Low Molecular Weight Heparin and Bleeding in Patients with Severe Renal Failure: A Meta-Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 907-907
Author(s):  
Wendy Lim ◽  
Francesco Dentali ◽  
John Eikelboom ◽  
Mark A. Crowther
Keyword(s):  
Molecular Weight ◽  
Renal Function ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Low Molecular Weight ◽  
Severe Renal Failure ◽  
Increased Risk ◽  
Standard Weight

Abstract Background: Dose adjustment or monitoring of low molecular weight heparin (LMWH) is commonly recommended in patients with severe renal insufficiency (creatinine clearance [CrCl] ≤ 30 ml/min) but little evidence supports this recommendation. Purpose: To compare the risk of major bleeding in LMWH-treated patients with CrCl ≤ 30 ml/min versus > 30 ml/min using standard weight-adjusted therapeutic LMWH doses, empirically adjusted LMWH doses and prophylactic LMWH doses. Data sources: Electronic databases (MEDLINE, EMBASE, Cochrane Library), reference lists and contact with experts. Study selection: Observational or subgroups of randomized studies that included non-dialyzed patients with varying degrees of renal function who were treated with LMWH and which reported CrCl and major bleeding. Data extraction: Two reviewers independently selected studies and extracted data on patient characteristics, renal function, LMWH treatment and major bleeding. The pooled relative risk (RR) of major bleeding in patients with CrCl ≤ 30 versus > 30 ml/min was calculated by the Mantel-Haenszel method. Data synthesis: In 12 studies involving 4971 patients (10 studies of 4741 patients using enoxaparin; 2 studies of 230 patients using tinzaparin), LMWH significantly increased the risk of major bleeding in patients with CrCl ≤ 30 compared with > 30 ml/min (5.0% vs. 2.4%, RR 2.34, 95% confidence interval [CI]: 1.46 to 3.74; P = 0.0004; number needed to harm [NNH] = 38). When analyzed according to LMWH preparation, increased major bleeding was evident in studies of standard weight-adjusted therapeutic dose enoxaparin (8.3% vs. 2.4%, RR 2.96; 95% CI: 1.63 to 5.37, NNH = 17) but not in studies using empirically adjusted enoxaparin doses (0.9% vs. 1.9%, RR 1.06; 95% CI: 0.23 to 4.97), P for heterogeneity = 0.82. There were insufficient studies using tinzaparin and prophylactic doses of enoxaparin. Limitations: Only 2 LMWH preparations were evaluated and only 2 studies used tinzaparin. Data are observational and the potential for confounding cannot be excluded. Conclusions: Non-dialysis dependent patients with CrCl ≤ 30 ml/min who are treated with therapeutic doses of enoxaparin have an increased risk of major bleeding. Empiric dose reduction of enoxaparin may reduce the risk of bleeding and merits further evaluation. No conclusions can be drawn regarding other LMWHs.

Low molecular weight heparin (LMWH) for primary thrombophylaxis in patients with solid malignancies: Systematic review and meta-analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20595-e20595
Author(s):  
Irit Ben-Aharon ◽  
Salomon M. Stemmer ◽  
Ofer Shpilberg ◽  
Aaron Sulkes ◽  
Anat Gafter-Gvili
Keyword(s):  
Molecular Weight ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Primary Prophylaxis ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Low Molecular Weight ◽  
Solid Malignancies ◽  
Increased Risk

e20595 Background: Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism (VTE). The role of low molecular weight heparin (LMWH) as antithrombotic prophylaxis has been appraised in several studies, yielding conflicting results. We performed a meta-analysis of all randomized controlled trials (RCTs) which evaluated the addition of LMWH as primary prophylaxis in patients with solid malignancies while receiving chemotherapy. Methods: RCTs were identified by searching the Cochrane Library, MEDLINE databases and conference proceedings. Relative risks (RR) of thrombotic events, mortality as well as adverse events were estimated and pooled. Results: Nine trials met the inclusion criteria, and evaluated a total of 6691 patients. Primary prophylaxis with LMWH reduced both symptomatic VTEs: (RR 0.47, 95% CI(0.32 to 0.69)) and the rate of pulmonary embolism(PE): (RR 0.51, 95% CI(0.30 to 0.86)).Symptomatic DVT was reduced as well (RR 0.35, 95% CI(0.21 to 0.60). Meta-analysis of six trials which reported survival outcomes revealed no statistically significant benefit for LMWH in 1 year mortality rates (RR 0.93, 95% CI(0.83 to1.04)). There was no significant increase in major bleeding events. Conclusions: LMWH reduces the incidence of symptomatic VTE and PE in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. Nevertheless, LMWH had no significant effect on survival outcomes. Future studies should delineate whether specific populations may derive a survival benefit from LMWH primary prophylaxis.

