Primary Prevention Of Venous Thromboembolism Research Articles

Statins for the primary prevention of venous thromboembolism.

Venous thromboembolism (VTE) involves the formation of a blood clot in a vein, and includes deep venous thrombosis (DVT) or pulmonary embolism (PE). The annual incidence for VTE varies from 0.75 to 2.69 per 1000 individuals, with about 40 million people worldwide impacted by VTE. Statins, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors, inhibit cholesterol biosynthesis and display several vascular-protective effects, including antithrombotic properties. However, the potential role of statins in the primary prevention of VTE is still not clear. To evaluate the benefits and risks of statins in preventing venous thromboembolism (VTE) in individuals with no prior history of VTE. We used standard Cochrane search methods. The search was last updated on 13 March 2023. We included randomized controlled trials (RCTs) comparing statins with any control intervention (including placebo and usual care) in healthy individuals or participants with conditions other than VTE. There were no restrictions on the dose, duration, route, or timing of statins. We used standard Cochrane methods. Our primary outcomes were VTE, DVT, and PE. Our secondary outcomes were serious adverse events, adverse events, and mortality. We used the trial sequential analysis (TSA) method to judge whether the evidence was sufficient, and we used the GRADE approach to assess the certainty of the evidence for each outcome. We included 27 RCTs involving 122,601 adults (aged 18 years and above) who were healthy, had various medical conditions (e.g. hypercholesterolemia), or were at risk for cardiovascular disease. Both males and females were included in all studies. Two studies focused solely on participants over 60 years of age. We deemed four studies to have a low risk of bias overall, while 19 were at high risk of bias, and four were unclear. The 27 studies compared use of statins versus placebo or usual care in individuals who had never experienced VTE. The statins used in the studies were atorvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, and simvastatin. Twenty-three studies followed up participants for over a year, with six of those extending follow-ups for over five years. Twenty-five studies were based in hospitals, and 24 studies were funded by industry. Only one study used VTE as a primary endpoint. The median incidence of VTE in the statins group was 0.72% (ranging from 0% to 10.53%), and in the control group it was 0.89% (ranging from 0% to 6.83%). Our pooled analysis of the 27 studies showed that, relative to control groups, statins may slightly reduce the overall incidence of VTE (odds ratio (OR) 0.86, 95% confidence intervals (CI) 0.76 to 0.98; 27 studies, 122,601 participants; low-certainty evidence). Of the statins we evaluated, only rosuvastatin seemed to be associated with a reduced incidence of VTE, albeit the reduction in incidence was very small. The evidence did not clearly indicate a difference between groups in the incidence of DVT (OR 0.70, 95% CI 0.41 to 1.18; six studies, 40,305 participants; low-certainty evidence), PE (OR 0.83, 95% CI 0.46 to 1.52; five studies, 28,427 participants; low-certainty evidence), or myopathy (OR 1.10, 95% CI 0.83 to 1.45; 10 studies, 75,551 participants; low-certainty evidence). Nonetheless, statin use might slightly decrease the incidence of any serious adverse event (OR 0.95, 95% CI 0.91 to 0.99; 13 studies, 67,020 participants; low-certainty evidence) and any death (OR 0.90, 95% CI 0.86 to 0.95; 24 studies, 116,761 participants; low-certainty evidence), compared to control. Using statins for the primary prevention of VTE may slightly reduce the incidence of VTE and all-cause mortality. However, this effect is likely too weak to be considered significant. Statin use may not decrease the occurrence of DVT and PE. The current evidence is insufficient to draw strong conclusions because of the risk of bias in the studies, imprecision in the effect estimates, and potential publication bias. More evidence from well conducted and fully reported RCTs is needed to assess the preventive effects of different types of statins, as well as the effects of different dosages and treatment durations in various populations.

