Venous Thromboembolism Risk Assessment and Prophylaxis: An Audit-Based Study

Venous thromboembolism prophylaxis: do trial results enable clinicians and patients to evaluate whether the benefits justify the risk? proceedings of an ad hoc working group meeting

See article, page 799

BackgroundOptimal thromboprophylaxis after cardiac surgery is uncertain. This systematic review aimed to define the incidence and risk factors for deep vein thrombosis (DVT), fatal and nonfatal pulmonary embolism (PE), and assess whether venous thromboembolism (VTE) prophylaxis was effective in reducing VTE without complications after cardiac surgery.Methods and ResultsTwo reviewers independently searched and assessed the quality and outcomes of randomized, controlled trials (RCTs) and observational studies on VTE after cardiac surgery in the MEDLINE, EMBASE, and Cochrane controlled trial register (1966 to December 2014). Sixty‐eight studies provided data on VTE outcomes or complications related to thromboprophylaxis after cardiac surgery. The majority of the studies were observational studies (n=49), 16 studies were RCTs, and 3 were meta‐analyses. VTE prophylaxis was associated with a reduced risk of PE (relative risk [RR], 0.45; 95% confidence interval [CI], 0.28–0.72; P=0.0008) or symptomatic VTE (RR, 0.44; 95% CI, 0.28–0.71; P=0.0006) compared to the control without significant heterogeneity. Median incidence (interquartile range) of symptomatic DVT, PE, and fatal PE were 3.2% (0.6–8.1), 0.6% (0.3–2.9), and 0.3% (0.08–1.7), respectively. Previous history of VTE, obesity, left or right ventricular failure, and prolonged bed rest, mechanical ventilation, or use of a central venous catheter were common risk factors for VTE. Bleeding or cardiac tamponade requiring reoperation owing to pharmacological VTE prophylaxis alone, without systemic anticoagulation, was not observed.ConclusionsUnless proven otherwise by adequately powered RCTs, initiating pharmacological VTE prophylaxis as soon as possible after cardiac surgery for patients who have no active bleeding is highly recommended.

The Incidence of Clinical Venous Thromboembolism and Use of Ambulatory Prophylaxis Methods in Bedridden Acutely Ill Medical Outpatients: The ETAPE Study.

Risk of Pregnancy-Associated Venous Thromboembolism in Sickle Cell Trait

To discuss the role of low-molecular-weight heparins (LMWHs) in the prevention of venous thromboembolism (VTE) in medical and orthopedic surgery patients. VTE prophylaxis trials in these practice settings establishing the current use of LMWHs marketed in the US are included. An overview is also provided of VTE incidence, risk factors, and prophylaxis consensus guidelines. Clinical trials, review articles, and meta-analyses for Food and Drug Administration-approved LMWHs were identified from a MEDLINE search (1980-March 2002). Search terms included dalteparin, enoxaparin, internal medicine, low-molecular-weight heparin, orthopedic surgery, risk factors, tinzaparin, and venous thromboembolism. Consensus guidelines are useful as an initial guide to appropriate VTE prophylaxis; however, a review of the primary literature is needed to identify optimal agents, regimens, or interventions. LMWHs have demonstrated sound efficacy in VTE prevention; however, the quantity and quality of literature are not always comparable for the available agents. Enoxaparin has demonstrated efficacy and safety in VTE prevention in medical patients, whereas information is limited or lacking for dalteparin and tinzaparin. Total hip replacement (THR) trials have been conducted with all US-marketed LMWHs and have demonstrated the efficacy and safety of each agent. Trials specifically establishing the efficacy of an LMWH in total knee replacement surgery (TKR) have been published for enoxaparin. One combination THR and TKR trial has been published for tinzaparin. These trial outcomes have positioned the LMWHs as key alternatives to adjusted-dose warfarin for VTE prophylaxis in orthopedic surgery. Inherent differences between LMWHs prevent the extrapolation of clinical outcomes from 1 trial to another.

Venous Thromboembolism in Plastic Surgery: Where Are We Now?

