Venous Thromboembolism In People Research Articles

Venous thrombosis and obesity: from clinical needs to therapeutic challenges.

Weight bias and stigma have limited the awareness of the systemic consequences related to obesity. As the narrative evolves, obesity is emerging as a driver and enhancer of many pathological conditions. Among these, the risk of venous thromboembolism (VTE) is a critical concern linked to obesity, ranking as the third most common cardiovascular condition. Obesity is recognized as a multifactorial risk factor for VTE, influenced by genetic, demographic, behavioral, and socio-economic conditions. Despite established links, the exact incidence of obesity related VTE in the general population remains largely unknown. The complexity of distinguishing between provoked and unprovoked VTE, coupled with gaps in obesity definition and assessment still complicates a tailored risk assessment of VTE risk. Obesity reactivity, hypercoagulability, and endothelial dysfunction are driven by the so-called 'adiposopathy'. This state of chronic inflammation and metabolic disturbance amplifies thrombin generation and alters endothelial function, promoting a pro-thrombotic environment. Additionally, the inflammation-induced clot formation-also referred to as 'immunothrombosis' further exacerbates VTE risk in people living with obesity. Furthermore, current evidence highlights significant gaps in the management of obesity related VTE, particularly concerning prophylaxis and treatment efficacy of anticoagulants in people living with obesity. This review underscores the need for tailored therapeutic approaches and well-designed clinical trials to address the unique challenges posed by obesity in VTE prevention and management. Advanced research and innovative strategies are imperative to improve outcomes and reduce the burden of VTE in people living with obesity.

Pharmacological interventions for preventing venous thromboembolism in people undergoing bariatric surgery.

Pharmacological interventions for preventing venous thromboembolism in people undergoing bariatric surgery.

Blood thinners for the initial treatment of blood clots in people with cancer

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Lara A Kahale, Charbel F Matar, Maram B Hakoum, Ibrahim G Tsolakian, Victor ED Yosuico, Irene Terrenato, Francesca Sperati, Maddalena Barba, Holger Schnemann, Elie A Akl. Anticoagulation for the initial treatment of venous thromboembolism in people with cancer. Cochrane Database of Systematic Reviews 2021, Issue 12. Art. No.: CD006649. DOI:10.1002/14651858.CD006649.pub8

Can combined intermittent pneumatic leg compression and pharmacological prophylaxis prevent venous thromboembolism in people undergoing surgery?

Can combined intermittent pneumatic leg compression and pharmacological prophylaxis prevent venous thromboembolism in people undergoing surgery?

Elevated Risk of Venous Thromboembolism in People Living with HIV.

Human immunodeficiency virus (HIV) has been generally considered as a highly adaptive and rapidly evolving virus. It still constitutes a major public health problem all over the world despite an effective outcome in the prevention and reversal of the development and prognosis by using antiretroviral therapy. The salient question lies in the more frequent emergence of a series of comorbidities along with the prolongation of the life, which deeply affects the survival in such group. Venous thromboembolism (VTE) has been recognized to be the third most common cardiovascular condition within people living with HIV (PWH). In terms of its mechanism of action, the occurrence of VTE is quite multifactorial and complex in HIV. Prior exploration concerning the etiology of VTE in PWH identifies general, disease-specific, and miscellaneous factors for explaining its occurrence and development. VTE has constituted an important role in PWH and may increase its all-cause mortality. Therefore, it is quite necessary to understand VTE from the following aspects of epidemiology, pathophysiology, molecular mechanisms, and therapeutic interventions so as to balance the risks and benefits of anticoagulation and optimize corresponding treatment.

Anticoagulation for the initial treatment of venous thromboembolism in people with cancer.

Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer. We performed a comprehensive search in the following major databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid). We also handsearched conference proceedings, checked references of included studies, and searched for ongoing studies. This update of the systematic review is based on the findings of a literature search conducted on 14 August 2021. Randomised controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE. Using a standardised form, we extracted data - in duplicate - on study design, participants, interventions, outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, symptomatic VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach. Of 11,484 identified citations, 3073 were unique citations and 15 RCTs fulfilled the eligibility criteria, none of which were identified in the latest search. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH; one compared fondaparinux with UFH and LMWH; and one compared dalteparin with tinzaparin, two different types of low molecular weight heparin. The meta-analyses showed that LMWH may reduce mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; low certainty evidence) and may reduce VTE recurrence slightly (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; low certainty evidence). There were no data available for bleeding outcomes, postphlebitic syndrome, quality of life, or thrombocytopenia. The study comparing fondaparinux with heparin (UFH or LMWH) found that fondaparinux may increase mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; low certainty evidence), may result in little to no difference in recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; low certainty evidence), may result in little to no difference in major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; low certainty evidence), and probably increases minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence). There were no data available for postphlebitic syndrome, quality of life, or thrombocytopenia. The study comparing dalteparin with tinzaparin found that dalteparin may reduce mortality slightly (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), may reduce recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), may increase major bleeding slightly (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), and may reduce minor bleeding slightly (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence). There were no data available for postphlebitic syndrome, quality of life, or thrombocytopenia. Low molecular weight heparin (LMWH) is probably superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.

Physician and Patient Beliefs and Preferences in Pulmonary Embolism and Deep Vein Thrombosis Testing in People with Cancer

IntroductionIt is unclear whether evidence-based diagnostic protocols are followed when cancer patients are tested for venous thromboembolism (VTE). Evidence-based protocols reduce unnecessary diagnostic imaging, offer a patient-centered approach, and have the potential to standardize practice across medical specialties and settings. However, anecdote suggests that specialists who test people with cancer for VTE may prefer diagnostic imaging over clinical probability scoring and D-dimer testing. The aim of this study was to identify physician and patient knowledge, beliefs, values and preferences for VTE testing in cancer. This study was part of a program of research to set International Society of Thrombosis and Haemostasis standards for VTE testing in people with cancer.MethodsThis was an international qualitative interview study following COREQ guidelines. Semi-structured interviews with physicians and cancer patients were conducted via Zoom. We used purposive sampling to ensure inclusion of physicians from all specialties who test people with cancer for VTE, practicing across all continents. We invited people treated for cancer who had and did not have experience of VTE testing. We used grounded theory to create a conceptual framework which explains physician and patient values and preferences for VTE testing. Transcripts were coded by three researchers independently, who met to discuss their findings and agree on common codes. Researchers were a Thrombosis physician and two undergraduate students who ensured reflexivity was incorporated into their analysis.ResultsA total of 32 physicians and 6 cancer patients were invited to interview. Of those invited, 23 physicians and 6 patients across 6 continents completed an interview. Interviews lasted between 21 and 86 minutes. Our derived conceptual model can be seen in the attached Figure. Physicians reported a low threshold to test for VTE in people with cancer compared to those without cancer, because VTE was considered a fatal disease and highly prevalent in this patient population. Imaging was generally the only test used for VTE testing in cancer patients. Many participants relied on their Gestalt estimation of VTE probability when deciding whether to order imaging for pulmonary embolism or deep vein thrombosis. Most thought that low Wells score in combination with a negative D-dimer was not sufficiently sensitive to exclude VTE and anticipated the Wells score and D-dimer to be elevated. The Wells scores had poor face validity because they do not include cancer-specific variables and participants hoped to see a more nuanced formal score for VTE testing in cancer patients. Participants believed that their colleagues would support their diagnostic approach.Patients reported they were used to having tests and CT scans. Patients felt it was important for their physicians to prioritize testing for VTE. Patients had full trust and confidence in their physicians' testing decisions, particularly in decisions made by their oncologists.ConclusionPhysicians have a low threshold to test people with cancer for VTE and tend not to use clinical probability assessment and D-dimer. Patients are comfortable having diagnostic imaging, feel VTE testing is important and have full trust in their physicians. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Venous Thromboembolism and Risk of Cancer in Patients with Dementia: A Danish Population-Based Cohort Study.

