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Seminars in Thrombosis and Hemostasis Nov 2020Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching...
Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching epidemic proportions worldwide, the optimal dosage for obese patients has not been established for most anticoagulants, including low-molecular-weight heparin (LMWH), non-vitamin K antagonist oral anticoagulants (NOAC), and pentasaccharides (fondaparinux). The aim of the present systematic review was to summarize the current knowledge and provide recommendations on dosage of LMWH, NOAC, and fondaparinux in obese patients (body mass index [BMI] ≥ 30 kg/m or body weight ≥ 100 kg). Based on a systematic search in PubMed and Embase, a total of 72 studies were identified. For thromboprophylaxis with LMWH in bariatric surgery ( = 20 studies), enoxaparin 40 mg twice daily, dalteparin 5,000 IE twice daily, or tinzaparin 75 IU/kg once daily should be considered for patients with BMI ≥ 40 kg/m. For thromboprophylaxis with LMWH in nonbariatric surgery and in medical inpatients ( = 8 studies), enoxaparin 0.5 mg/kg once or twice daily or tinzaparin 75 IU/kg once daily may be considered in obese patients. For treatment with LMWH ( = 18 studies), a reduced weight-based dose of enoxaparin 0.8 mg/kg twice daily should be considered in patients with BMI ≥ 40 kg/m, and no dose capping of dalteparin and tinzaparin should be applied for body weight < 140 kg. As regards NOAC, rivaroxaban, apixaban, or dabigatran may be used as thromboprophylaxis in patients with BMI < 40 kg/m ( = 4 studies), whereas rivaroxaban and apixaban may be administered to obese patients with VTE or AF, including BMI > 40 kg/m, at standard fixed-dose ( = 20 studies). The limited available evidence on fondaparinux ( = 3 studies) indicated that the treatment dose should be increased to 10 mg once daily in patients weighing > 100 kg.
Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Obesity
PubMed: 33368113
DOI: 10.1055/s-0040-1718405 -
Taiwanese Journal of Obstetrics &... Mar 2020Due to the morbidity and mortality of mothers and fetuses developed by preeclampsia, preventive approaches have always been taken into account in high risk individuals....
Due to the morbidity and mortality of mothers and fetuses developed by preeclampsia, preventive approaches have always been taken into account in high risk individuals. Systematic review studies contribute to make a better decision about the results of such studies. Accordingly, this study strived to systematically study the factors effective in the prevention of preeclampsia. The MEDLINE, ISI Web of Science, PubMed, Scopus, Google Scholar, and Proquest databases were systematically reviewed between January 2000 and May 2019. The quality of the studies was analyzed using the CONSORT checklist. A study was conducted on 29 quality interventional studies; 28 of which were RCT type, and on various factors such as anticoagulants (heparin, enoxaparin, Dalteparin and Nadroparin), aspirin, paravastatin, nitric oxide, yoga, micronutrients Such as l-Arginine, Folic Acid, Vitamin E and C, Phytonutrient, Lycopene and Vitamin D alone or in combination with Calcium. The results of this study showed that low molecular weight heparin, enoxaparin, PETN, yoga, L arginine, folic acid, vitamin D prevented preeclampsia alone or combined with calcium.
Topics: Arginine; Calcium; Drug Therapy, Combination; Enoxaparin; Female; Folic Acid; Heparin, Low-Molecular-Weight; Humans; Pentaerythritol Tetranitrate; Pre-Eclampsia; Pregnancy; Prenatal Care; Vitamin D; Yoga
PubMed: 32127134
DOI: 10.1016/j.tjog.2020.01.002 -
Medicina (Kaunas, Lithuania) Oct 2023: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs),... (Meta-Analysis)
Meta-Analysis Review
: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. : We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). : It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I 0%). : Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, albeit with no statistical difference. Statistical significance was observed for no major clinically relevant bleeding but not for major bleeding.
