OBJECTIVE:We performed a meta-analysis to investigate benefits and harms of chemoprophylaxis among surgical patients individually risk stratified for venous thromboembolism (VTE) using Caprini ...scores.
SUMMARY OF BACKGROUND DATA:Individualized VTE risk stratification may identify high risk surgical patients who benefit from peri-operative chemoprophylaxis.
METHODS:MEDLINE, EMBASE, and the Cochrane Library (CENTRAL) databases were queried. Eligible studies contained data on postoperative VTE and/or bleeding events with and without chemoprophylaxis. Primary outcomes included rates of VTE and clinically relevant bleeding after surgical procedures, stratified by Caprini score. A meta-analysis was conducted using a random-effects model.
RESULTS:Among 13 included studies, 11 (n = 14,776) contained data for VTE events and 8 (n = 7590) contained data for clinically relevant bleeding with and without chemoprophylaxis. The majority of patients received mechanical prophylaxis. A 14-fold variation in VTE risk (from 0.7% to 10.7%) was identified among surgical patients who did not receive chemoprophylaxis, and patients at increased levels of Caprini risk were significantly more likely to have VTE. Patients with Caprini scores of 7 to 8 odds ratio (OR) 0.60, 95% confidence interval (95% CI) 0.37–0.97 and >8 (OR 0.41, 95% CI 0.26–0.65) had significant VTE risk reduction after surgery with chemoprophylaxis. Patients with Caprini scores ≤6 comprised 75% of the overall population, and these patients did not have a significant VTE risk reduction with chemoprophylaxis. No association between postoperative bleeding risk and Caprini score was identified.
CONCLUSIONS:The benefit of peri-operative VTE chemoprophylaxis was only found among surgical patients with Caprini scores ≥7. Precision medicine using individualized VTE risk stratification helps ensure that chemoprophylaxis is used only in appropriate surgical patients and may minimize bleeding complications.
Objective
Antiphospholipid syndrome (APS) is a leading acquired cause of thrombotic events. Although antiphospholipid antibodies have been shown to promote thrombosis in mice, the role of neutrophils ...has not been explicitly studied. The aim of this study was to characterize neutrophils in the context of a new model of antiphospholipid antibody–mediated venous thrombosis.
Methods
Mice were administered fractions of IgG obtained from patients with APS. At the same time, blood flow through the inferior vena cava was reduced by induction of stenosis. Resulting thrombi were characterized for size and neutrophil content. Circulating factors and the vessel wall were also assessed.
Results
As measured by both thrombus weight and thrombosis frequency, mice treated with IgG from patients with APS (APS IgG) demonstrated exaggerated thrombosis as compared with control IgG–treated mice. Thrombi in mice treated with APS IgG were enriched for citrullinated histone H3 (a marker of neutrophil extracellular traps NETs). APS IgG–treated mice also demonstrated elevated levels of circulating cell‐free DNA and human IgG bound to the neutrophil surface. In contrast, circulating neutrophil numbers and markers of vessel wall activation were not appreciably different between APS IgG–treated mice and control mice. Treatment with either DNase (which dissolves NETs) or a neutrophil‐depleting antibody reduced thrombosis in APS IgG–treated mice to the level in control mice.
Conclusion
These data support a mechanism whereby circulating neutrophils are primed by antiphospholipid antibodies to accelerate thrombosis. This line of investigation suggests new, immunomodulatory approaches for the treatment of APS.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Venous thromboembolism (VTE) is a pathology encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with high morbidity and mortality. Because patients often present after a ...thrombus has already formed, the mechanisms that drive DVT resolution are being investigated in search of treatment. Herein, we review the current literature, including the molecular mechanisms of fibrinolysis and collagenolysis, as well as the critical cellular roles of macrophages, neutrophils, and endothelial cells. We propose two general models for the operation of the immune system in the context of venous thrombosis. In early thrombus resolution, neutrophil influx stabilizes the tissue through NETosis. Meanwhile, macrophages and intact neutrophils recognize the extracellular DNA by the TLR9 receptor and induce fibrosis, a complimentary stabilization method. At later stages of resolution, pro-inflammatory macrophages police the thrombus for pathogens, a role supported by both T-cells and mast cells. Once they verify sterility, these macrophages transform into their pro-resolving phenotype. Endothelial cells both coat the stabilized thrombus, a necessary early step, and can undergo an endothelial-mesenchymal transition, which impedes DVT resolution. Several of these interactions hold promise for future therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Venous thrombosis (VT), a leading cause of morbidity and mortality worldwide, has recently been linked to neutrophil activation and release of neutrophil extracellular traps (NETs) via a process ...called NETosis. The use of various in vivo thrombosis models and genetically modified mice has more precisely defined the exact role of NETosis in the pathogenesis of VT. Translational large animal VT models and human studies have confirmed the presence of NETs in pathologic VT. Activation of neutrophils, with subsequent NETosis, has also been linked to acute infection. This innate immune response, while effective for bacterial clearance from the host by formation of an intravascular bactericidal "net," also triggers thrombosis. Intravascular thrombosis related to such innate immune mechanisms has been coined immunothrombosis. Dysregulated immunothrombosis has been proposed as a mechanism of pathologic micro- and macrovascular thrombosis in sepsis and autoimmune disease. In this focused review, we will address the dual role of NETs in the pathogenesis of VT and immunothrombosis.