Deep vein thrombosis and pulmonary embolism are collectively called venous thromboembolism (VTE) and are a major cause of morbidity and mortality in the United States and Europe. March is deep vein thrombosis awareness month in the United States, and each year Arteriosclerosis, Thrombosis, and Vascular Biology marks this event with a series of reviews on VTE. This year we have 3 excellent articles on (1) mouse models of venous thrombosis, (2) risk factors for VTE in humans, and (3) the new generation of oral anticoagulants that are available to treat VTE. See accompanying articles on pages 556, 563, and 569 The first review, by Diaz et al1 describes how the use of mouse models has increased our understanding of the mechanisms of initiation, propagation, and resolution of venous clots. The obvious advantage of mice is that we can determine the effect of the loss or mutation of any given gene on thrombosis. Indeed, work with P-selectin knockout mice suggested a role for P-selectin in venous thrombosis that was subsequently confirmed in nonhuman primates. It will be interesting to see whether P-selectin inhibitors will be successfully developed as anticoagulant drugs. Mice have several disadvantages, however, including their small size, their resistance to thrombosis, and the surgical challenges of working with small vessels. Diaz et al1 evaluate 4 inferior vena cava (IVC) thrombosis models. The ferric chloride model induces oxidative damage to the vessel wall that produces an occlusive thrombosis. The advantage of this model is that it is …