Topics: Humans; Dalteparin; Venous Thromboembolism; Anticoagulants; Hemorrhage; Neoplasms
PubMed: 37893585
DOI: 10.3390/medicina59101867 -
Life (Basel, Switzerland) Jan 2024This systematic review addresses the crucial role of anticoagulation in microsurgical procedures, focusing on free flap reconstruction and replantation surgeries. The... (Review)
Review
This systematic review addresses the crucial role of anticoagulation in microsurgical procedures, focusing on free flap reconstruction and replantation surgeries. The objective was to balance the prevention of thrombotic complications commonly leading to flap failure, with the risk of increased bleeding complications associated with anticoagulant use. A meticulous PubMed literature search following Evidence-Based-Practice principles yielded 79 relevant articles, including both clinical and animal studies. The full-texts were carefully reviewed and evaluated by the modified Coleman methodology score. Clinical studies revealed diverse perioperative regimens, primarily based on aspirin, heparin, and dextran. Meta-analyses demonstrated similar flap loss rates with heparin or aspirin. High doses of dalteparin or heparin, however, correlated with higher flap loss rates than low dose administration. Use of dextran is not recommended due to severe systemic complications. In animal studies, systemic heparin administration showed predominantly favorable results, while topical application and intraluminal irrigation consistently exhibited significant benefits in flap survival. The insights from this conducted systematic review serve as a foundational pillar towards the establishment of evidence-based guidelines for anticoagulation in microsurgery. An average Coleman score of 55 (maximum 103), indicating low overall study quality, however, emphasizes the need for large multi-institutional, randomized-clinical trials as the next vital step.
PubMed: 38255697
DOI: 10.3390/life14010082 -
The Cochrane Database of Systematic... Dec 2021Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. (Review)
Review
BACKGROUND
Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE.
OBJECTIVES
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.
SEARCH METHODS
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.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE.
DATA COLLECTION AND ANALYSIS
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.
MAIN RESULTS
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.
AUTHORS' CONCLUSIONS
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.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Venous Thromboembolism
PubMed: 34878173
DOI: 10.1002/14651858.CD006649.pub8 -
BMC Pregnancy and Childbirth Jan 2024To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia.
SEARCH STRATEGY
PubMed, Embase and the Cochrane library were searched for articles published before 1st August 2022 using the combination keywords "preeclampsia", "Low Molecular Weight Heparin", "LMWH", "Heparin, Low Molecular Weight", "Dalteparin", "Nadroparin", and "Tinzaparin".
SELECTION CRITERIA
Randomized controlled trials evaluating the use of LMWH in pregnant women at high risk of preeclampsia without thrombophilia.
DATA COLLECTION AND ANALYSIS
Ten studies were included in the meta-analysis (1758 patients in total). Outcomes were expressed as relative risk (RR) with 95% confidence intervals (CI).
RESULTS
LMWH reduced the incidence of PE (RR = 0.67; 95% CI = 0.50-0.90; P = 0.009) in high risk pregnant women without thrombophilia. Subgroup analysis found that the prophylactic effect of LMWH was only significant in studies using low-dose aspirin (LDA) as the primary intervention. The combination of LMWH and LDA was also effective for the prevention of preterm birth and fetal growth restriction, but had no effect on the incidence of placenta abruption.
CONCLUSION
For women at high risk of developing preeclampsia without thrombophilia, the combination of LMWH and low-dose aspirin is effective for the prevention of preeclampsia, preterm birth and fetal growth restriction and is superior to LDA alone.
Topics: Female; Infant, Newborn; Humans; Pregnancy; Heparin, Low-Molecular-Weight; Pre-Eclampsia; Pregnancy, High-Risk; Premature Birth; Fetal Growth Retardation; Aspirin; Heparin; Nadroparin; Thrombophilia; Anticoagulants
PubMed: 38233773
DOI: 10.1186/s12884-023-06218-9 -
Frontiers in Cardiovascular Medicine 2020Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of...
Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). However, direct head-to-head comparisons among DOACs are lacking, and almost no net clinical benefit (NCB) analysis has been performed in patients with CAT. We systematically searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting on recurrent VTE, major bleeding, or clinically relevant bleeding events in patients with CAT who received DOACs and low-molecular-weight heparins. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effect model. Surface under the cumulative ranking curve (SUCRA) values were calculated, and a trade-off analysis was performed to estimate the NCB. Overall, four RCTs involving 2,894 patients were enrolled. DOACs were more effective than dalteparin in reducing the risk of recurrent VTE (RR: 0.62, 95% CI: 0.44-0.87), with a comparative risk of major bleeding (RR: 1.33, 95% CI: 0.84-2.11) and an increased risk of clinically relevant bleeding (RR: 1.45, 95% CI: 1.05-1.99). No significant difference was observed among individual anticoagulants in terms of recurrent VTE and major bleeding. With respect to the ranking of each anticoagulant for the primary outcome, edoxaban (SUCRA: 69.2) was more effective than dalteparin (SUCRA: 60.7), rivaroxaban (SUCRA: 60.7), and apixaban (SUCRA: 25.5) in reducing VTE recurrence. For major bleeding, apixaban (SUCRA: 76.3) had the highest cumulative ranking probability, followed by edoxaban (SUCRA: 66.4), dalteparin (SUCRA: 28.8), and rivaroxaban (SUCRA: 28.5). Similar results were observed for clinically relevant bleeding. In terms of both benefit and safety outcomes, DOACs, especially edoxaban, seemed to confer a better NCB profile than dalteparin. DOACs are a safe and effective alternative therapy to dalteparin in patients with CAT. Among them, edoxaban might provide a good risk-to-benefit balance. However, because of the lack of head-to-head studies, further investigations are needed to confirm our findings.
PubMed: 33304929
DOI: 10.3389/fcvm.2020.586020 -
JACC. CardioOncology Sep 2020Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli....
BACKGROUND
Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli. Patients with cancer may also have an increased risk of bleeding with anticoagulant treatment. Recent trials have reported that direct oral anticoagulants (DOACs) are noninferior to the low-molecular-weight heparin, dalteparin, in preventing VTE, but have a higher bleeding rate.
OBJECTIVES
This study compared the efficacy and risks of DOACs versus dalteparin in patients with cancer-related VTEs across all randomized controlled trials (RCTs).
METHODS
This study performed a systematic analysis of RCTs published in PubMed, SCOPUS, and Google Scholar from September 1, 2007 through March 31, 2020 that reported clinical outcomes of treatment with DOACs versus dalteparin in patients with cancer with acute VTE. Two investigators independently performed study selection and data extraction. Extracted data were recorded and exported to statistical software for all analyses (OpenMetaAnalyst).
RESULTS
This study included 4 randomized trials (N = 2,907). Compared with DOACs, dalteparin was associated with higher VTE recurrence (risk ratio [RR]: 1.55; 95% confidence interval [CI]: 1.19 to 2.03; p = 0.001), whereas clinically relevant nonmajor bleeding (CRNMB) was significantly less frequent with dalteparin than that with DOACs (RR: 0.68; 95% CI: 0.54 to 0.86; p = 0.001). The risk of CRNMB was largely observed with patients with gastrointestinal malignancies. No significant differences were observed in major bleeding (RR: 0.74; 95% CI: 0.52 to 1.06; p = 0.11).
CONCLUSIONS
DOACs were noninferior to dalteparin in preventing VTE recurrence in patients with cancer without a significantly increased risk of major bleeding. However, DOACs were associated with higher rates of CRNMB compared with dalteparin, primarily in patients with gastrointestinal malignancies.