The Relationship between Use of Low Molecular Weight Heparin during Pregnancy and Risk of Peripartum Adverse Events: A Meta-Analysis

2021 ◽  
Vol 8 (11) ◽  
Author(s):  
Xiaorong Y ◽  
◽  
Shan L ◽  
Shengji S ◽  
Tao S ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Adverse Events ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Premature Delivery ◽  
Low Molecular Weight ◽  
Significant Difference ◽  
Fetal Complications

Introduction: To summarize the trials investigated on relationship between low molecular weight heparin use during pregnancy and peripartum adverse events. Meta-analysis was performed to evaluate the effect of Low Molecular Weight Heparin (LMWH) on maternal and fetal complications. Methods: Electronic research was performed in Cochrane Library, MEDLINE and EMBASE through October 2020. The primary outcome was the incidence of maternal and fetal complications during peripartum period. RevMan 5.3 was used for data analysis. Results: 11 articles were finally included. Meta-analysis showed there was no significant difference in abortion, premature delivery, stillbirth, preeclampsia and postpartum hemorrhage events between pregnant women who used LMWH and those who not. Conclusion: Using LMWH in pregnant women does not increase pregnancy related maternal and fetal complications.

scholarly journals A Systematic Review and a Meta-Analysis Comparing Prophylactic and Therapeutic Low Molecular Weight Heparins for Mortality Reduction in 32,688 COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Riccardo Giossi ◽  
Danilo Menichelli ◽  
Arianna Pani ◽  
Elena Tratta ◽  
Alessandra Romandini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Low Molecular Weight ◽  
Full Dose ◽  
Prophylactic Dose ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Therapeutic Doses

Background: Antithrombotic treatment, including low molecular weight heparin (LMWH) or unfractionated heparin (UFH), has been proposed as a potential therapy for coronavirus disease 2019 (COVID-19) to lower diffuse intravascular clotting activation. However, it is unclear whether prophylactic or therapeutic doses have similar efficacy in reducing mortality.Methods: We performed a systematic review (PROSPERO registration CRD42020179955) and meta-analysis including observational cohort studies and randomized controlled trials (RCT) evaluating the effectiveness of heparins (either LMWH, UFH, or fondaparinux) in COVID-19 patients. Heparin treatment was compared to no anticoagulation. A subgroup analysis on prophylactic or therapeutic doses compared to no anticoagulation was performed. Prophylactic dose was also compared to full dose anticoagulation. Primary endpoint was all-cause mortality. Secondary endpoints were major bleeding and length of hospital stay (LOS).Results: 33 studies (31 observational, 2 RCT) were included for a total overall population of 32,688 patients. Of these, 21,723 (66.5%) were on heparins. 31 studies reported data on all-cause mortality, showing that both prophylactic and full dose reduced mortality (pooled Hazard Ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.69 and HR 0.56, 95% CI 0.47-0.66, respectively). However, the full dose was associated with a higher risk of major bleeding (Odds Ratio [OR] 2.01, 95% CI 1.14–3.53) compared to prophylactic dose. Finally, LOS was evaluated in 3 studies; no difference was observed between patients with and without heparins (0.98, −3.87, 5.83 days).Conclusion: Heparin at both full and prophylactic dose is effective in reducing mortality in hospitalized COVID-19 patients, compared to no treatment. However, full dose was associated with an increased risk of bleeding.Systematic Review Registration: https://clinicaltrials.gov/, identifier CRD42020179955

Low Molecular Weight Heparin Administered once versus twice Daily in Patients with Venous Thromboembolism

2001 ◽  
Vol 86 (10) ◽  
pp. 980-984 ◽  
Author(s):  
Francis Couturaud ◽  
Jim Julian ◽  
Clive Kearon
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Daily Administration ◽  
Cochrane Library ◽  
Low Molecular Weight ◽  
Once Daily ◽  
Acute Venous Thromboembolism