British Journal of HaematologyEarly View LETTER TO THE EDITOR A national survey assessing prevention of hospital-associated venous thromboembolism in English Mental Health Trusts A. Purcell, A. Purcell Pharmacy Department, Saint John of God Hospital, Dublin, IrelandSearch for more papers by this authorM. Cheah, M. Cheah Surrey and Borders Partnership, NHS Foundation Trust, London, UKSearch for more papers by this authorJ. Jenkinson, J. Jenkinson Surrey and Borders Partnership, NHS Foundation Trust, London, UKSearch for more papers by this authorJ. Jerrome, J. Jerrome @@ThrombosisUK Thrombosis UK, Maidstone, UKSearch for more papers by this authorA. Mohamed, A. Mohamed Surrey and Borders Partnership, NHS Foundation Trust, London, UKSearch for more papers by this authorB. J. Hunt, Corresponding Author B. J. Hunt [email protected] orcid.org/0000-0002-4709-0774 @@bhwords Thrombosis UK, Maidstone, UK Kings Healthcare Partners, London, UK Correspondence B. J. Hunt, Thrombosis and Haemostasis Centre, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK. Email: [email protected]Search for more papers by this author A. Purcell, A. Purcell Pharmacy Department, Saint John of God Hospital, Dublin, IrelandSearch for more papers by this authorM. Cheah, M. Cheah Surrey and Borders Partnership, NHS Foundation Trust, London, UKSearch for more papers by this authorJ. Jenkinson, J. Jenkinson Surrey and Borders Partnership, NHS Foundation Trust, London, UKSearch for more papers by this authorJ. Jerrome, J. Jerrome @@ThrombosisUK Thrombosis UK, Maidstone, UKSearch for more papers by this authorA. Mohamed, A. Mohamed Surrey and Borders Partnership, NHS Foundation Trust, London, UKSearch for more papers by this authorB. J. Hunt, Corresponding Author B. J. Hunt [email protected] orcid.org/0000-0002-4709-0774 @@bhwords Thrombosis UK, Maidstone, UK Kings Healthcare Partners, London, UK Correspondence B. J. Hunt, Thrombosis and Haemostasis Centre, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK. Email: [email protected]Search for more papers by this author First published: 07 June 2023 https://doi.org/10.1111/bjh.18913Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1 National Institute for Health and Care Excellence. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism NICE guideline [NG89] [Updated August 2019; cited 2022 Dec 12]. Available from: https://www.nice.org.uk/guidance/NG89 2Delluc A, Montavon S, Canceil O, Carpentier M, Nowak E, Mercier B, et al. Incidence of venous thromboembolism in psychiatric units. Thromb Res. 2012; 130(6): e283– 8 [cited 2022 Dec 12]. Available from: 10.1016/j.thromres.2012.10.002 3 Personal Communication. Professor Sebastian Lucas, former professor of pathology. King's College, London. 4 Department of Health UK. Risk assessment for venous thromboembolism. 2010 [cited 2022 Dec 12]. Available from: https://www.nice.org.uk/guidance/ng89/resources/department-of-health-vte-risk-assessment-tool-pdf-4787149213 5Hippisley-Cox J, Coupland C. Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: prospective cohort study. BMJ. 2011; 343:d4656. https://doi.org/10.1136/bmj.d4656 6Barbui C, Conti V, Cipriani A. Antipsychotic drug exposure and risk of venous thromboembolism: a systematic review and meta-analysis of observational studies. Drug Saf. 2014; 37(2): 79– 90. https://doi.org/10.1007/s40264-013-0127-6 7Zhang R, Dong L, Shao F, Tan X, Ying K. Antipsychotics and venous thromboembolism risk: a meta-analysis. Pharmacopsychiatry. 2011; 44(5): 183– 8. https://doi.org/10.1055/s-0031-1280814 8Xuan D, Chen M, Shen S, Cui X. Antipsychotic use and risk of venous thromboembolism: a meta-analysis. Psychiatry Res. 2021; 296:113691. https://doi.org/10.1016/j.psychres.2020.113691 9Liu Y, Xu J, Fang K, Xu Y, Gao J, Zhou C, et al. Current antipsychotic agent use and risk of venous thromboembolism and pulmonary embolism: a systematic review and meta-analysis of observational studies. Ther Adv Psychopharmacol. 2021; 14(11). https://doi.org/10.1177/2045125320982720 10Purcell A, Clarke M, Maidment I. Venous thromboembolism prophylaxis in mental health in-patient services: a qualitative study. Int J Clin Pharm. 2018; 2018(40): 543– 9. https://doi.org/10.1007/s11096-018-0599-7 11Kunutsor S, Seidu S, Khunti K. Depression, antidepressant use, and risk of venous thromboembolism: a systematic review and meta-analysis of published observational evidence. Ann Med. 2018; 50(6): 529– 37. https://doi.org/10.1080/07853890.2018.1500703 12Wang Y, Ye Z, Liu L, Cui X. Antidepressant use and risk of venous thromboembolism: a systematic review and meta-analysis. J Pharm Sci. 2019; 22(1): 57– 71. https://doi.org/10.18433/jpps30129 13Laporte S, Chapelle C, Caillet P, Beyens M-N, Bellet F, Delavenne X. Bleeding risk under antidepressants: a meta-analysis of observational studies. Pharmacol Res. 2017; 118: 19– 32. https://doi.org/10.1016/j.phrs.2016.08.017 14Jiang H-Y, Chen H-Z, Hu X-JE, Yu Z-H, Yang W, Deng M, et al. Use of serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2015; 13(1): 42– 50. e3. https://doi.org/10.1016/j.cgh.2014.06.021 Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Venous thromboembolic disease: An observational study in medical-surgical intensive care unit patients

Recent studies have shown conflicting results regarding the risk of venous thromboembolism (VTE) in cirrhotics despite the often-associated coagulopathy. Our aim was to determine burden and risk factors for VTE in cirrhotics from a national sample. Using data from the Nationwide Inpatient Sample 2005, we identified cirrhosis-related hospitalizations using appropriate discharge codes. Our outcomes of interest were deep venous thrombosis (DVT) or pulmonary embolism (PE). Cirrhotics without VTE formed the controls. Multivariate regression models were used to identify factors independently associated with VTE and the impact of VTE diagnosis on in-hospital outcomes. There were 449,798 hospitalizations for cirrhosis in 2005 of which 8,231 were for VTE (1.8%). This rate was lower than the rate for chronic hepatitis C (2.4%) or all-cause hospitalizations (3.7%). Patients with VTE were older than controls and had greater co-morbidity and were more likely to have malnutrition, parenteral nutrition, prolonged mechanical ventilation, and central venous line (CVL) placement. Complications of cirrhosis including hepatic encephalopathy, variceal bleeding, ascites, and coagulopathy were less frequent in those with VTE than controls. On multivariate regression, greater co-morbidity, black race, malnutrition, and CVL placement were independently associated with VTE. Neither DVT nor PE was associated with greater in-hospital mortality. DVT, but not PE, was associated with a 52% increase in LOS and hospitalization charges. Despite the often-associated coagulopathy, VTE contributes to a significant burden in patients with cirrhosis. Efforts directed at VTE prevention in this cohort, especially high-risk patients, should be actively pursued.