Primary prevention of venous thromboembolic complications in spinal cord injury: modern concepts

Venous thromboembolism is a common complication following spinal cord injury that can significantly aggravate a pre-existing condition and lead to a death. Patients who suffer acute spinal cord injury have a higher prevalence of venous thromboembolism than patients who suffer other traumatic injuries with sparing of the spinal cord. It is important for physical medicine and rehabilitation specialists to have knowledge аbout primary prevention of venous thromboembolism in patients with acute, subacute and chronic spinal cord injury. This article provides a brief overview of typical venous thromboembolism frequency (leg deep vein thrombosis and pulmonary embolism), pathogenesis peculiarities, venous thromboembolism risk factors and diagnostic considerations. The main attention is given to the primary thromboprophylaxis (methods and duration) depending on the spinal cord injury period and the spinal cord injury level. Further studies are required to clarify the optimal prophylaxis methods and protocols to prevent venous thromboembolism following spinal cord injury.

Statins use and recurrent venous thromboembolism in the direct oral anticoagulant era: insight from the COMMAND VTE Registry-2.

Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45-0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59-1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era.

Statins during Anticoagulation for Emergency Life-Threatening Venous Thromboembolism: A Review.

Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors-the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death.

Lipid lowering for prevention of venous thromboembolism: a network meta-analysis.

Studies have suggested that statins may be associated with reduced risk of venous thromboembolism (VTE). The aim of the current study was to assess the evidence regarding the comparative effect of all lipid-lowering therapies (LLT) in primary VTE prevention. After a systematic search of PubMed, CENTRAL, and Web of Science up until 2 November 2022, randomized controlled trials (RCT) of statins (high- or low-/moderate-intensity), ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were selected. An additive component network meta-analysis to compare VTE risk during long-term follow-up across different combinations of LLT was performed. Forty-five RCTs (n = 254 933 patients) were identified, reporting a total of 2084 VTE events. Compared with placebo, the combination of PCSK9i with high-intensity statin was associated with the largest reduction in VTE risk (risk ratio [RR] 0.59; 95% confidence interval [CI] 0.43-0.80), while there was a trend towards reduction for high-intensity (0.84; 0.70-1.02) and low-/moderate-intensity (0.89; 0.79-1.00) statin monotherapy. Ezetimibe monotherapy did not affect the VTE risk (1.04; 0.83-1.30). There was a gradual increase in the summary effect of VTE reduction with increasing intensity of the LLT. When compared with low-/moderate-intensity statin monotherapy, the combination of PCSK9i and high-intensity statin was significantly more likely to reduce VTE risk (0.66; 0.49-0.89). The present meta-analysis of RCTs suggests that LLT may have a potential for VTE prevention, particularly in high-intensity dosing and in combination therapy.

Primary prevention of venous thromboembolism with low molecular weight heparins in surgical patients – 2024: Council of Experts resolution

On March 15, 2024, in Moscow, the Russian Phlebological Association and the National Association of Specialists in Thrombosis, Clinical Hemostasiology and Hemorheology organized a meeting of the Council of Experts during the Russian Forum on Thrombosis and Hemostasis on the acute issues of venous thromboembolism (VTE) primary prevention using low molecular weight heparins (LMWH) in surgical patients with different body weight. The participants reviewed the relevance and prevalence of this problem in surgical practice, discussed risk factors and the frequency of VTE development, including bleeding in the postoperative period, and the Caprini risk score for complications. The discussion also focused on standard and personalized LMWH doses for primary prophylaxis of VTE in the perioperative period in surgical patients, depending on body weight, and the role of laboratory tests, including assessment of LMWH anti-Xa activity for monitoring the efficacy and safety of VTE primary prevention in clinical practice.

Risk of recurrent venous thromboembolism in cancer patients after discontinuation of anticoagulant therapy

Anticoagulant therapy is recommended for cancer-related venous thromboembolism (VTE). Recurrent VTE prevention is the main goal of this treatment. The majority of evidence-based practice guidelines recommend anticoagulant treatment for at least 6 months. Based on individual assessment of potential benefits and risks, tolerability, drug availability, patient preference, and cancer activity, active cancer patients should continue anticoagulant treatment beyond the 6-month course. When cancer is no longer active or the risk outweighs the benefit, anticoagulant therapy is usually stopped after 3-6 months. Until recently, there was little data on the risk of recurrent VTE in cancer-associated VTE patients after stopping anticoagulants. New results and evidence synthesis have emerged in the last 3 years. Recurring VTE occurs in over 30% in the 5 years after treatment discontinuation. In the first six months, recurrence rates are 10-15%. Recurrences reach 31% at 2 years and stabilize between 2 and 5. Duration of prior anticoagulation does not affect cumulative recurrence. The high risk of recurrent VTE after discontinuing treatment supports guidelines to continue anticoagulant treatment if cancer is active. Stopping anticoagulants after 3-6 months may not be ideal, so randomized clinical trials should be conducted quickly. This review highlights the need to improve cancer patients' primary VTE prevention efforts.