Summary Background. Low molecular weight heparin is as effective and safe as unfractionated heparin for treatment of acute venous thromboembolism. It is uncertain whether low molecular weight heparin should be administered once-daily or twice-daily in this setting. Method. A meta-analysis of randomized studies which directly compared once- and twice-daily administration of low molecular weight heparin for the treatment of acute venous thromboembolism was performed. A literature search was performed using Advanced Pub Med and the Cochrane library database, and abstracts from recent meetings were reviewed. Two investigators extracted data independently. Results. Five studies, involving 1522 patients, were eligible. There were no statistically significant differences in the frequencies of symptomatic (odds ratio, 0.85 in favor of once-daily therapy at three months, p = 0.6), and asymptomatic, recurrent venous thromboembolism; total and major bleeds (odds ratio, 1.16 in favor of twice-daily therapy at 10 days, p = 0.8); and death, at 10 days, as well as at three months of follow-up. Conclusion. Once- daily low molecular weight heparin appears to be as effective and safe as twice-daily administration for the acute treatment of venous thromboembolism. However, there is inadequate data from studies that directly compared once-daily and twice-daily administration to be able to exclude the possibility of a higher frequency of fatal bleeding with once-daily therapy.

scholarly journals Efficacy and safety of anticoagulants for postoperative thrombophylaxis in total hip and knee arthroplasty: A PRISMA-compliant Bayesian network meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0250096
Author(s):  
Tailai He ◽  
Fei Han ◽  
Jiahao Wang ◽  
Yihe Hu ◽  
Jianxi Zhu
Keyword(s):  
Molecular Weight ◽  
Bayesian Network ◽  
Odds Ratio ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Low Molecular Weight ◽  
Significant Heterogeneity ◽  
Efficacy And Safety ◽  
Anticoagulant Drugs

Objective To search, review, and analyze the efficacy and safety of various anticoagulants from randomized clinical trials (RCTs) of anticoagulants for THA and TKA. Design PRISMA-compliant Bayesian Network Meta-analysis. Data sources and study selection The databases of The Medline, Embase, ClinicalTrial, and Cochrane Library databases were searched until March 2017 for RCTs of patients undergoing a THA or TKA. Main outcomes and measures The primary efficacy measurement was the venous thromboembolism Odds ratio (OR). The safety measurement was the odds ratio of major or clinically relevant bleeding. OR with 95% credibility intervals (95%CrIs) were calculated. Findings were interpreted as associations when the 95%CrIs excluded the null value. Results Thirty-five RCTs (53787 patients; mean age range, mostly 55–70 years; mean weight range, mostly 55–90 kg; and a higher mean proportion of women than men, around 60%) included the following Anticoagulants categories: fondaparinux, edoxaban, rivaroxaban, apixaban, dabigatran, low-molecular-weight heparin, ximelagatran, aspirin, warfarin. Anticoagulants were ranked for effectiveness as follows: fondaparinux (88.89% ± 10.90%), edoxaban (85.87% ± 13.34%), rivaroxaban (86.08% ± 10.23%), apixaban (68.26% ± 10.82%), dabigatran (41.63% ± 12.26%), low-molecular-weight heparin (41.03% ± 9.60%), ximelagatran (37.81% ± 15.87%), aspirin (35.62% ± 20.60%), warfarin (9.89% ± 9.07%), and placebo (4.56% ± 6.37%). Ranking based on clinically relevant bleeding events was as follows: fondaparinux (14.53% ± 15.25%), ximelagatran (18.93% ± 17.49%), rivaroxaban (23.86% ± 15.14%), dabigatran (28.30% ± 14.18%), edoxaban (38.76% ± 24.25%), low-molecular-weight heparin (53.28% ± 8.40%), apixaban (71.81% ± 10.92%), placebo (76.26% ± 14.61%), aspirin (86.32% ± 25.74%), and warfarin (87.95% ± 11.27%). No statistically significant heterogeneity was observed between trials. Conclusions and relevance According to our results, all anticoagulant drugs showed some effectiveness for VTE prophylaxis. Our ranking indicated that fondaparinux and rivaroxaban were safer and more effective than other anticoagulant drugs for patients undergoing THA or TKA.

