Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study

Combined oral contraceptives,oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women.The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47).Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users

Update on Extended Treatment for Venous Thromboembolism

The importance of assessing the probability of venous thromboembolism recurrence, a condition that includes deep vein thrombosis and pulmonary embolism, lies in the fact that it is the most important factor in deciding the duration of anticoagulant treatment. Risk of recurrence depends mostly on the presence of a risk factor for developing venous thromboembolism, with patients with unprovoked events being at the higher risk of recurrence. The risk of recurrence needs to be balanced with the risk of bleeding and the potential severity of these thrombotic and hemorrhagic events. In patients with an unprovoked venous thromboembolism who complete treatment for the acute (first 10 days) and post-acute phase of the disease (from day 10 to 3-6 months), decision has to be made regarding prolonged antithrombotic therapy to prevent recurrences. The main goal of extended treatment is preventing recurrences with a safe profile in terms of bleeding risk. Many therapeutic options are now available for these patients, including antiplatelet therapy with aspirin or direct oral anticoagulants. Moreover, apixaban and rivaroxaban at prophylactic doses have demonstrated efficacy in preventing recurrences with a low risk of bleeding

Cancer patients’ experiences of living with venous thromboembolism: A systematic review and qualitative thematic synthesis

Background: Cancer-Associated thrombosis is common. Recommended treatment is daily injected low-molecular-weight heparin for 6months. Most studies focus on prophylaxis and treatment; few have explored patients’ experience. Aims To identify and synthesise the available literature concerning patients’ experience of cancer associated thrombosis. Design Systematic literature review and qualitative thematic synthesis. MethodsMEDLINE, Embase, CINAHL, PsychINFO (until 10/2016; limited to English) were searched. Eligible papers were qualitative studies of adult patients’ experience of cancer-associated thrombosis. Two researchers screened titles/abstracts/papers against inclusion criteria with recourse to a third for disagreements. Critical Appraisal Skills Programme qualitative checklist tool was used for quality appraisal. Results1397 articles were identified. Five qualitative studies (total n=92; age range 32 to 84 years) met the inclusion criteria. Participants had various cancer types. Most had advanced disease and were receiving palliative care. Four major themes emerged from the data: knowledge deficit (patients and clinicians); effects of cancer associated thrombosis (physical and psychological); effects of anticoagulation; coping strategies. ConclusionThe cancer journey is difficult in itself, but thrombosis was an additional, frightening and unexpected burden. Although the association between cancer and thromboembolism is well known, cancer patients are not educated routinely about the risk or warning symptoms/signs of thromboembolism which may otherwise be misattributed to the cancer by patient and clinician alike. This systematic review highlights the impact of cancer-associated thrombosis on the lives of cancer patients, and calls for education for patients and clinicians to be part of routine care, and further work to address this patient priority

Extended thromboprophylaxis with betrixaban in acutely ill medical patients

BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.)

Cardioverting acute atrial fibrillation and the risk of thromboembolism: not all patients are created equal

Current guidelines support the well-established clinical practice that patients who present with atrial fibrillation (AF) of less than 48 hours duration should be considered for cardioversion, even in the absence of pre-existing anticoagulation. However, with increasing evidence that short runs of AF confer significant risk of stroke, on what evidence is this 48-hour rule based and is it time to adopt a new approach? We review existing evidence and suggest a novel approach to risk stratification in this setting. Overall, the risk of thromboembolism associated with acute cardioversion of patients with AF that is estimated to be of <48 hours duration is low. However, this risk varies widely depending on patient characteristics. From existing evidence, we show that using the CHA2DS2-VASc score may allow better selection of appropriate patients in order to prevent exposing specific patient groups to an unacceptably high risk of a potentially devastating complication

Risk marker associations with venous thrombotic events: a cross-sectional analysis.

ObjectiveTo examine the interrelations among, and risk marker associations for, superficial and deep venous events-superficial venous thrombosis (SVT), deep venous thrombosis (DVT) and pulmonary embolism (PE).DesignCross-sectional analysis.SettingSan Diego, California, USA.Participants2404 men and women aged 40-79 years from four ethnic groups: non-Hispanic White, Hispanic, African-American and Asian. The study sample was drawn from current and former staff and employees of the University of California, San Diego and their spouses/significant others.Outcome measuresSuperficial and deep venous events, specifically SVT, DVT, PE and combined deep venous events (DVE) comprising DVT and PE.ResultsSignificant correlates on multivariable analysis were, for SVT: female sex, ethnicity (African-American=protective), lower educational attainment, immobility and family history of varicose veins. For DVT and DVE, significant correlates included: heavy smoking, immobility and family history of DVEs (borderline for DVE). For PE, significant predictors included immobility and, in contrast to DVT, blood pressure (BP, systolic or diastolic). In women, oestrogen use duration for hormone replacement therapy, in all and among oestrogen users, predicted PE and DVE, respectively.ConclusionsThese findings fortify evidence for known risk correlates/predictors for venous disease, such as family history, hormone use and immobility. New risk associations are shown. Striking among these is an association of PE, but not DVT, to elevated BP: we conjecture PE may serve as cause rather than consequence. Future studies should evaluate the temporal direction of this association. Oxidative stress and cell energy compromise are proposed to explain and predict many risk factors, operating through cell-death mediated triggering of coagulation activation

Simple measures can improve care in our hospitals : an audit of venous thromboembolism practice