PubMed: 34396250
DOI: 10.1016/j.jaccao.2020.06.001 -
Cureus Jul 2023Venous thromboembolism (VTE) is a condition often seen in patients diagnosed with cancer and is recognized as a predictor of poor outcomes in these patients. The... (Review)
Review
Venous thromboembolism (VTE) is a condition often seen in patients diagnosed with cancer and is recognized as a predictor of poor outcomes in these patients. The probability of VTE recurring is generally higher in people with cancer than in those without; hence, addressing this issue is essential when making healthcare decisions. Therefore, our systematic review was primarily designed to compare low-weight- molecular heparin (LMWH) to warfarin in reducing recurrent VTE among cancer patients. However, other outcomes were also evaluated, such as mortality and bleeding events observed more in cancer patients. The selection of relevant articles was carried out using a database search and a manual search, which involved reviewing reference lists of articles eligible for inclusion in the current review. The methodological quality of each included study was then assessed using Cochrane's risk of bias tool in the Review Manager software (RevMan 5.4.1). Additionally, pooled results were examined using the Review Manager software and presented as forest plots. Our search of electronic databases elicited a total of 2163 articles, of which only six were deemed eligible for inclusion and analysis. Data pooled from the six studies demonstrated the effectiveness of LMWH in minimizing the reoccurrence of VTE over warfarin [risk ratio (RR): 0.67; 95% CI: 0.47 - 0.95; p = 0.03]. However, LMWH had a similar effect statistically as warfarin on the major bleeding events (RR: 1.05; 95% CI: 0.62 - 1.77; p = 0.85), minor bleeding events (RR: 0.80; 95% CI: 0.54 - 1.20; p = 0.28), and all-cause mortality (RR: 1.00; 95% CI: 0.88 - 1.13; p = 0.99). While LMWH demonstrated its effectiveness in minimizing the incidence of VTE recurrence over warfarin in cancer patients, it had no statistical difference in terms of mortality or bleeding events when compared to warfarin. Based on our findings, we recommend that LMWH continues to be used as a first-line treatment regimen to mitigate recurrent VTE in cancer patients.
PubMed: 37533609
DOI: 10.7759/cureus.41268 -
Frontiers in Pharmacology 2019Venous thromboembolism (VTE) is a common complication in patients with cancer. Direct oral anticoagulants (DOACs) have been proved to be effective on anticoagulation...
Efficacy and Safety of Direct Oral Anticoagulants for Secondary Prevention of Cancer-Associated Thrombosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies.
Venous thromboembolism (VTE) is a common complication in patients with cancer. Direct oral anticoagulants (DOACs) have been proved to be effective on anticoagulation therapy in many diseases. However, the efficacy and the safety of DOACs in the secondary prevention of cancer-associated thrombosis (CAT) remain unclear. To assess the value of DOACs in patients with CAT, we performed a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Medline, Embase, and the Cochrane Library were searched from their earliest date through to June 2018. Two investigators independently assessed eligibility. Data were extracted by one investigator and verified by the second investigator. The efficacy outcome of this study was recurrent VTE, whereas the safety outcome was major and clinically relevant nonmajor bleeding. Relative risks (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, the Mantel-Haenszel fixed-effects or random-effects models were used. A total of nine articles (six randomized controlled trials and three prospective studies) involving 2,697 patients with CAT who were prescribed DOACs (apixaban, edoxaban, rivaroxaban, or dabigatran) and 2,852 patients who were prescribed traditional anticoagulants [vitamin K antagonists (VKAs), low molecular weight heparin (LMWH), dalteparin, or enoxaparin] were compared. VTE recurrence in the DOAC group was significantly lower than that observed in the traditional anticoagulant group (RR: 0.60; 95%CI: 0.49-0.75; : 0%; < 0.00001). No significant difference in bleeding risk between both groups was found (RR: 0.95; 95%CI: 0.67-1.36; : 75%; = 0.79). Our findings showed that anticoagulant therapy with DOACs may be more effective than traditional anticoagulants to prevent recurrent VTE in patients with CAT, while the safety of DOACs may be equal to that of traditional anticoagulants. These findings support the use of DOACs as the first-line therapy for secondary prevention of CAT in most cancer patients.
PubMed: 31354488
DOI: 10.3389/fphar.2019.00773