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1.
The role of low molecular weight heparin on recurrent pregnancy loss: A systematic review and meta-analysis.
Jiang, F, Hu, X, Jiang, K, Pi, H, He, Q, Chen, X
Taiwanese journal of obstetrics & gynecology. 2021;(1):1-8
Abstract
To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were retrieved, and the systematic evaluation was conducted. PubMed, Embase, and Cochrane library databases were searched by using keywords, including low-molecular-weight heparin or LMWH, and recurrent miscarriage or recurrent pregnancy loss in pregnant women from their earliest data to February 2020. Two investigators independently evaluated eligibility. Risk ratios (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, this meta-analysis was performed using random-effect model due to the high heterogeneity among these eight studies. A total of eight RCTs involving 1854 participants were included in the meta-analysis involving 963 patients with RPL who were prescribed LMWH (enoxaparin, tinzaparin, or dalteparin) alone and 891 patients who were treated with no LMWH interventions (placebo, folic acid or non-treatment) were compared. Pooled data from the remaining eight RCTs showed the differences between intervention groups and control groups. Compared with control groups, LMWH had significantly improved live births (RR,1.19; 95%CI, 1.03 to 1.38; P = 0.02), and reduced miscarriage rates (RR, 0.62; 95%CI, 0.43 to 0.91; P = 0.01). The study suggested that LMWH could improve the live births and reduce the miscarriage rates of RPL. Therefore, LMWH might be a good treatment choice for women with unexplained PRL.
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2.
[Low-molecular-weight heparins for cancer-associated thromboembolism: What place in 2019?].
Debourdeau, P, Cossou-Gbeto, C, Takam-Sohwe, T, Laroche, JP
Bulletin du cancer. 2020;(2):224-233
Abstract
According to international clinical practice guidelines, low-molecular-weight heparins are advocate for the treatment and the prevention of cancer associated thrombosis. Direct oral anticoagulants recently introduced represent an alternative to vitamin K antagonists and low-molecular-weight heparins since their use doesn't require coagulation monitoring or daily subcutaneous injections. Recent studies comparing direct oral anticoagulants and low-molecular-weight heparins have shown a trend towards a reduction of venous thromboembolism events of direct oral anticoagulants but an increased risk of major bleeding. Recent French inter-group recommendations on the treatment of venous thromboembolism in cancer patients, favor low molecular weight heparins over direct oral anticoagulants as curative agents. In the light of recent studies, the objective of this review is to re-evaluate the place of low-molecular-weight heparins in the management of patents with cancer-associated thrombosis and to focus on the recent updates of international guidelines.
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3.
Early detection of the existence or absence of the treatment effect: A cumulative meta-analysis.
Laporte, S, Chapelle, C, Trone, JC, Bertoletti, L, Girard, P, Meyer, G, Safieddine, M, Cucherat, M, Ollier, E, Mismetti, P, et al
Journal of clinical epidemiology. 2020;:24-33
Abstract
OBJECTIVES An unexpected promising effect of low molecular weight heparins (LMWHs) on survival in patients with cancer was observed in early trials in post hoc subgroup analyses but not found in more recent trials. To highlight a possible regression over time toward the lack of the antitumoral effect of LMWHs, we performed a cumulative meta-analysis of survival data from randomized controlled trials (RCTs). STUDY DESIGN AND SETTING Medical databases were searched to identify RCTs comparing, in patients with cancer, LMWHs with placebo or no treatment in patients free of venous thromboembolism (VTE), or to vitamin K antagonists in patients who experienced an acute VTE in overall survival. The cumulative hazard ratio (HR) was estimated after each study inclusion in chronological order. RESULTS Twenty-three studies (12,970 patients) were included. The cumulative meta-analysis of the earlier trials showed a significant improvement in overall survival with LMWHs. This apparent benefit then gradually regressed over time toward an absence of the effect of LMWHs on survival (HR: 0.98 [95% confidence interval, 0.93; 1.03]). CONCLUSION Despite supportive experimental data and early clinical findings, the promising antitumoral effect of LMWHs in patients with cancer gradually vanished over time toward a lack of impact on overall survival. This result suggests 'p-hacking' and selective reporting of the positive results from post hoc subgroup analyses in the early studies.
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4.