Objective: To determine the risk profile of venous thromboembolism (VTE) and evaluate VTE prophylaxis implementation of the hospitalized cancer patients in the DissolVE 2 study. Methods: The data of hospitalized cancer patients in the DissolVE 2 study were analyzed. The risk distribution of VTE, preventive measures and in-hospital VTE events of hospitalized patients with tumors were described by percentage and 95% confident interval (CI). Results: A total of 1 535 cancer patients were included. According to the Padua score, 826 (53.8%) patients were at low risk of VTE, while 709 (46.2%) patients were at high VTE risk. VTE events occurred in 4 low-risk patients (0.5%; 95%CI: 0.1%, 1.2%) and 5 high-risk patients (0.7%; 95%CI: 0.2%, 1.6%). The overall incidence was 0.6% (9/1 535, 95%CI: 0.3%, 1.1%). Among patients with high VTE risk, 666 (93.9%) did not receive any VTE prophylaxis, and only 11 (1.6%) patients received appropriate VTE prophylaxis. Among patients who received VTE prevention, no VTE event was observed. Conclusions: Nearly half of the hospitalized cancer patients are at high risk of VTE, but most of them don't receive VTE prophylaxis. The results reflect the insufficient management of VTE risk for hospitalized cancer patients in China, and improvement of awareness and practice of VTE prophylaxis is urgently needed.

AimsThe aims of this study were to compare the efficacy of two agents,aspirin and warfarin, for the prevention of venous thromboembolism(VTE) after simultaneous bilateral total knee arthroplasty (SBTKA),and to elucidate the risk of VTE conferred by this procedure comparedwith unilateral TKA (UTKA).Patients and MethodsA retrospective, multi-institutional study was conducted on 18951 patients, 3685 who underwent SBTKA and 15 266 who underwentUTKA, using aspirin or warfarin as VTE prophylaxis. Each patientwas assigned an individualised baseline VTE risk score based ona system using the Nationwide Inpatient Sample. Symptomatic VTE,including pulmonary embolism (PE) and deep vein thrombosis (DVT),were identified in the first 90 days post-operatively. Statisticalanalyses were performed with logistic regression accounting forbaseline VTE risk.ResultsThe adjusted incidence of PE following SBTKA was 1.0% (95% confidenceinterval (CI) 0.86 to 1.2) with aspirin and 2.2% (95% CI 2.0 to2.4) with warfarin. Similarly, the adjusted incidence of VTE followingSBTKA was 1.6% (95% CI 1.1 to 2.3) with aspirin and 2.5% (95% CI1.9 to 3.3) with warfarin. The risk of PE and VTE were reduced by66% (odds ratio (OR) 0.44, 95% CI 0.25 to 0.78) and 38% (OR 0.62,95% CI 0.38 to 1.0), respectively, using aspirin. In addition, the riskof PE was 204% higher for patients undergoing SBTKA relative tothose undergoing UTKA. For each ten-point increase in baseline VTErisk, the risk of PE increased by 25.5% for patients undergoingSBTKA compared with 10.5% for those undergoing UTKA. Patients witha history of myocardial infarction or peripheral vascular disease hadthe greatest increase in risk from undergoing SBTKA instead of UTKA.ConclusionAspirin is more effective than warfarin for the prevention ofVTE following SBTKA, and serves as the more appropriate agent forVTE prophylaxis for patients in all risk categories. Furthermore,patients undergoing SBTKA are at a substantially increased riskof VTE, even more so for those with significant underlying riskfactors. Patients should be informed about the risks associatedwith undergoing SBTKA.Cite this article: Bone Joint J 2018;100-B(1Supple A):68–75.