Primary prevention of venous thromboembolism in ambulatory cancer patients: recent advances and practical implications.

Venous thromboembolism (VTE) is a common complication in ambulatory cancer patients receiving anticancer therapies. Many patient-, cancer-, and treatment‑related factors along with specific biomarkers can be associated with an increased risk of VTE in patients with cancer. Risk assessment models, such as the Khorana score, serve as valuable tools to aid in the identification of patients with cancer who are at high risk of VTE. Two randomized controlled trials have evaluated the efficacy of primary thromboprophylaxis with low‑dose direct oral anticoagulants, apixaban and rivaroxaban, to reduce the risk of VTE in ambulatory patients with cancer who are at intermediate to high risk of VTE identified by the Khorana score. This narrative review summarizes the literature on the risk factors and risk assessment process for VTE, and the use of primary thromboprophylaxis in ambulatory cancer patients. We also outline important practical considerations for initiating primary thromboprophylaxis in this population.

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study.

Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.

Development and Validation of a Clinical Prediction Model for Venous Thromboembolism Following Neurosurgery: A 6-Year, Multicenter, Retrospective and Prospective Diagnostic Cohort Study.

Based on the literature and data on its clinical trials, the incidence of venous thromboembolism (VTE) in patients undergoing neurosurgery has been 3.0%~26%. We used advanced machine learning techniques and statistical methods to provide a clinical prediction model for VTE after neurosurgery. All patients (n = 5867) who underwent neurosurgery from the development and retrospective internal validation cohorts were obtained from May 2017 to April 2022 at the Department of Neurosurgery at the Sanbo Brain Hospital. The clinical and biomarker variables were divided into pre-, intra-, and postoperative. A univariate logistic regression (LR) was applied to explore the 67 candidate predictors with VTE. We used a multivariable logistic regression (MLR) to select all significant MLR variables of MLR to build the clinical risk prediction model. We used a random forest to calculate the importance of significant variables of MLR. In addition, we conducted prospective internal (n = 490) and external validation (n = 2301) for the model. Eight variables were selected for inclusion in the final clinical prediction model: D-dimer before surgery, activated partial thromboplastin time before neurosurgery, age, craniopharyngioma, duration of operation, disturbance of consciousness on the second day after surgery and high dose of mannitol, and highest D-dimer within 72 h after surgery. The area under the curve (AUC) values for the development, retrospective internal validation, and prospective internal validation cohorts were 0.78, 0.77, and 0.79, respectively. The external validation set had the highest AUC value of 0.85. This validated clinical prediction model, including eight clinical factors and biomarkers, predicted the risk of VTE following neurosurgery. Looking forward to further research exploring the standardization of clinical decision-making for primary VTE prevention based on this model.

Comparison of the Efficacy and Safety of Rivaroxaban and Low Molecular Heparin in Preventing Venous Thromboembolism in Inpatient Cancer Patients.