Perioperative Management in Patients Using Vitamin K Antagonists: Observational Cohort Study.
Burggraaf, JLI, van Rein, N, van der Meer, FJM, Lijfering, WM
Thrombosis and haemostasis. 2020;(3):495-504
Abstract
BACKGROUND The benefit of periprocedural bridging with low-molecular-weight heparin (LMWH) in patients with atrial fibrillation has been contested by the publication of the BRIDGE trial. OBJECTIVE This article determines whether publication of the BRIDGE trial has led to less bridging procedures and better patient outcomes (i.e., a composite of thromboembolism, major bleeding, and death) in patients undergoing invasive procedures at the Leiden Anticoagulation Clinic, the Netherlands. METHODS We identified all procedures that required vitamin K antagonist interruption. Procedures were divided in a period before (2014-2016; 22 months) and after the publication of the BRIDGE trial (2016-2017; 22 months). Cumulative incidences 30 days postprocedure and relative risks of thromboembolic events, major bleeding, and mortality were calculated. RESULTS A total of 4,892 and 4,237 eligible procedures were performed in 2014 to 2016 and 2016 to 2017, respectively. The cumulative incidence of thromboembolism was 0.5% in 2014 to 2016 compared with 0.3% in 2016 to 2017; adjusted odds ratio (OR) 0.60 (95% confidence interval [CI] 0.30-1.21). The cumulative incidence of major bleeding was 1.0% in the 2014 to 2016 period as compared with 1.3% in the 2016 to 2017 period; adjusted OR was 1.27 (95% CI 0.85-1.90). The adjusted OR of the composite endpoint was 1.05 (95% CI 0.74-1.48). The frequency of bridging with LMWH (14.8% in 2014-2016 vs. 16.6% in 2016-2017) as well as mean CHA2DS2-VASc scores of patients receiving bridging did not change after publication of the BRIDGE trial. CONCLUSION We showed that despite publication of the BRIDGE trial, the frequency of bridging with LMWH and patient outcomes regarding bleeding complications did not change.
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5.
Efficacy and Safety of Low-Molecular-Weight Heparin on Prevention of Venous Thromboembolism after Laparoscopic Operation for Gastrointestinal Malignancy in Japanese Patients: A Multicenter, Open-Label, Prospective, Randomized Controlled Trial.
Obitsu, T, Tanaka, N, Oyama, A, Ueno, T, Saito, M, Yamaguchi, T, Takagi, A, Rikiyama, T, Unno, M, Naitoh, T, et al
Journal of the American College of Surgeons. 2020;(5):501-509.e2
Abstract
BACKGROUND The risk of venous thromboembolism (VTE) after surgery for malignancy in Japanese patients is unclear; therefore, standard prevention protocols have not been established, especially for minimally invasive procedures. We aimed to investigate the additional effect of low molecular weight heparin (LMWH) on prevention of VTE after laparoscopic surgery for gastrointestinal malignancy. STUDY DESIGN From February 2013 to January 2017, 400 patients scheduled for laparoscopic surgery were included. Cases were randomly allocated to the physical therapy group (Control group; 201 patients) or to the combination-therapy group (LMWH group; 199 patients), in which enoxaparin sodium (20 mg [= 2000 IU] twice a day) was administered for 1 week postoperatively in addition to the physical therapy. A diagnosis of VTE was made by contrast-enhanced CT or ultrasonography when symptomatic or D-dimer was ≥10 μg/mL. RESULTS VTE was observed in 1.2% and 4.0% of patients in the LMWH and Control groups, respectively (odds ratio [OR] 0.3, 95% confidence interval [CI] 0.03-1.53). Pulmonary embolism was confirmed only in the Control group (1.7%). No major bleeding occurred in either group. Logistic multiple regression analysis revealed that surgical time extension (OR 1.02, 95% CI 1.00-1.04) was a risk factor of VTE, while administration of LMWH (OR 0.21, 95% CI 0.03-0.99), male sex (OR 0.12, 95% CI 0.01-0.60), and early cancer (OR 0.17, 95% CI 0.02-0.82) reduced the risk of VTE. CONCLUSIONS Postoperative LMWH administration is safe. The additional effect of LMWH administration on the physical therapy was not statistically proven in this study. However, it could be useful for the patients with risk factors such as female sex, long operation time, and higher cancer stage.