Background:Venous thromboembolism (VTE) may be the first manifestation of occult cancer. Dementia has been linked to reduced cancer risk.Objective:We examined the risk of cancer following VTE in people with dementia in comparison to the risk in the general population.Methods:We conducted a population-based Danish registry-based cohort study following patients with a first-time VTE and a previous or concurrent diagnosis of dementia during the period 1 April 1996 –31 December 2017. We followed the study participants from date of VTE until diagnosis of cancer, death, emigration, or end of study period, whichever came first. The absolute risk of cancer within one year after VTE was computed, treating death as a competing risk. We calculated gender, age, and calendar-period standardized incidence ratios (SIRs) of cancer based on national cancer rates.Results:We followed 3,552 people with dementia and VTE for a median of 1.3 years. Within the first year after VTE, they had a 90% increased risk of cancer in comparison with the general population [SIR: 1.9 (95% confidence interval: 1.6–2.4)]. During subsequent follow-up years, the SIR fell to 0.7 (95% confidence interval: 0.5–0.8). Findings for Alzheimer’s disease and VTE were similar.Conclusion:People with dementia have an increased risk of a cancer diagnosis during the first year following VTE, perhaps related to increased surveillance, and a lower risk thereafter. Overall risk is similar to that of the general population.

Risk of recurrent venous thromboembolism in patients with autoimmune diseases: data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry.

SummaryAutoimmune disease is a risk factor for first incident venous thromboembolism (VTE). However, data on the risk of recurrent VTE in people with autoimmune disease is sparse. We explored the risk of recurrent VTE using the RIETE registry, comparing people with autoimmune disease (n = 1305) to those without (n = 50608). Overall rates were 6.5 and 5.1 recurrent VTE/100 years for patients with autoimmune disease vs controls, respectively. After adjustment for sex and unprovoked/provoked VTE yielded an adjusted hazard ratio of 1.29 (95%CI 1.03‐1.62). The analysis was limited by short median follow up time (161 days overall), precluding definitive conclusions on recurrent VTE risks.

Effect of type 1 diabetes and type 2 diabetes on the risk of venous thromboembolism.

AimsWhether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2 diabetes for VTE risk.MethodsRetrospective cohort study of the Royal College of General Practitioners Research and Surveillance Centre, comprising over 530 primary care practices. We determined whether type 1 diabetes and/or type 2 diabetes are independent risk factors for VTE. The index date was 1 January 2009, individuals were followed to 31 December 2018, or censoring. Cox proportional hazard regression analysis was used to investigate the risk of VTE in people with type 1 diabetes and type 2 diabetes relative to no diabetes. The primary outcome was occurrence of VTE. The model was adjusted for potential confounders for VTE.ResultsThere were 7086 people with type 1 diabetes and 95,566 with type 2 diabetes, diagnosed before 1 January 2009. The non‐diabetes group consisted of 1,407,699 people. In the unadjusted analysis, there was no increased risk of VTE with type 1 diabetes (HR 1.00, 95% CI 0.76–1.33) but there was for type 2 diabetes (HR 2.70, 95% CI 2.57–2.84). In the fully adjusted model, VTE risk was increased in type 1 diabetes (HR 1.46, 95% CI 1.11–1.92), but not with type 2 diabetes (HR 1.06, 95% CI 0.98–1.14).ConclusionsType 1 diabetes was associated with a greater risk for VTE while type 2 diabetes was not. Further work is needed to determine the reason(s) for this.

Primary prophylaxis for venous thromboembolism in people undergoing major amputation of the lower extremity.