There are few studies on using rivaroxaban and low molecular heparin (LMWH) to prevent venous thromboembolism (VTE) in hospitalized cancer patients. We conducted a retrospective study to evaluate the efficacy and safety of rivaroxaban versus LMWH for the primary prevention of VTE in inpatient cancer patients. Information on patients was collected through 6-month follow-up and medical record inquiries. Clinical outcomes included VTE, total bleeding, thrombosis, major bleeding, minor bleeding, all-cause death, and a composite endpoint of bleeding, thrombosis, and death. A total of 602 hospitalized cancer patients were included in this study. During 6 months of follow-up, there were 26 VTE events (8.6%), 42 total bleeding events (7.0%), 62 all-cause deaths (10.3%), and 140 composite endpoints (23.3%). After adjusting for various confounding factors, there were no significant differences between the rivaroxaban and LMWH for VTE events (OR = 0.851, 95% CI [0.387-1.872], P=0.688), total bleeding (OR = 1.690, 95% CI [0.768-3.719], P = 0.192], thrombosis events (OR = 0.919, 95% CI [0.520-1.624], P = 0.772], major bleeding (OR = 0.276, 95% CI [0.037-2.059], P = 0.209), all-cause death (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), and composite endpoints (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), while minor bleeding (OR = 3.661 95% CI [1.000-7.083], P = 0.050) was significantly higher in the rivaroxaban than in the LMWH. In thromboprophylaxis in inpatient cancer patients, rivaroxaban has a similar rate of VTE and bleeding events as LMWH. Our results may provide a reference for the clinical use of rivaroxaban to prevent VTE in hospitalized cancer patients.

Autoimmune Hemolytic Anemia and Increased Stroke Risk in the United States: A Population-Based Study

Introduction Autoimmune hemolytic anemia (AIHA) is a clinically heterogeneous collection of disorders characterized by the presence of autoantibodies against the patient's erythrocytes. AHIA has been associated with an increased risk of thromboembolic events, including stroke. A recent nationwide cohort study from Denmark and France showed an increased risk of ischemic stroke compared to the general population. However, no extensive studies have been done in the United States (US); hence, we conducted a study of stroke and AIHA in the US population. Methods This is a retrospective study from 1999 to 2022. We analyzed data from a nationwide commercial database (Explorys, IBM) that aggregates records from 26 healthcare systems spread over 50 states with almost 80 million patients. It is a cloud-based platform in which participating institutions provide de-identified data from electronic health records. Pooled data is then standardized and normalized. Explorys uses Systemized Nomenclature of Medicine - Clinical Terms (SNOMED CT) coding for medical diagnosis. We identified adult patients (over 18 years old) with the diagnosis of AIHA. Patients with stroke were identified with the following SNOMED-CT diagnosis "cerebrovascular accidents''. In addition, we obtained information on risk factors for stroke, including sex, age over 65 years, and comorbidities known to be a risk factor, including hypertension, atrial fibrillation, diabetes mellitus, hyperlipidemia, smoking, and obesity.Multivariable logistic regression adjusting for all covariates was created to test for stroke. Results were presented as odds ratio (OR) with a corresponding 95% confidence interval (CI). All tests were two-sided, and a p-value ≤ 0.01 was considered statistically significant. Results An adult population of 69,339,860 were included. AHIA was diagnosed in 12,800 patients (less than 1 per 100,000) and stroke was diagnosed in 238,860 (0.34%). AIHA population characteristics were; females 7,720 (60%), age over 65 years 7,510 (59%), stroke 260 (2%), hypertension 8,260 (65%), hyperlipidemia 6,580 (51%), diabetes mellitus 4,030 (31%), obesity 3,080 (24%), atrial fibrillation 2,650 (21%), and smoking 1,080 (14%). Baseline characteristics are shown in table 1. Statically significant OR of covariates tested is as follows; hypertension OR 9.35 (95% CI 9.22-9.49), AHIA OR 2.75 (95% CI 2.49 - 3.01), atrial fibrillation OR 2.59 (95% CI 2.57 - 2.62), diabetes mellitus 2.44 (95% CI 2.42, 2.47), hyperlipidemia OR 1.96 (95% CI 1.94, 1.98), smoking OR 1.5 (95% CI 1.94, 1.98), age over 65 years OR 1.19 (95% CI 1.18, 1.20), and male OR 0.85 (95% CI 0.84, 0.85). Multivariable logistic regression of factors associated with stroke is shown in table 2. Discussion and conclusion This is the largest population-based study analyzing the association between AIHA and stroke, and we included the most relevant confounding risk factors in our analysis. As expected, the strongest risk factor associated with stroke was hypertension. What was surprising was that AIHA followed it as the second strongest risk factor, which exceeded atrial fibrillation as a risk factor. Limitations of the retrospective design of the study are numerous. They include lack of patient-level data, the subtype of stroke, the subtype of AIHA, the severity of AIHA, temporality, medications used, and their implications on stroke risk, and inaccuracies in coding. A potential explanation for increased thrombosis includes depletion of nitric oxide as a consequence of intravascular hemolysis with resultant enhanced platelet adhesions, and another possible mechanism is the release of procoagulant microparticles during hemolysis. While there is an ongoing trial looking into long-term apixaban in the primary prevention of venous thromboembolism in AIHA (NCT05089227), no active study is looking into minimizing stroke risk. Prospective studies to affirm association, risk stratifies patients, and ultimately test the utility of prophylactic anticoagulation are most needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Thromboinflammation in cardiovascular disease: lessons learned for the management of hypertension, heart failure, and aortic valve stenosis.

