;gt;90% availability in 200+ features. To assess the error introduced by imputation, we computed the Euclidean distance/Jaccard index between masked pre-imputed data and imputed data over 8K iterations. We found that features with &amp;lt;50% missingness could be imputed without dataset corruption. ML classification models (random forest (RF), boosted models, and support vector machines) were evaluated using AutoGluon. RF emerged as the top performer. Feature engineering, guided by Gini feature importance and clinical feedback, identified 21 training features. A parallelized pipeline optimized 1.6M model combinations (# of trees, node splitting features, max depth, thresholding) via grid search. Several optimization strategies were assessed. Of 470 pts with clinic visits through Mar 31, 2020, 75% were used for model training (Training Cohort) and 25% for model evaluation (Testing Cohort). Cohort details were previously reported [4]. A prospective Validation Cohort included clinic visits after Apr 1, 2020 and was unseen by trained models. A risk calculator designed in RShiny applied models corresponding to user-entered clinical data and computed 1yr thrombosis risk. User-entered data are not stored to protect data privacy. Results: Training/Testing pts had median age of 54, and 64 (14%) had a prior thrombosis at dx (8% venous, 7% arterial). Over a median followup of 10 yrs, 159 thromboses occurred in 115 pts (88 venous, 71 arterial). Annual incidence rates (IR) of thrombosis were higher shortly after dx (IR: 4% vs 1%, 2yr cutoff) and following a thrombotic event (IR: 10% vs 2%, 2yr cutoff). The full model performed very well (F1=0.91, AUC=0.84) when compared with ELN (F1=0.1, AUC=0.39) (Figure 1). High-performing simplified models (&amp;gt;90% testing/validation sensitivity) were applied to the Validation Cohort. The full 21-feature model and high-performing models (Figure 2) showed clear separation for 1yr thrombosis risk prediction. Features of importance included blood counts, body mass index (BMI), and time since dx were frequently represented in these models. Discussion: Over 1M models were trained on high-volume clinical data to predict near-term thrombosis risk in PV pts, considering intrinsic factors (age, blood type), disease events (time since dx/thrombosis), and short-term changes (BMI) to tailor risk mitigation strategies. Prospective validation demonstrates model generalizability. External validation using REVEAL study [1] and the Danish Registry data is ongoing. Our tool's ability to identify high-risk pt populations can be applied as an inclusion criterion for prospective clinical trials, reducing the time and pt numbers needed for a well-powered study. Whereas using ELN-defined high risk would require 1K pts to demonstrate a 50% reduction in thrombosis rates, our prospective ML model-defined high near-term risk would only require ~80 pts, making such a study very feasible.

In-Hospital and readmission outcomes of patients with myeloproliferative neoplasms and atrial fibrillation: insights from the National Readmissions Database.

Patients with myeloproliferative neoplasms (MPNs) and atrial fibrillation (AF) are at increased risk of thrombosis and bleeding. However, the risk of thrombosis and bleeding in patients with AF and MPN compared with the general population with AF is unclear. Additionally, traditional risk scores (CHA2DS2-VASC and HAS-BLED) for risk/benefit estimation of thromboprophylaxis in AF do not account for MPN status. Therefore, we aimed to investigate bleeding and thrombosis risk in patients with MPN hospitalized for AF. We utilized the National Readmission Database (NRD) to identify patients with AF with and without MPN. Primary bleeding and thrombosis outcomes were in-hospital or 30-day readmission for bleeding or thrombosis, respectively. We propensity score (PS) matched patients with and without MPN. Risk of primary outcomes in MPN was assessed in PS matched cohort using logistic regression. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of primary thrombosis and bleeding outcomes, respectively. 24,185 patients without MPN were matched with 1,617 patients with MPN and variables were balanced between groups. Patients with MPN were at increased risk of meeting the thrombosis (OR 1.98, 95% CI 1.23-3.21) but not bleeding (OR 0.87, 95% CI 0.63-1.19) primary outcomes. In MPN, CHA2DS2-VASC predicted thrombosis (C-statistic 0.66, 95% CI 0.54-0.78) but HAS-BLED was a poor predictor of bleeding (C-statistic 0.55, 95% CI 0.46-0.64). In patients with AF, MPN was associated with increased risk of bleeding and thrombosis. HAS-BLED scores did not accurately predict bleeding in MPN. Further investigation is needed to refine risk scores in MPN.