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6.
Low-Molecular-Weight Heparin in Cancer Patients: Overview and Indications.
Voigtlaender, M, Langer, F
Hamostaseologie. 2019;(1):67-75
Abstract
Although venous thromboembolism (VTE) is a well-known cause of death in patients with cancer, both its treatment and prevention remain a challenge in daily practice. Direct oral anticoagulants have emerged as safe and efficacious alternatives to vitamin K antagonists in the general population, and recent clinical trials also support their use in select patients with cancer-associated VTE. Despite this, low-molecular-weight heparins (LMWHs), a comparatively ancient class of antithrombotic drugs, remain the anticoagulants of choice in many indications relevant to modern haematology and oncology. In addition to the treatment of established VTE, these indications include VTE prophylaxis in surgical or acutely ill, hospitalized medical cancer patients as well as the prevention of VTE in high-risk patients undergoing ambulatory chemotherapy. In a constantly changing landscape of approved anticancer agents, this review article summarizes pivotal clinical trial data and guideline recommendations regarding the use of LMWH in haematological and oncological patients, who constitute a highly vulnerable patient population due to their increased risk for both bleeding and VTE recurrence.
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7.
Risk factors for and clinical management of venous thromboembolism during pregnancy.
Rybstein, MD, DeSancho, MT
Clinical advances in hematology & oncology : H&O. 2019;(7):396-404
Abstract
Venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism, is one of the leading causes of non-obstetric maternal death in the United States. Physiologic and anatomic changes associated with pregnancy set the stage for a hypercoagulable state. In addition, other risk factors-including those associated with certain fetal characteristics such as low birth weight or stillbirth-have been correlated with an increased risk for VTE. Women with a personal or strong family history of VTE, as well as documented thrombophilia, represent a unique group in whom antepartum and/or postpartum prophylaxis can be considered. The choice of anticoagulant therapy for either treatment or prophylaxis in most cases is heparin, most commonly low-molecular-weight heparin. This is owing to the fact that vitamin K antagonists and the direct oral anticoagulants are contraindicated in pregnancy because of potential teratogenicity. With careful management and vigilant monitoring, appropriate anticoagulation can be used safely and effectively to improve patient outcomes.
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8.
Starting anticoagulation with vitamin k antagonists alone or with concomitant low-molecular weight heparin for non-valvular atrial fibrillation.
Sarrate, E, Gual-Capllonch, F, Sorigue, M
European journal of internal medicine. 2019;:e14-e15
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9.
Low-molecular-weight heparins for the prevention of recurrent venous thromboembolism in patients with cancer: A systematic literature review of efficacy and cost-effectiveness.
Dranitsaris, G, Shane, LG, Woodruff, S
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2019;(1):68-75
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Abstract
BACKGROUND Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value. METHODS A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed. RESULTS Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents. CONCLUSIONS The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer.
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Acute non-cirrhotic portal vein thrombosis : review.
Salembier, A, Verhamme, M, Verhamme, P, Van Moerkercke, W
Acta gastro-enterologica Belgica. 2018;(2):318-322
Abstract
A 35-year-old man with a medical history of myocardial infarction, presenting with fever, general malaise and vague abdominal discomfort, was diagnosed with a portomesenteric venous thrombosis and acute cytomegalovirus (CMV) infection. Thrombophilia screening resulted in detection of heterozygosity for factor II G20210A gene mutation. Low molecular weight heparin in therapeutic dose was started, followed by disappearance of thrombus on imaging CT two months after diagnosis. The multifactorial origin of portal thrombosis and the importance of awareness of the link between CMV infection and an increased risk of thrombosis is emphasized with this case and review of the literature. Identifying CMV infection as a trigger for thrombosis can help to avoid extended anticoagulation. Acute non-cirrhotic PVT is a rare but probably underestimated condition as symptoms may be discrete or non-specific. The origin of portal thrombosis is frequently multifactorial. Recent literature has emphasized the increasing prevalence of CMV-induced PVT in immunocompetent patients. The multifactorial origin of portal thrombosis and the importance of awareness of the link between CMV infection and an increased risk of thrombosis is emphasized with this review of the literature and included case. Identifying CMV infection as a trigger for thrombosis can help to avoid extended anticoagulation.