Thromboinflammation has emerged as a new term to describe the interconnection between the simultaneous activation of the coagulation and the immune system. It is the flipside of immunothrombosis, an evolutionary highly conserved mechanism of innate immunity that has developed to allow trapping and compartimentalization of invaded pathogens and to improve host defence. In contrast to immunothrombosis, it occurs in the absence of a pathogen, but is triggered mainly by endothelial dysfunction. This may lead to release of pro-inflammatory cytokines as well as chemokines and adhesion molecules, activation of myeloid cells, decryption of tissue factor on the surface of neutrophils and monocytes, release of von Willebrand factor (vWF) from platelets and endothelial cell Weibel–Palade bodies, and netting of neutrophils with consecutive activation of the contact phase of the coagulation cascade and FXa/thrombin activation, implying both thrombin propagation via the FXI feedback activation and increased fibrin deposition.1 In cardiovascular diseases (CVDs), paradigmatic conditions of thromboinflammation are endothelial erosion as a mechanism of acute coronary syndrome in the absence of plaque rupture [Type II myocardial infarction (MI)],2 deep vein thrombosis induced by low flow,3 and atherogenesis propelled by a chronically activated coagulation cascade.4 In some indications, recent advances in pharmacotherapy were successful in ameliorating the disease burden evoked by thromboinflammation. For example, long-term FXa inhibition can reduce thrombosis-associated morbidity and mortality in cancer, when administered for primary prevention of venous thromboembolism in selected patients,5 and low-dose rivaroxaban in addition to aspirin can lower major adverse cardiovascular events and all-cause mortality in patients with coronary artery disease who had an MI in the past.6 These findings of the COMPASS trial merit special consideration, because one-fourth of the anticoagulant dose of rivaroxaban was efficient for reaching this endpoint including reduction in thrombotic events, which has been attributed to vascular protection mediated through protease-activated receptor inhibition instead of reducing thrombin and fibrin formation in this population of non-atrial fibrillation patiens. The identification of the thrombin-FXI feedback amplification loop for thrombin propagation holds promise to avoid blood clotting without abolishing haemostasis and has sparked the development of novel FXI(a) inhibitors for safer anticoagulation7 that seamlessly align into the concept of thromboinflammation (Figure 1).

Cancer-associated venous thromboembolism

Cancer-associated thrombosis (including venous thromboembolism (VTE) and arterial events) is highly consequential for patients with cancer and is associated with worsened survival. Despite substantial improvements in cancer treatment, the risk of VTE has increased in recent years; VTE rates additionally depend on the type of cancer (with pancreas, stomach and primary brain tumours having the highest risk) as well as on individual patient's and cancer treatment factors. Multiple cancer-specific mechanisms of VTE have been identified and can be classified as mechanisms in which the tumour expresses proteins that alter host systems, such as levels of platelets and leukocytes, and in which the tumour expresses procoagulant proteins released into the circulation that directly activate the coagulation cascade or platelets, such as tissue factor and podoplanin, respectively. As signs and symptoms of VTE may be non-specific, diagnosis requires clinical assessment, evaluation of pre-test probability, and objective diagnostic testing with ultrasonography or CT. Risk assessment tools have been validated to identify patients at risk of VTE. Primary prevention of VTE (thromboprophylaxis) has long been recommended in the inpatient and post-surgical settings, and is now an option in the outpatient setting for individuals with high-risk cancer. Anticoagulant therapy is the cornerstone of therapy, with low molecular weight heparin or newer options such as direct oral anticoagulants. Personalized treatment incorporating risk of bleeding and patient preferences is essential, especially as a diagnosis of VTE is often considered by patients even more distressing than their cancer diagnosis, and can severely affect the quality of life. Future research should focus on current knowledge gaps including optimizing risk assessment tools, biomarker discovery, next-generation anticoagulant development and implementation science.