A prediction nomogram for deep venous thrombosis risk in patients undergoing primary total hip and knee arthroplasty: a retrospective study

IntroductionDeep venous thrombosis (DVT) prediction after total hip and knee arthroplasty remains challenging. Early diagnosis and treatment of DVT are crucial. This research aimed to develop a nomogram for early DVT prediction.MethodsA total of 317 patients undergoing primary total hip and knee arthroplasty in Sun Yat-sen Memorial Hospital were enrolled between May 2020 and September 2022. Data from May 2020 to February 2022 were used as the development datasets to build the nomogram model (n = 238). Using multivariate logistic regression, independent variables and a nomogram for predicting the occurrence of DVT were identified. Datasets used to validate the model for internal validation ranged from March 2022 to September 2022 (n = 79). The nomogram’s capacity for prediction was also compared with the Caprini score.ResultsFor both the development and validation datasets, DVT was found in a total of 38 (15.97%) and 9 patients (11.39%) on post-operative day 7 (pod7), respectively. 59.6% patients were symptomatic DVT (leg swelling). The multivariate analysis revealed that surgical site (Knee vs. Hip), leg swelling and thrombin-antithrombin complex (TAT) were associated with DVT. The previously indicated variables were used to build the nomogram, and for the development and validation datasets, respectively. In development and validation datasets, the area under the receiver operating characteristic curve was 0.836 and 0.957, respectively. In both datasets, the predictive value of the Nomogram is greater than the Caprini score.ConclusionsA proposed nomogram incorporating surgical site (Knee vs. Hip), leg swelling, and thrombin antithrombin complex (TAT) may facilitate the identification of patients who are more prone to develop DVT on pod7.

PB0777 The Risk of Thrombosis in Patients with Acute Lymphoblastic Leukemia May Be Explained by the Impact of Peripheral Blasts on Endothelial Cells: An In-Vitro Study

PB0777 The Risk of Thrombosis in Patients with Acute Lymphoblastic Leukemia May Be Explained by the Impact of Peripheral Blasts on Endothelial Cells: An In-Vitro Study

Reduced ADAMTS13 activity and high D-dimer levels are associated with thrombosis in patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have an increased risk of vascular thrombosis compared to the general population. Therefore, biomarkers for predicting the risk of thrombosis in patients with SLE are needed. In the present study, a total of 66 patients with SLE (22 with and 44 without a history of thrombosis) were enrolled. The cases with thrombosis and the controls without thrombosis were matched for age (± 5 years) and sex. We assessed ADAMTS13 activity, D-dimer levels, and antiphospholipid antibodies. Clinical manifestations, SLE disease activity, classical risk factors, and medical history were collected. ADAMTS13 activity was significantly reduced, and D-dimer levels were significantly increased in patients with SLE with a history of thrombosis compared with those in patients without thrombosis. Receiver operating characteristic curve analysis revealed a good correlation between reduced ADAMTS13 activity and a history of thrombosis. Reduced ADAMTS13 activity was correlated with increased D-dimer levels only in the thrombotic group. Reduced ADAMTS13 activity and high D-dimer levels are associated with thrombosis and may serve as prognostic markers for thrombosis in patients with SLE.

Role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria

Objective: This study aimed to investigate the role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria (PNH) patients. Methods: A retrospective analysis was conducted on the clinical data and gene sequencing results of 45 patients with classic PNH admitted to the Department of Hematology, Tianjin Medical University General Hospital, from June 2018 to February 2022. MUC4 gene mutations in patients with classic PNH were summarized, and the risk factors for thrombotic events in these patients were analyzed. Additionally, the effects of MUC4 gene mutations on the cumulative incidence and survival of thrombotic events in patients with classic PNH were determined. Results: The detection rate of MUC4 gene mutations in patients with classic PNH who experienced thrombotic events (thrombotic group) was 68.8% (11/16), which was significantly higher than that in the non-thrombotic group [10.3% (3/29) ] (P<0.001). All mutations occurred in exon 2. MUC4 mutation (OR=20.815, P=0.010) was identified as an independent risk factor for thrombotic events in patients with classic PNH. The cumulative incidence of thrombotic events was 78.6% (11/14) in the MUC4 gene mutation group (mutation group) and 16.1% (5/31) in the non-mutation group, showing a statistically significant difference between the two groups (P<0.001). Survival analysis showed a lower overall survival (OS) rate in the thrombotic group compared with that in the non-thrombotic group [ (34.4±25.2) % vs. (62.7±19.3) % ] (P=0.045). The OS rate of patients was (41.7±29.9) % in the mutation group and (59.1±18.3) % in the non-mutation group (P=0.487) . Conclusion: MUC4 gene mutations are associated with an increased incidence of thrombotic events in classic PNH patients, highlighting their role as independent risk factors for thrombosis in this population. These mutations can be considered a novel predictive factor that aids in evaluating the risk of thrombosis in patients with classic PNH.

Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype.

Deficiency of antithrombin increases risk of venous thromboembolism. We hypothesized that antithrombin deficiency affects fibrin clot structure and function. We evaluated 148 patients (age: 38 [32-50] years; 70% women) with genetically confirmed antithrombin deficiency and 50 healthy controls. Fibrin clot permeability (Ks) and clot lysis time (CLT) along with thrombin generation capacity were assessed before and after antithrombin activity normalization in vitro. Antithrombin-deficient patients had lower antithrombin activity (-39%) and antigen levels (-23%) compared with controls (both p < 0.01). Prothrombin fragment 1 + 2 levels were 26.5% higher in patients with antithrombin deficiency than in controls along with 94% increased endogenous thrombin potential (ETP) and 108% higher peak thrombin (all p < 0.01). Antithrombin deficiency was associated with 18% reduced Ks and 35% prolonged CLT (both p < 0.001). Patients with type I (n = 65; 43.9%) compared with type II antithrombin deficiency (n = 83; 56.1%) had 22.5% lower antithrombin activity (p < 0.001) and despite similar fibrinogen levels, 8.4% reduced Ks, 18% prolonged CLT, and 30% higher ETP (all p < 0.01). Reduced Ks was associated with lower antithrombin antigen level (β = - 6.1, 95% confidence interval [CI]: -1.7 to -10.5), while prolonged CLT was associated with lower antithrombin antigen (β = - 69.6, 95% CI: -9.6 to -129.7), activity (β = - 2.4, 95% CI: -0.3 to -4.5), higher PAI-1 (β = 12.1, 95% CI: 7.7-16.5), and thrombin-activatable fibrinolysis inhibitor levels (β = 3.8, 95% CI: 1.9-5.7). Addition of exogenous antithrombin reduced ETP (-42%) and peak thrombin (-21%), and improved Ks (+8%) and CLT (-12%; all p < 0.01). Our study suggests that enhanced thrombin generation and prothrombotic plasma fibrin clot phenotype can contribute to increased risk of thrombosis in patients with antithrombin deficiency.

The novel left atrial appendage strain parameters are associated with thrombosis risk in patients with non-valvular atrial fibrillation.

We sought to explore a novel left atrial appendage (LAA) strain parameter which could represent the cumulative adverse impact of chronic Atrial fibrillation (AF) on the LAA function, and the relationship between the LAA strain parameter and thrombosis risk in patients with non-valvular AF. We enrolled 268 patients with non-valvular AF and 58 sinus rhythm subjects who underwent transesophageal echocardiography in the study. LAA longitudinal strain amplitude (LAA LSA) was defined as the sum of the value of the maximum positive peak strain (LAA PLS) and the absolute value of the minimum negative peak strain (LAA NLS). Dense spontaneous echo contrast (SEC) was defined as grade 3 or 4 SEC. Compared to sinus rhythm group, the global LAA strain parameters were significantly lower in paroxysmal AF (n = 148), and the lowest of them were found in persistent AF (n = 120), which suggested that the global LAA strain parameters could evaluate LAA function in sinus rhythm, paroxysmal AF and persistent AF. Compared with patients in AF without SEC/thrombus (n = 113), the regional and global LAA strain parameters were significantly depressed in AF with SEC/thrombus (n = 155). Multivariate logistic regression analyses showed that LAA global LSA (OR 0.768; 95% CI:0.569, 0.970; p = 0.027) was an independent predicter of the SEC/thrombus. Compared with patients in AF without dense SEC or thrombus (n = 210), the regional and global LAA strain parameters were significantly impaired in the patients with dense SEC/thrombus(n = 58). LAA global LSA (AUC 0.884) had the best predictable accuracy for dense SEC or thrombus, and outperformed LAA PLS, LAA NLS, CHA2DS2-VASc score and conventional LAA functional parameters that have been used in the evaluation blood flow stasis in LAA. LAA LSA showed excellent interobserver and intra-observer agreement beyond LAA PLS and LAA NLS. The novel LAA strain parameters, which were feasible and reproducible parameters for evaluation LAA mechanic function, had good predictive accuracy for blood flow stasis in LAA beyond conventional LAA functional parameters.

Controversies in the Management of Antiphospholipid Syndrome.

