Low Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis

Eck, Ruben J.; Bult, Wouter; Wetterslev, Jørn; Gans, Reinold; Meijer, Karina; Horst, Iwan C C van der; Keus, Frederik

doi:10.3390/jcm8122039

Cited by 14 publications

(8 citation statements)

References 27 publications

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“…After a median follow-up period of 3.5 months, VTE occurred in 1.2% of the semuloparin group and 3.4% of the placebo group with a number needed to treat (NNT) of 45.5 and clinically relevant bleeding occurring in 2.8% of patients receiving semuloparin versus 2.0% receiving placebo [ 17 ]. Other studies of LMWH in unselected patients have similarly found NNTs in the 40–50 range [ 17 , 18 , 19 , 20 , 21 ]. When cancer patients at high risk of VTE (Khorana score of three or greater) were selected, LMWH thromboprophylaxis reduced the VTE incidence (12% in LMWH group versus 21% in observation group) but resulted in a seven-fold increase risk of bleeding [ 21 ].…”

Section: Historic and Current Approaches To Patient Selection For mentioning

confidence: 86%

Section: Historic and Current Approaches To Patient Selection For Primary Thromboprophylaxis Of Cancer-associated Thrombosismentioning

confidence: 92%

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Impact of Tumor Genomic Mutations on Thrombotic Risk in Cancer Patients

Leiva

Connors

Al‐Samkari

2020

Cancers

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Venous thromboembolism (VTE) is common in patients with cancer and is an important contributor to morbidity and mortality in these patients. Early thromboprophylaxis initiated only in those cancer patients at highest risk for VTE would be optimal. Risk stratification scores incorporating tumor location, laboratory values and patient characteristics have attempted to identify those patients most likely to benefit from thromboprophylaxis but even well-validated scores are not able to reliably distinguish the highest-risk patients. Recognizing that tumor genetics affect the biology and behavior of malignancies, recent studies have explored the impact of specific molecular aberrations on the rate of VTE in cancer patients. The presence of certain molecular aberrations in a variety of different cancers, including lung, colon, brain and hematologic tumors, have been associated with an increased risk of VTE and arterial thrombotic events. This review examines the findings of these studies and discusses the implications of these findings on decisions relating to thromboprophylaxis use in the clinical setting. Ultimately, the integration of tumor molecular genomic information into clinical VTE risk stratification scores in cancer patients may prove to be a major advancement in the prevention of cancer-associated thrombosis.

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Section: Historic and Current Approaches To Patient Selection For mentioning

confidence: 86%

Section: Historic and Current Approaches To Patient Selection For Primary Thromboprophylaxis Of Cancer-associated Thrombosismentioning

confidence: 92%

Impact of Tumor Genomic Mutations on Thrombotic Risk in Cancer Patients

Leiva

Connors

Al‐Samkari

2020

Cancers

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“…5 6 7 8 9 We previously distinguished between low, intermediate, and high dose low-molecular-weight heparin based on the summary of product characteristics and randomised controlled trial dosing regimens. 10 11 A network meta-analysis on prophylaxis in surgical patients found different intervention effects for different prophylactic low-molecular-weight heparin doses. 12 Additionally, a Cochrane meta-analysis in patients with covid-19 found no conclusive benefits of high dose low-molecular-weight heparin or unfractionated heparin over lower doses.…”

Section: Introductionmentioning

confidence: 99%

“…Pentasaccharides have been studied and registered for venous thromboembolism prevention in a single dose, but low-molecular-weight heparin and unfractionated heparin can be administered in several doses depending on the country and setting 56789. We previously distinguished between low, intermediate, and high dose low-molecular-weight heparin based on the summary of product characteristics and randomised controlled trial dosing regimens 1011. A network meta-analysis on prophylaxis in surgical patients found different intervention effects for different prophylactic low-molecular-weight heparin doses 12…”

Section: Introductionmentioning

confidence: 99%

Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis

Eck

Elling

Sutton

et al. 2022

BMJ

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Objective To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital. Design Systematic review and network meta-analysis. Data sources Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021. Eligibility criteria for selecting studies Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital. Main outcome measures Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework. Results 44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses. Conclusions Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc. Systematic review registration PROSPERO CRD42020173088.

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“… 14 During the current COVID-19 pandemic, several prophylactic doses and types of LMWH are being used worldwide; however, there are no high-quality evidence studies or recommendation for the optimal prophylactic LMWH dose. 15 …”

Section: Introductionmentioning

confidence: 99%

Therapeutic dosing of low-molecular-weight heparin may decrease mortality in patients with severe COVID-19 infection

Canoğlu¹,

Şaylan²

2020

Ann Saudi Med

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BACKGROUND: Venous thromboembolism or extensive thrombosis is relatively common in patients with severe COVID-19 infection and has been associated with increased mortality. During the current COVID-19 pandemic, several prophylactic doses and types of low-molecular-weight heparin (LMWH) are being used worldwide; however, there are no high-quality studies or recommendations for an optimal prophylactic LMWH dose. OBJECTIVES: Investigate the relationship between coagulation parameters and the LMWH dose, and mortality and ICU admission in hospitalized patients with severe COVID-19 pneumonia. DESIGN: Retrospective. SETTING: Tertiary care hospital. PATIENTS AND METHODS: Data on clinical features, coagulation parameters and anticoagulant medications of inpatients with severe COVID-19 were collected for the period between 11 March 2020 and 31 April 2020. MAIN OUTCOME MEASURES: Mortality and ICU admission for prophylactic dose LMWH (0.5 mg/kg twice daily) and therapeutic dose LMWH (1 mg/kg twice daily). SAMPLE SIZE: 154 cases. RESULTS: Ninety-eight (63.6%) patients were treated with the LMWH prophylactic dose and 56 (36.4%) patients were treated with the therapeutic dose. Forty-four (44.9%) of 98 patients using the prophylactic dose LMWH died, while 10 (17.9%) of 56 patients using the therapeutic dose LMWH died ( P =.001). Mortality was 6.4-fold higher in the prophylactic dose LMWH users than in the therapeutic dose LMWH users (OR=6.5, 95% CI: 2.4–17.6, P <.001). CONCLUSIONS: Therapeutic dosing of LMWH may decrease mortality in patients with severe COVID-19 infected pneumonia. More aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies. LIMITATIONS: Lack of information about bleeding complications. LMWH was not compared with other anticoagulant therapies. There was no comparison between our two groups on the APACHE score. Used different doses of LMWH in different clinics in our hospital. Single-center, retrospective study. CONFLICT OF INTEREST: None.

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Low Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis

Cited by 14 publications

References 27 publications

Impact of Tumor Genomic Mutations on Thrombotic Risk in Cancer Patients

Impact of Tumor Genomic Mutations on Thrombotic Risk in Cancer Patients

Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis

Therapeutic dosing of low-molecular-weight heparin may decrease mortality in patients with severe COVID-19 infection

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