Anticoagulants after Discharge in Patients with COVID-19: What we Know at the End of 2021

This review discusses reasons for prolonged use of anticoagulants after discharge of patients with COVID-19 without additional indication for anticoagulation. Data regarding rate of thrombotic and thromboembolic complications in patients with COVID-19 after discharge from the hospital are presented. Large randomized controlled trials EXCLAIM, ADOPT, MAGELLAN, APEX and MARINER with prolonged use of anticoagulants in patients hospitalized with acute nonsurgical diseases before pandemia of COVID-19 are discussed. The first prospective randomized controlled trial MICHELLE with direct oral anticoagulant rivaroxaban in a dose 10 mg once daily after discharge of patients with COVID-19 with high risk at least venous thromboembolism are analyzed. It seems that the most relevant approach for the determination of indications for prolonged use of anticoagulants in doses dedicated for primary prevention of venous thromboembolism after discharge of patients with COVID-19 without apparent indication for anticoagulation is a modified IMPROVE VTE risk score with the addition of elevated in-hospital D-dimer level. And the most well-studied approach for anticoagulation in these patients is a direct peroral anticoagulant rivaroxaban 10 mg once daily for 35 (and possibly up to 45) days after discharge.

Primary Prevention of Venous Thromboembolism: Current State

Primary Prevention of Venous Thromboembolism: Current State

Effects of statins in primary and secondary prevention for venous thromboembolism events: A meta analysis

ObjectiveThe associations between statins use and incidence or recurrence of venous thromboembolism (VTE) are controversial. We aimed to conduct a meta-analysis to reconcile the conflicting results. MethodsWe searched PubMed, Embase and Cochrane Library for studies published from database inception until May 31, 2021. Cohort studies and Randomized Controlled Trials that reported incidence or recurrence of VTE using statins compared with placebo or non-statins were included for meta-analysis. ResultsA total of 43 studies comprising over 8.6 million participants were included for analysis. The median follow-up duration was 38.1 months. Compared with no statins treatment, statins appeared to have a protective effect in primary prevention of VTE (RR 0.78, 95% CI 0.72–0.85), but significant heterogeneity was found among included studies (I2 = 81%). Statins was also associated with a 26% reduced risk of recurrent VTE (RR 0.74, 95% CI 0.70–0.78), even in patients receiving anticoagulant therapy (RR 0.77, 95% CI 0.65–0.92). In patients with a history of VTE, statins was associated with a reduced risk of bleeding and all cause mortality. The NNT of statins to prevent one case of VTE in the cancer population, and one case of recurrent VTE in patients with a history of VTE was 103.1 and 90.7 person-years respectively. ConclusionIn high-risk patients, statins treatment may reduce the incidence of VTE. Statins can also reduce the risk of recurrent VTE and all-cause mortality in patients with a history of VTE.

Interventions for the primary prevention of venous thromboembolism for hip fracture surgery

Interventions for the primary prevention of venous thromboembolism for hip fracture surgery

Metabolomic Profile in Venous Thromboembolism (VTE).