Utilization of Venous Thromboembolism Prophylaxis in a Medical-Surgical ICU

Venous thromboembolism (VTE) has been traditionally considered a transient acute disorder requiring a limited duration of anticoagulant therapy. Patients who suffer deep vein thrombosis (DVT) or pulmonary embolism (PE) following major surgery, major trauma, or periods of immobility are generally treated with anticoagulation for 3–6 months. After completion of anticoagulation for the initial event, the risk of VTE recurrence is believed to return to that of the general population. However, epidemiological studies suggest that VTE may be better characterized as a chronic disorder with periodic relapses. While patients who suffer unprovoked (idiopathic) VTE bear the highest risk of recurrent events, exceeding 50% over 10 years if not treated with extended duration anticoagulation, those who suffer VTE in the setting of identifiable provoking factors have an enduring risk of recurrence that exceeds 20% over 10 years. 1 Randomized controlled trials of extended duration anticoagulation for prevention of recurrent unprovoked VTE have demonstrated that the rate of recurrence increases abruptly if anticoagulation is discontinued. 2 An analysis of the Danish National Registry of Patients demonstrated that patients with VTE have increased mortality over 30 years of follow-up and that recurrent PE is an important cause of death throughout this period. 3 The efficacy of extended duration anticoagulation for prevention of recurrent events after an initial unprovoked DVT or PE further supports the classification of VTE as a chronic relapsing disease. Prolonged anticoagulation with a low- (international normalized ratio (INR) target 1.5–2.0) 4 or conventional-intensity (INR target 2.0–3.0) 5 or a non-vitamin K-dependent oral anticoagulant such as rivaroxaban, 6 dabigatran, 2 or apixaban 7 provides a 60–90% reduction in recurrent events in patients who suffer an initial unprovoked VTE. Evidence-based practice guidelines recognize the increased risk of recurrence among patients with idiopathic VTE and recommend extended duration anticoagulation in those with a low bleeding risk. Virchow’s Triad of stasis, hypercoagulability, and endothelial dysfunction and injury does not fully explain the increased risk of recurrent VTE and the need for extended duration anticoagulation. Immobility resulting in stasis is only a transient risk factor in the majority of patients with VTE. Although frequently sought as an explanation for VTE, thrombophilia is detected in only a minority of patients. 8 Furthermore, common thrombophilias such as the factor V Leiden and prothrombin gene mutations do not appear to increase the risk of recurrence. 8 Endothelial dysfunction and injury may play an important role in a subset of patients with VTE, but the underlying mechanism leading to recurrence remains unclear. Advances in our understanding of the pathophysiology of atherothrombosis may shed light on critical mechanisms for VTE recurrence. Traditionally, the burden of recurrent atherothrombotic events has been largely ascribed to dyslipidemia. However, even with intensive lipid-lowering therapy for secondary prevention, a significant burden of recurrent atherothrombotic events remains. A growing body of literature suggests that cardiovascular inflammation is a key pathophysiologic factor in recurrent atherothrombotic events. 9,10 Traditionally considered distinct and unrelated disorders, atherothrombosis and VTE are linked both epidemiologically and pathophysiologically. In fact, a reciprocal relationship exists: patients with VTE have an increased risk of myocardial infarction and stroke, and vice versa. Proven cardiovascular risk factors such as obesity, tobacco use, diabetes, stress, and diet increase the risk of atherothrombotic events and VTE. These particular risk factors share a common pathophysiological mechanism of promoting cardiovascular inflammation. In epidemiologic studies, systemic inflammation has been closely associated with an increased risk of VTE. The increased frequency of DVT and PE in patients with chronic inflammatory disorders such as inflammatory bowel disease and systemic vasculitis highlights the role of inflammation in VTE. Furthermore, increased levels of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of VTE. In an analysis of 10,505 participants in