Thromboprophylaxis in medical patients: the role of low-molecular-weight heparin

2004 ◽  
Vol 92 (07) ◽  
pp. 3-12 ◽  
Author(s):  
Timothy Norris ◽  
Turpie Alexander
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Medical Patients ◽  
Once Daily ◽  
Vte Prophylaxis ◽  
Increased Risk ◽  
Consensus Statements

SummaryMany hospitalised medical patients are at increased risk of venous thromboembolism (VTE). Consensus statements recommend that such patients be assessed for risk of VTE on admission to hospital and receive thromboprophylaxis where appropriate. However, VTE prophylaxis is not widely used in medical patients. One explanation is that assessing medical patients’ risk of VTE is complicated. The risk depends not only on the current illness but also on multiple intrinsic factors, and a variety of strategies for identifying patients who should receive thromboprophylaxis have been suggested. Thromboprophylaxis with unfractionated heparin (UFH) has proved to be effective in reducing the incidence of deep-vein thrombosis and overall mortality in medical patients. Clinical trial evidence, including a meta-analysis, suggests that thromboprophylaxis with low-molecular-weight heparin (LMWH) is at least as effective as with UFH, and also has the advantage of fewer bleeding complications. In particular, two large, randomised clinical trials – Prophylaxis in Medical Patients with Enoxaparin (MEDENOX) and Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients Trial (PREVENT) – showed that thromboprophylaxis with the LMWHs enoxaparin (40 mg s.c. once daily) or dalteparin (5,000 IU once daily) is more effective than placebo and well tolerated in medical patients. In addition, the Thromboembolism-Prevention in Cardiopulmonary Diseases with Enoxaparin (THE-PRINCE) trial showed that enoxaparin treatment was as effective as UFH. These studies provide solid evidence for the widespread use of thromboprophylaxis in medical patients.

Comparison between Fondaparinux and Low-Molecular-Weight Heparin in Patients with Acute Coronary Syndrome: A Meta-Analysis

Cardiology ◽  
2015 ◽  
Vol 133 (3) ◽  
pp. 163-172 ◽  
Author(s):  
Jianzhong Qiao ◽  
Xinlin Zhang ◽  
Jingmei Zhang ◽  
Peiwen Li ◽  
Biao Xu ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Acute Coronary Syndrome ◽  
Major Bleeding ◽  
Observational Studies ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Low Molecular Weight ◽  
Cardiac Events ◽  
Coronary Syndrome ◽  
Recurrent Ischemia

Objective: A number of studies have evaluated the efficacy and safety of fondaparinux versus low-molecular-weight heparin (LMWH) in patients with acute coronary syndrome (ACS), but the findings were not consistent across these studies. Methods: Electronic databases and article references were searched for studies that assessed fondaparinux versus LMWH in ACS patients. Results: Six studies met the inclusion criteria. There was a lower risk of major adverse cardiac events (MACE) with fondaparinux-based regimens both in randomized controlled trials (RCT; risk ratio, RR: 0.91, p = 0.04) and observational studies (RR: 0.85, p < 0.0001). Mortality decreased in fondaparinux-treated patients in RCT (RR: 0.84, p = 0.02), but not in observational studies (RR: 1.44, p = 0.64). For the analysis of myocardial infarction (MI), recurrent ischemia and stroke, none of the studies showed significant results. In addition, fondaparinux lowered the risk of major bleeding in RCT (RR: 0.62, p < 0.0001) and observational studies (RR: 0.65, p < 0.0001). The net clinical outcome also favored fondaparinux over LMWH in RCT (RR: 0.82, p < 0.0001) and observational studies (RR: 0.84, p < 0.0001). Conclusions: Among ACS patients, a fondaparinux-based regimen presented advantages regarding MACE and major bleeding, and a net clinical benefit compared with LMWH, although the benefit is minimal regarding MACE. For death, MI, recurrent ischemia and stroke, fondaparinux has not shown significant benefits.