People undergoing major amputation of the lower limb are at increased risk of venous thromboembolism (VTE). Risk factors for VTE in amputees include advanced age, sedentary lifestyle, longstanding arterial disease and an identifiable hypercoagulable condition. Evidence suggests that pharmacological prophylaxis (e.g. heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, antiplatelets) is effective in preventing deep vein thrombosis (DVT), but is associated with an increased risk of bleeding. Mechanical prophylaxis (e.g. antiembolism stockings, intermittent pneumatic compression and foot impulse devices), on the other hand, is non-invasive and has minimal side effects. However, mechanical prophylaxis is not always appropriate for people with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis for people undergoing major amputation and whether this is one treatment alone or in combination with another. This is an update of the review first published in 2013. To determine the effectiveness of thromboprophylaxis in preventing VTE in people undergoing major amputation of the lower extremity. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 5 November 2019. We planned to undertake reference checking of identified trials to identify additional studies. We did not apply any language restrictions. We included randomised controlled trials and quasi-randomised controlled trials which allocated people undergoing a major unilateral or bilateral amputation (e.g. hip disarticulation, transfemoral, knee disarticulation and transtibial) of the lower extremity to different types or regimens of thromboprophylaxis (including pharmacological or mechanical prophylaxis) or placebo. Two review authors independently selected studies, extracted data and assessed risk of bias. We resolved any disagreements by discussion. Outcomes of interest were VTE (DVT and pulmonary embolism (PE)), mortality, adverse events and bleeding. We used GRADE criteria to assess the certainty of the evidence. The two included studies compared different treatments, so we could not pool the data in a meta-analysis. We did not identify any eligible new studies for this update. Two studies with a combined total of 288 participants met the inclusion criteria for this review. Unfractionated heparin compared to low molecular weight heparin One study compared unfractionated heparin with low molecular weight heparin and found no evidence of a difference between the treatments in the prevention of DVT (odds ratio (OR) 1.23, 95% confidence interval (CI) 0.28 to 5.35; 75 participants; very low-certainty evidence). No bleeding events occurred in either group. Deaths and adverse events were not reported. This study was open-label and therefore at a high risk of performance bias. Additionally, the study did not report the method of randomisation, so the risk of selection bias was unclear. Heparin compared to placebo In the second study, there was no evidence of a benefit from heparin use in preventing PE when compared to placebo (OR 0.84, 95% CI 0.35 to 2.01; 134 participants; low-certainty evidence). Similarly, no evidence of improvement was detected when the level of amputation was considered, with a similar incidence of PE between the two treatment groups: above knee amputation (OR 0.79, 95% CI 0.31 to 1.97; 94 participants; low-certainty evidence); and below knee amputation (OR 1.53, 95% CI 0.09 to 26.43; 40 participants; low-certainty evidence). Ten participants died during the study; five underwent a post-mortem and three were found to have had a recent PE, all of whom had been on placebo (low-certainty evidence). Bleeding events were reported in less than 10% of participants in both treatment groups, but the study did not present specific data (low-certainty evidence). There were no reports of other adverse events. This study did not report the methods used to conceal allocation of treatment, so it was unclear whether selection bias occurred. However, this study appeared to be free from all other sources of bias. No study looked at mechanical prophylaxis. We did not identify any eligible new studies for this update. As we only included two studies in this review, each comparing different interventions, there is insufficient evidence to make any conclusions regarding the most effective thromboprophylaxis regimen in people undergoing lower limb amputation. Further large-scale studies of good quality are required.

Global epidemiology of venous thromboembolism in people with active tuberculosis: a systematic review and meta-analysis.

Despite the wide range of studies supporting an association between exposure to active tuberculosis and risk of venous thromboembolism (VTE), the current systematic review and meta-analysis is the first study assessing the global epidemiology of VTE in patients having active tuberculosis. In this systematic review and meta-analysis, EMBASE, Medline, and Web of Science were searched to identify observational studies, published until December 15, 2019, and reporting on venous thromboembolism in patients with active tuberculosis. No language restriction was applied. Studies were synthetized using a random-effect model. This review is registered with PROSPERO, CRD42019130347. We included 9 studies with an overall total of 16,190 patients with active tuberculosis. The prevalence of VTE was 3.5% (95% CI 2.2-5.2) in patients with active tuberculosis. Furthermore, we found a prevalence of pulmonary embolism (PE) at 5.8% (95% CI 2.2-10.7) and for deep vein thrombosis (DVT) at 1.3% (95% CI 0.8-2.0) in patients with active tuberculosis. Patients with active tuberculosis had a higher risk for VTE (OR 2.90; 95% CI 2.30-3.67), DVT (OR 1.56; 95% CI 1.14-2.14), and PE (OR 3.58; 95% CI 2.54-5.05). This study suggests that VTE is not rare among patients with active TB. Cost-effective preventive strategies and interventions to curb this dreadful burden of VTE among people with active TB are needed.