Mechanisms of Venous Thrombosis and Resolution Wakefield, Thomas W; Myers, Daniel D; Henke, Peter K
Arteriosclerosis, thrombosis, and vascular biology,
2008-March, 2008-Mar, 2008-03-00, 20080301, Volume:
28, Issue:
3
Journal Article
Peer reviewed
Open access
Venous thromboembolism is a significant health care problem in the US. In this review, the unique role of inflammation to the venous thrombotic process is emphasized as well as the potential role of ...abnormalities of fibrinolytic mechanisms to the thrombotic process. Inflammation influences not only thrombogenesis but also thrombus resolution and vein wall remodeling, and these interactions are also discussed. Knowledge of molecular and immunologic mechanisms for venous thrombosis and its resolution should allow for the future development of targeted therapies.
IMPORTANCE: Appropriate risk stratification for venous thromboembolism (VTE) is essential to providing appropriate thromboprophylaxis and avoiding morbidity and mortality. OBJECTIVE: To validate the ...Caprini VTE risk assessment model in a previously unstudied high-risk cohort: critically ill surgical patients. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of 4844 adults (≥18 years old) admitted to a 20-bed surgical intensive care unit in a large tertiary care academic hospital during a 5-year period (July 1, 2007, through June 30, 2012). MAIN OUTCOMES AND MEASURES: The main study outcome was VTE (defined as patients with deep vein thrombosis or pulmonary embolism) that occurred during the patient’s initial hospital admission. RESULTS: The study population was distributed among risk levels as follows: low, 5.3%; moderate, 19.9%; high, 31.6%; highest, 25.4%; and superhigh, 14.9%. The overall incidence of inpatient VTE was 7.5% and increased with risk level: 3.5% in low-risk patients, 5.5% in moderate-risk patients, 6.6% in high-risk patients, 8.6% in highest-risk patients, and 11.5% in superhigh-risk patients. Patients with Caprini scores greater than 8 were significantly more likely to develop inpatient VTE events when compared with patients with Caprini scores of 7 to 8 (odds ratio OR, 1.37; 95% CI, 1.02-1.85; P = .04), 5 to 6 (OR, 1.35; 95% CI, 1.16-1.57; P < .001), 3 to 4 (OR, 1.30; 95% CI, 1.16-1.47; P < .001), or 0 to 2 (OR, 1.37; 95% CI, 1.16-1.64; P < .001). Similarly, patients with Caprini scores of 7 to 8 were significantly more likely to develop inpatient VTE when compared with patients with Caprini scores of 5 to 6 (OR, 1.33; 95% CI, 1.01-1.75; P = .04), 3 to 4 (OR, 1.27; 95% CI, 1.08-1.51; P = .005), or 0 to 2 (OR, 1.38; 95% CI, 1.10-1.74; P = .006). CONCLUSIONS AND RELEVANCE: The Caprini VTE risk assessment model is valid. This study supports the use of individual risk assessment in critically ill surgical patients.
Validate a retrospective venous thromboembolism (VTE) risk scoring method, which was developed at the University of Michigan Health System and based on the Caprini risk assessment model, and assess ...the confounding effects of VTE prophylaxis.
Assessing patients for risk of VTE is essential to initiating appropriate prophylaxis and reducing the mortality and morbidity associated with deep vein thrombosis and pulmonary embolism.
VTE risk factors were identified for 8216 inpatients from the National Surgical Quality Improvement Program using the retrospective scoring method. Logistic regression was used to calculate odds ratios (OR) for VTE within 30 days after surgery for risk factors and risk level. A bivariate probit model estimated the effects of risk while controlling for adherence to prophylaxis guidelines.
Distribution of the study population by risk level was highest, 52.1%; high, 36.5%; moderate, 10.4%; and low, 0.9%. Incidence of VTE within 30 days was overall 1.4%; by risk level: highest, 1.94%; high, 0.97%; moderate, 0.70%; low, 0%. Controlling for length of hospitalization (>2 d) and fiscal year, pregnancy or postpartum (OR = 8.3; 1.0-68, P < 0.05), recent sepsis (4.0; 1.4-10.9, P < 0.01), malignancy (2.3; 1.5-3.3, P < 0.01), history of VTE (2.1; 1.1-4.1, P < 0.05), and central venous access (1.8; 1.1-3.0, P < 0.05) were significantly associated with VTE. Risk level was significantly associated with VTE (1.9; 1.3-2.6, P < 0.01). The bivariate probit demonstrated significant correlation between the probability of VTE and lack of adherence to prophylaxis guidelines (rho = 0.299, P = 0.013).
The retrospective risk scoring method is valid and supports use of individual patient assessment of risk for VTE within 30 days after surgery.
Deep vein thrombosis and pulmonary embolism are a significant health care concern, representing a major source of mortality and morbidity. In order to understand the pathophysiology of thrombogenesis ...and thrombus resolution, animal models are necessary. Mouse models of venous thrombosis contribute to our understanding of the initiation, propagation, and resolution of venous thrombus, as well as allow for the evaluation of new pharmaceutical approaches to prophylaxis and treatment of deep vein thrombosis. In this work we review the ferric chloride model, the inferior vena cava ligation model, the inferior vena cava stenosis models, and the electrolytic inferior vena cava model and compare their advantages and disadvantages.
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