Abstract: Venous thromboembolism (VTE) is a serious but preventable complication of hospitalisation. Doctors still sometimes fail to adhere to them, thus putting patients at risk and incurring considerable expense for the national health service. We chose to audit the practice of doctors in our geriatric facility, and assessed the effect of a memoire to increase compliance. We also explore how our hospitals can learn from the experience of other centres, where the risk of litigation has brought this condition to the forefront. Compliance improved from 30.7% to 63.3%, which was statistically significant. We would suggest that a centralised and organised approach could produce even greater levels of compliance.peer-reviewe

Cost-Utility Analysis of Venous Thromboembolism Prophylaxis Strategies for People Undergoing Elective Total Hip and Total Knee Replacement Surgeries in the English National Health Service

Background: Major orthopedic surgery, such as elective total hip replacement (eTHR) and elective total knee replacement (eTKR), are associated with a higher risk of venous thromboembolism (VTE) than other surgical procedures. Little is known, however, about the cost-effectiveness of VTE prophylaxis strategies in people undergoing these procedures. Aim: The aim of this work was to assess the cost-effectiveness of these strategies from the English National Health Service perspective to inform NICE guideline (NG89) recommendations. Materials and Methods: Cost-utility analysis, using decision modeling, was undertaken to compare 15 VTE prophylaxis strategies for eTHR and 12 for eTKR, in addition to “no prophylaxis” strategy. The analysis complied with the NICE Reference Case. Structure and assumptions were agreed with the guideline committee. Incremental net monetary benefit (INMB) was calculated, vs. the model comparator (LMWH+ antiembolism stockings), at a threshold of £20,000/quality-adjusted life-year (QALY) gained. The model was run probabilistically. Deterministic sensitivity analyses (SAs) were undertaken to assess the robustness of the results. Results: The most cost-effective strategies were LMWH for 10 days followed by aspirin for 28 days (INMB = £530 [95% CI: -£784 to £1,103], probability of being most cost-effective = 72%) for eTHR, and foot pump (INMB = £353 [95% CI: -£101 to £665]; probability of being most cost-effective = 18%) for eTKR. There was considerable uncertainty regarding the cost-effectiveness ranking in the eTKR analysis. The results were robust to change in all SAs. Conclusions: For eTHR, LMWH (standard dose) for 10 days followed by aspirin for 28 days is the most cost-effective VTE prophylaxis strategy. For eTKR, the results are highly uncertain but foot pump appeared to be the most cost-effective strategy, followed closely by aspirin (low dose). Future research should focus on assessing cost-effectiveness of VTE prophylaxis in the eTKR population.Peer reviewe

Cancer and thrombosis: Managing the risks and approaches to thromboprophylaxis

Patients with cancer are at increased risk of venous thromboembolism (VTE) compared with patients without cancer. This results from both the prothrombotic effects of the cancer itself and iatrogenic factors, such as chemotherapy, radiotherapy, indwelling central venous devices and surgery, that further increase the risk of VTE. Although cancer-associated thrombosis remains an important cause of morbidity and mortality, it is often underdiagnosed and undertreated. However, evidence is accumulating to support the use of low-molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients with cancer. Not only have LMWHs been shown to be at least as effective as coumarin derivatives in this setting, but they have a lower incidence of complications, including bleeding, and are not associated with the practical problems of warfarin therapy. Furthermore, a growing number of studies indicate that LMWHs may improve survival among patients with cancer due to a possible antitumor effect. Current evidence suggests that LMWHs should increasingly be considered for the long-term management of VTE in patients with cancer

Prevention of venous thromboembolism after hip and knee replacement among older adults

BACKGROUND: Venous thromboembolism (VTE) after total hip and knee replacement is a major patient safety threat, and pharmacologic prophylaxis is generally recommended. However, clinicians disagree on the optimal prophylaxis agent. OBJECTIVE: We sought to compare effectiveness and safety of aspirin versus anticoagulants for VTE prophylaxis after hip and knee replacement. METHODS: We identified patients aged ≥ 65 years undergoing elective hip and knee replacement during 2011–2013 in 59 hospitals nationwide and included in the Institute for Health Metrics clinical database. We limited our analysis to the patients with electronic medical record of discharge prophylaxis medication. Patients were categorized into either anticoagulant or aspirin only group. VTE, major hemorrhage, cardiovascular event, and death were identified from electronic databases and validated by physician review of the source documents. We compared the 90-day risk of VTE and the composite outcome (VTE, cardiovascular events, major hemorrhage, and death) in the anticoagulant group to the aspirin group using Cox proportional hazards analysis. RESULTS: Study sample included 5648 patients with mean age 73 years. The overall number of outcome events was low. There were 35 VTE events (0.61%), 15 (0.26%) cardiovascular events, 17 major hemorrhages (0.30%), and 18 deaths (0.31%). In multivariable analysis adjusting for patient demographics and cardiovascular disease and risk factors, anticoagulation therapy was associated with decreased risk of VTE (HR 0.76, 95% CI 0.35–1.68) and the composite outcome (HR 0.80, 95% CI 0.48–1.32) although not statistically significant. CONCLUSION: Among older adults undergoing elective total hip and knee replacement in community hospitals, the 90-day risk of VTE and the composite outcome was low. We did not find any statistical difference in the risk of the outcomes between anticoagulation and aspirin. Future studies with a larger sample size and different patient population are needed to validate our results.2019-11-08T00:00:00