Pharmacological thromboprophylaxis to prevent venous thromboembolism in patients with temporary lower limb immobilization after injury: systematic review and network meta‐analysis

BackgroundThromboprophylaxis has the potential to reduce venous thromboembolism (VTE) following lower limb immobilization resulting from injury. ObjectivesWe aimed to estimate the effectiveness of thromboprophylaxis, compare different agents, and identify any factors associated with effectiveness. MethodsWe undertook a systematic review and network meta‐analysis (NMA) of randomized trials reporting VTE or bleeding outcomes that compared thromboprophylactic agents with each other or to no pharmacological prophylaxis, for this indication. An NMA was undertaken for each outcome or agent used, and a series of study‐level network meta‐regressions examined whether population characteristics, type of injury, treatment of injury, or duration of thromboprophylaxis were associated with treatment effect. ResultsData from 6857 participants across 13 randomized trials showed that, compared with no treatment, low molecular weight heparin (LMWH) reduced the risk of any VTE (odds ratio [OR]: 0.52; 95% credible interval [CrI]: 0.37‐0.71), clinically detected deep vein thrombosis (DVT) (OR: 0.39; 95% CrI: 0.12‐0.94) and pulmonary embolism (PE) (OR: 0.16; 95% CrI: 0.01‐0.74), whereas fondaparinux reduced the risk of any VTE (OR: 0.13; 95% CrI: 0.05‐0.30) and clinically detected DVT (OR: 0.10; 95% CrI: 0.01‐0.86), with inconclusive results for PE (OR: 0.40; 95% CrI: 0.01‐7.53). ConclusionsThromboprophylaxis with either fondaparinux or LMWH appears to reduce the odds of both asymptomatic and clinically detected VTE in people with temporary lower limb immobilization following an injury. Treatment effects vary by outcome and are not always conclusive. We were unable to identify any treatment effect modifiers other than thromboprophylactic agent used.

Epidemiology of venous thromboembolism in people with active tuberculosis: a systematic review and meta-analysis protocol

IntroductionIn recent years, a hypothesis has been raised that people with tuberculosis are at risk for developing venous thromboembolism (VTE). However, much remains to be understood about the interplay between...

Comparison of Activated Protein C Resistance With Factor V Leiden Testing by Molecular Assay

Abstract Factor V Leiden (FVL) is a variant form of coagulation factor V that is the most common inherited risk factor for venous thromboembolism in people of European ancestry. FVL is associated with the missense mutation, p.R506Q, which encodes a FV protein resistant to cleavage by activated protein C (APC). Laboratory testing for FVL includes both phenotypic assays that assess APC resistance (APCR) and molecular assays that evaluate FVL genotype (FVLM) directly. Although APCR results are typically highly concordant with FVL genotype, discrepancies are known to occur and may result in inference of an incorrect FV genotype if only APCR testing is used. The objective of this study was to compare the results of these two testing methodologies and to identify potential explanations for discrepancies in results. Data were obtained by searching the electronic medical record of a large academic hospital for patients who underwent both APCR and FVLM testing from 2013 to 2018. APCR was evaluated using the ratio between two dilute Russell Viper Venom Time (DRVVT) tests, one preincubated with a protein C activator derived from A contortrix contortrix venom and the other with vehicle; the validated normal APCR ratio is ≥1.7. FVLM was performed by invader analysis utilizing fluorescence resonance energy transfer (FRET). In total, 424 patients underwent testing with both assays. Of 21 patients who had APCR assay clot times that exceeded the measurement range, all were FVLM negative, and 15 were anticoagulated during APCR testing. Of the 403 patients with reportable results for both tests, 385 (95.5%) patients had normal APCR and were FVLM negative. Of the 18 (4.5%) patients with discrepant results, 15 (3.7%) had an abnormally low APCR but were FVLM negative, and 3 (0.8%) had a normal APCR but were FVLM heterozygous. Among the 15 FVLM-negative patients with abnormal APCR <1.7, 11 (73.3%) were on warfarin with/out enoxaparin and had low protein S activity and/or low protein C activity. Of the 3 FVLM heterozygous patients with normal APCR, 1 was on apixaban. Our results demonstrated a high concordance between APCR phenotype and FVLM genotype. The concordance of APCR and FVLM may be limited in patients with low protein S or low protein C activity and those on a range of anticoagulant therapy.