Low-molecular-weight heparin for venous thromboprophylaxis in ambulatory cancer patients: A meta-analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9537-9537
Author(s):  
N. M. Kuderer ◽  
A. A. Khorana ◽  
C. W. Francis ◽  
G. H. Lyman ◽  
A. Falanga ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Relative Risk ◽  
Risk Reduction ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Low Molecular Weight ◽  
Vte Prophylaxis

9537 Background: Patients with cancer have an increased risk of venous thromboembolism (VTE). However, routine VTE prophylaxis is generally not recommended in ambulatory cancer patients. Several randomized controlled trials (RCTs) of low-molecular-weight heparin (LMWH) in ambulatory cancer patients have been reported with inconclusive results. Methods: A systematic review of RCTs of LMWH in ambulatory cancer patients without a VTE diagnosis was conducted. Included trials had to report VTE as primary or secondary outcome. An extensive electronic database search was conducted, including Medline, EMBASE, Cochrane Library along with abstracts from major meetings. Dual-blinded data extraction was performed. Meta-analysis was conducted using Mantel and Haenszel method to estimate relative risk (RR) and absolute risk difference (ARD) ± 95% CI. Primary outcomes in this analysis were all reported VTE and major bleeds. Most trials did not require VTE screening by imaging, precluding a separate analysis of asymptomatic VTE events. Results: Six RCTs were identified with a total of 2,648 patients including 1,525 receiving LMWH and 1,123 controls. No significant heterogeneity was observed across trials. Among patients receiving LMWH, the crude incidence of VTE was 2.95% compared to 5.25% among control patients. LMWH reduced the RR of VTE by 36% compared to controls (RR=0.64 [0.44 - 0.94], P=0.021), and reduced the ARD by 1.8% [0.2% - 3.4%]. Major bleeding events were reported in 1.57% LMWH patients compared to 0.98% in controls. The non-significant RR increase by LMWH for major bleeding was 1.85 [0.923 - 3.68], P=0.081, with an ARD of 0.9% [0.0% - 1.8%]. Results were comparable in the analysis limited to studies with VTE as primary outcome. Conclusions: While patients experienced a 36% relative risk reduction in VTE with LMWH, the absolute risk reduction was small, and concerns remain about the potential increase in major bleeding. Therefore, routine VTE prophylaxis in ambulatory cancer patients cannot be recommended at this time. Additional research is needed to identify cancer outpatients at high risk for VTE, in whom prophylaxis may have a more favorable risk-benefit ratio. [Table: see text]

“direct Oral Anticoagulants Versus Low-molecular-weight Heparin for Acute Treatment of Venous Thromboembolism in Patients With Gastrointestinal Cancer: a Systematic Review and Meta-analysis”

2021 ◽  
Author(s):  
Tarinee Rungjirajittranon ◽  
Weerapat Owattanapanich ◽  
Yingyong Chinthammitr ◽  
Theera Ruchutrakool ◽  
Bundarika Suwanawiboon
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Gi Cancer ◽  
Cancer Associated Thrombosis

Abstract BackgroundThe association between gastrointestinal (GI) cancer and a high incidence of venous thromboembolism (VTE) is well known. Previous randomized controlled studies demonstrated that direct oral anticoagulants (DOACs) effectively treat cancer-associated VTE (CAT). However, some DOACs appeared to increase the risk of bleeding, particularly in patients with GI malignancies. Therefore, the current systematic review and meta-analysis was conducted to evaluate the safety and efficacy of DOACs in GI cancer-associated thrombosis.MethodsAll relevant studies that compared DOACs and low-molecular-weight heparin (LMWH) in GI cancer-associated thrombosis that were published before December 2020 were individually searched in two databases (MEDLINE and EMBASE) by two investigators. The effect estimates and 95% confidence intervals (CI) from each eligible study were combined using the Mantel-Haenszel method.ResultsA total of 1,418 patients were included in this meta-analysis. The rate of major bleeding was not significantly different between groups (relative risk [RR]: 1.57, 95% CI: 0.93-2.65, P=0.09, I2=34%). However, the rate of clinically relevant non-major bleeding (CRNMB) was significantly higher in the DOACs group (RR: 1.98, 95% CI: 1.34-2.91, P=0.0005, I2=0%). The risk of recurrent VTE was not significantly different between groups (RR: 0.72, 95% CI: 0.41-1.28, P=0.27, I2=0%).ConclusionsThe current data suggests that treatment of GI cancer-associated thrombosis with DOACs significantly increases the risk of CRNMB, and a trend towards major bleeding risk in DOACs group. The efficacy of DOACs for preventing recurrent VTE in GI cancer was comparable to that of LMWHs.Trial registration: INPLASY202180113

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