Strategies to prevent thrombosis in antiphospholipid antibody (aPL)-positive patients are of the utmost importance. The risk of thrombosis in patients with aPLs varies, depending on additional venous thrombosis and cardiovascular risk factors, as well as associated comorbidities. Recurrent thrombosis despite treatment with vitamin K antagonists is relatively common in daily practice. In this context, the effectiveness of the new direct oral anticoagulants in antiphospholipid syndrome is debated, as well as that of low-dose aspirin for primary thromboprophylaxis. There is an urgent unmet need to recognize the subgroup of patients that may benefit from low-dose aspirin use. Here we also discuss different points of view on primary and secondary thrombosis preventions in aPL-positive patients, which were presented as a debate during the 2021 PANLAR Congress (Pan-American League of the Association of Rheumatology) and that was organized by GESAF (Argentine Society of Rheumatology APS Study Group). It is the intention of this article to provide a useful discussion to aid treatment decision-making in daily clinical practice.

Bidirectional effects of oral anticoagulants on gut microbiota in patients with atrial fibrillation.

The imbalance of gut microbiota (GM) is associated with a higher risk of thrombosis in patients with atrial fibrillation (AF). Oral anticoagulants (OACs) have been found to significantly reduce the risk of thromboembolism and increase the risk of bleeding. However, the OAC-induced alterations in gut microbiota in patients with AF remain elusive. In this study, the microbial composition in 42 AF patients who received long-term OAC treatment (AF-OAC group), 47 AF patients who did not (AF group), and 40 volunteers with the risk of AF (control group) were analyzed by 16S rRNA gene sequencing of fecal bacterial DNA. The metagenomic functional prediction of major bacterial taxa was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software package. The gut microbiota differed between the AF-OAC and AF groups. The abundance of Bifidobacterium and Lactobacillus decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as Megamonas. In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus Ruminococcus but increased certain potential pathogenic taxa, such as genera Streptococcus, Escherichia-Shigella, and Klebsiella. The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that Bacteroidetes, Brucella, and Ochrobactrum were more abundant in the anticoagulated bleeding AF patients, Akkermansia and Faecalibacterium were more abundant in the non-anticoagulated-bleeding-AF patients. The neutrophil-to-lymphocyte ratio (NLR) was lower in the AF-OAC group compared with the AF group (P < 0.05). Ruminococcus was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score (P < 0.05), and the OACs-enriched species (Megamonas and Actinobacteria) was positively correlated with the prothrombin time (PT) (P < 0.05). Ruminococcus and Roseburia were negatively associated with bleeding events (P < 0.05). Our study suggested that OACs might benefit AF patients by reducing the inflammatory response and modulating the composition and abundance of gut microbiota. In particular, OACs increased the abundance of some gut microbiota involved in bleeding and gastrointestinal dysfunction indicating that the exogenous supplementation with Faecalibacterium and Akkermansia might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.

Immune Checkpoint Inhibitors-Associated Thrombosis: Incidence, Risk Factors and Management.

Immune checkpoint inhibitors (ICIs) target programmed cell death (PD) 1 receptor and its ligand PD-L1, and have become an integral part of treatment regimens in many cancers including lung cancer, renal cell carcinoma, melanoma, and more. Cancer is associated with a significantly increased risk of venous thromboembolism compared to non-cancer patients, and the risks increase further with anticancer therapies including ICIs. Cancer-associated thrombosis can lead to hospitalizations, delayed cancer treatment, and mortality. While thrombosis was not reported as a major complication in initial clinical trials leading to the approval of ICIs, emerging evidence from post-marketing studies revealed concerning risks of thrombosis in patients receiving ICIs. However, results remained heterogenous given differences in study designs and populations. Recent studies also showed that C-reactive protein dynamics might be an easily accessible biomarker for thrombosis and disease response in this population. In addition, early findings indicated that a commonly used anticoagulant for cancer-associated thrombosis, factor Xa inhibitors, might have potential synergistic antitumor effects when combined with ICIs. Herein we will review the current literature on the incidence, risk factors, and management of thrombosis in patients with cancer receiving ICIs. We aim to provide valuable information for clinicians in managing these patients.

Determination of Deep Vein Thrombosis Risk in Patients Staying in an Orthopedics and Traumatology Clinic

Background: Deep vein thrombosis (DVT) is an important life-threatening complication in patients having orthopedic surgery and its risk factors are still debatable. &#x0D; Aim: This study aimed to determine preoperative and postoperative DVT risk, its risk factors and their effects on preoperative and postoperative DVT risk scores in patients having orthopedic surgery and staying in an orthopedics and traumatology clinic.&#x0D; Method: This descriptive, cross-sectional study was performed with 244 patients. Data were gathered with a sociodemographic, health status and prophylaxis for DVT form and the Autar Deep Vein Thrombosis Risk Assessment Scale (Autar DVTRAS).&#x0D; Results: There was a strong significant difference between the preoperative and postoperative mean scores for the Autar DVTRAS (p