Bemiparin as a long-term treatment for venous thrombosis in cancer patients: the ELEBAMA study.

Low-molecular-weight heparin (LMWH) is the standard treatment for cancer-associated venous thromboembolism (VTE). There have been no specific studies evaluating bemiparin for VTE in people with cancer. The aim of this study is to evaluate the effects of bemiparin for long-term treatment of VTE in routine clinical practice. Prospective observational study. Consecutive patients with active cancer and VTE, under treatment with bemiparin for at least 6 months, were recruited. We included 89 patients. The 6- and 9-month cumulative VTE recurrence rates were 2.4% and 5.9%, respectively. The 6-month cumulative rate of major bleeding was 1.3%, and of clinically relevant non-major bleeding, 8%. The incidence of events in this study is lower than that reported in randomized trials. Bemiparin is effective and safe for the long-term treatment of cancer-associated VTE in routine clinical practice.

Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer.

Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer.

Anticoagulation for the initial treatment of venous thromboembolism in people with cancer.

Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer. A comprehensive search included a major electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (2018, Issue 1), MEDLINE (via Ovid) and Embase (via Ovid); handsearching of conference proceedings; checking of references of included studies; use of the 'related citation' feature in PubMed; and a search for ongoing studies. This update of the systematic review was based on the findings of a literature search conducted on 14 January 2018. Randomized controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE. Using a standardized form, we extracted data in duplicate on study design, participants, interventions outcomes of interest, and risk of bias. Outcomes of interested included all-cause mortality, symptomatic VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach. Of 15440 identified citations, 7387 unique citations, 15 RCTs fulfilled the eligibility criteria. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH enrolling 1025 participants, one compared fondaparinux with UFH and LMWH enrolling 477 participants, and one compared dalteparin with tinzaparin enrolling 113 participants. The meta-analysis of mortality at three months included 418 participants from five studies and that of recurrent VTE included 422 participants from 3 studies. The findings showed that LMWH likely decreases mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; moderate certainty evidence), but did not rule out a clinically significant increase or decrease in VTE recurrence (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; moderate certainty evidence).The study comparing fondaparinux with heparin (UFH or LMWH) did not exclude a beneficial or detrimental effect of fondaparinux on mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; moderate certainty evidence), recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; moderate certainty evidence), major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; moderate certainty evidence), or minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence)The study comparing dalteparin with tinzaparin did not exclude a beneficial or detrimental effect of dalteparin on mortality (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), major bleeding (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), or minor bleeding (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence). LMWH is possibly superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.

Can combined intermittent pneumatic leg compression and pharmacological prophylaxis prevent venous thromboembolism in people undergoing surgery?

Can combined intermittent pneumatic leg compression and pharmacological prophylaxis prevent venous thromboembolism in people undergoing surgery?

Risk of venous thromboembolism in people with lung cancer: a cohort study using linked UK healthcare data.

Background:Venous thromboembolism (VTE) is a potentially preventable cause of death in people with lung cancer. Identification of those most at risk and high-risk periods may provide the opportunity for better targeted intervention.Methods:We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics and Cancer Registry data. Our cohort comprises 10 598 people with lung cancer diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, tumour and treatment-related factors (time-varying effects of chemotherapy and surgery) independently affected VTE risk. We also determined the effect of a VTE diagnosis on the survival of people with lung cancer.Results:People with lung cancer had an overall VTE incidence of 39.2 per 1000 person-years (95% confidence interval (CI), 35.4–43.5), though rates varied depending on the patient group and treatment course. Independent factors associated with increased VTE risk were metastatic disease (hazard ratio (HR)=1.9, CI 1.2–3.0 vs local disease); adenocarcinoma subtype (HR=2.0, CI 1.5–2.7, vs squamous cell; chemotherapy administration (HR=2.1, CI 1.4–3.0 vs outside chemotherapy courses); and diagnosis via emergency hospital admission (HR=1.7, CI 1.2–2.3 vs other routes to diagnosis). Patients with VTE had an approximately 50% higher risk of mortality than those without VTE.Conclusions:People with lung cancer have especially high risk of VTE if they have advanced disease, adenocarcinoma or are undergoing chemotherapy. The presence of VTE is an independent risk factor for death.