Venous thromboembolism (VTE) is a condition comprising deep venous thrombosis (DVT) and pulmonary embolism (PE). The prevalence of this disease is constantly increasing and it is also a chief reason for morbidity. Therefore, the primary prevention of VTE remains a highly important public health issue. At present, its diagnosis generally relies on subjective clinical examination and ultrasound imaging. D-dimer is also used as a biomarker, but it is considered to be poorly specific and only moderately sensitive. There are also no reliable methods that could accurately guide the type of treatment and potentially identify patients who may benefit from more aggressive therapies without the risk of bleeding. The application of metabolomics profiling in the area of vascular diseases may become a turning point in early diagnosis and patient management. Among the most described metabolites possibly related to VTE are carnitine species, glucose, phenylalanine, 3-hydroxybutarate, lactic acid, tryptophan and some monounsaturated and polyunsaturated fatty acids. The cell response to acute PE was suggested to involve the uncoupling between glycolysis and oxidative phosphorylation. Despite technological advancement in the identification of metabolites and their alteration in thrombosis, we still do not understand the mechanisms and pathways responsible for the occurrence of observed alterations.

Do Sequential Compression Devices Prevent Venous Thromboembolism in Hospital Inpatients?

IntroductionAnticoagulants (AC) are commonly used for primary prevention of venous thromboembolism (VTE) in hospitalized patients. Mechanical methods of VTE prevention such as sequential compression devices (SCD) are used mostly in combination with AC or in patients with high risk of bleeding.ObjectiveTo determine if the use of SCD prevents VTE in medically ill hospitalized patients.MethodsAll Sparrow Main Hospital admissions from 04/01/2015 to 03/31/2016 were included and categorized according to the methods used for prevention of VTE- SCD only (SCD), anticoagulants only (AC), SCD & anticoagulants (BOTH), and none (NONE). We excluded patients less than 18 years of age and those with VTE on admission. Bivariate and multivariate regression analyses were conducted. To control for the selection bias of patients to SCD, AC or BOTH group, we performed propensity score matching. First, the propensity scores for SCD, AC, and BOTH were estimated using logistic regression. The 1-1 optimal matching method was used to find matched controls from patients without treatment. The matched samples are expected to mimic the randomized controlled trial.ResultsWe identified a total of 39,265 eligible patients for our study- 20,220 of them were on SCD for VTE prophylaxis, 2,397 had AC, 5,719 had BOTH, and 10,929 had NONE of the measures (Table 1). Out of them, 0.6% (n=246) developed VTE during their hospital stay- 50 patients in SCD group, 40 in AC, 126 in BOTH, and 20 in NONE group. Among patients in the SCD group, 0.2% developed VTE; 0.1% developed VTE in NONE group. VTE developed in 1.6% of cases in the AC group and 2.2% in BOTH group (Table 1).Among patients without VTE, mean age was 56 years (SD±20.3), 58% were females, and 55% were active/former smokers. Similarly, patients with VTE had mean age of 62.7 (SD± 16.4); 44.5% were females and 52.5% were smokers. Mean length of hospital stay was 4.3 days (SD±5.5) in patients without VTE compared to 11.5 days (SD±12.82).Before propensity score matching, analysis showed that the risk of VTE was not decreased in SCD group compared to NONE group (OR 1.22, 95% CI 0.65-2.29). However, propensity matching analysis actually showed that the odds of developing VTE decreased with SCD compared to NONE (OR 0.26; 95% CI 0.18-0.38).Multivariate analysis showed various cancer types were associated with higher odds of VTE while comparing SCD vs NONE (Table 2). Hodgkin lymphoma had the highest risk among them (OR 11.60; 95% CI 1.45-92.56), followed by esophageal cancer (OR 10.27; 95% CI 1.31-80.18), bladder cancer (OR 8.45; 95% CI 1.94-36.67), colon cancer (OR 5.93; 95% CI 1.36-25.70), myeloma (OR 5.85; 95% CI 1.27-26.86), and leukemia (OR 5.14; 95% CI 1.52-17.41). Increased length of stay also led to increased VTE (OR 1.90; 95% CI 1.64-2.19).ConclusionUse of SCD prevents VTE during hospital stay. However, other confounding factors may also play a significant role. More studies to define role of SCD in VTE prevention are needed. Regardless of the method used for prevention, increased length of stay is associated with increased risk of VTE. [Display omitted] DisclosuresDhakal:Graduation Medical Education, Inc., Michigan State University: Research Funding. Rayamajhi:Michigan State University, College of Education: Research Funding; Sparrow/MSU Center for Innovation and Research: Research Funding.