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.

scholarly journals PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT): a randomised pragmatic trial protocol comparing aspirin versus low-molecular-weight heparin for blood clot prevention in orthopaedic trauma patients

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e041845
Author(s):  
Robert V O'Toole ◽  
Deborah M Stein ◽  
Katherine P Frey ◽  
Nathan N O'Hara ◽  
Daniel O Scharfstein ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Pragmatic Trial ◽  
Bleeding Complications ◽  
Wound Complications ◽  
Low Molecular Weight ◽  
Trauma Patients ◽  
Orthopaedic Trauma ◽  
Vte Prophylaxis ◽  
Increased Risk

Introduction Patients who sustain orthopaedic trauma are at an increased risk of venous thromboembolism (VTE), including fatal pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin (LMWH) for VTE prophylaxis in orthopaedic trauma patients. However, emerging literature in total joint arthroplasty patients suggests the potential clinical benefits of VTE prophylaxis with aspirin. The primary aim of this trial is to compare aspirin with LMWH as a thromboprophylaxis in fracture patients. Methods and analysis PREVENT CLOT is a multicentre, randomised, pragmatic trial that aims to enrol 12 200 adult patients admitted to 1 of 21 participating centres with an operative extremity fracture, or any pelvis or acetabular fracture. The primary outcome is all-cause mortality. We will evaluate non-inferiority by testing whether the intention-to-treat difference in the probability of dying within 90 days of randomisation between aspirin and LMWH is less than our non-inferiority margin of 0.75%. Secondary efficacy outcomes include cause-specific mortality, non-fatal PE and deep vein thrombosis. Safety outcomes include bleeding complications, wound complications and deep surgical site infections. Ethics and dissemination The PREVENT CLOT trial has been approved by the ethics board at the coordinating centre (Johns Hopkins Bloomberg School of Public Health) and all participating sites. Recruitment began in April 2017 and will continue through 2021. As both study medications are currently in clinical use for VTE prophylaxis for orthopaedic trauma patients, the findings of this trial can be easily adopted into clinical practice. The results of this large, patient-centred pragmatic trial will help guide treatment choices to prevent VTE in fracture patients. Trial registration number NCT02984384.

PS-100 Venous thromboembolism (VTE) prophylaxis for hospitalised medical patients (HMP) with low molecular weight heparin (LMWH)

2015 ◽  
Vol 22 (Suppl 1) ◽  
pp. A176.1-A176
Author(s):  
FI Ferreira Tátá ◽  
MA Pires Rebelo ◽  
ML Grenho Pereira ◽  
NM Ribeiro Landeira ◽  
SM Dias Fanica ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Medical Patients ◽  
Vte Prophylaxis

A Meta-Analysis to Determine the Risk of Heparin Induced Thrombocytopenia (HIT) and Isolated Thrombocytopenia in Prophylaxis Studies Comparing Unfractioneted Heparin (UFH) and Low Molecular Weight Heparin (LMWH).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2587-2587 ◽  
Author(s):  
Nadine Martel ◽  
Philip S. Wells
Keyword(s):  
Molecular Weight ◽  
Odds Ratio ◽  
Low Molecular Weight Heparin ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Low Molecular Weight ◽  
Medical Patients ◽  
Heparin Induced Thrombocytopenia ◽  
Significant Difference

Abstract HIT is an uncommon but potentially devastating complication of anticoagulation with UFH or LMWH. The absolute risk of HIT and thrombocytopenia are not clearly defined and no summary data to provide odds ratio is available. We conducted a meta-analysis to determine and compare the incidences of HIT in surgical or medical patients receiving thromboprophylaxis with either UFH or LMWH. We searched MEDLINE-OVID and MEDLINE-PubMed using and combining the following terms: heparin induced thrombocytopenia, low molecular weight heparin, prophylaxis, randomized controlled trials, prospective studies. The function Explode was used. Search was limited to humans from 1984 to 2004. Over 400 abstracts were reviewed and then 91 articles were independently reviewed by two authors, without any restriction of article language. Included studies were those comparing prophylactic UFH and LMWH and measuring HIT (defined as platelets drop > 50% or < 100 X 109/L AND positive laboratory HIT assay) or thrombocytopenia (defined as platelets drop > 50% or < 100 X 109/L) as outcomes. Studies defining thrombocytopenia with lower thresholds were excluded because cases could have been missed. Extracted data included patient characteristics, drug regimens, HIT, thrombocytopenia and venous thromboembolism rates. Disagreements were resolved by consensus. Eligible studies were included into the meta-analysis using a random-effects model to determine the odds ratio for the incidences of HIT and thrombocytopenia between UFH and LMWH. Funnel plots were made to assess possible publication bias. 17 articles were eligible with a total of 8500 patients: 2 RCTs measuring HIT; 10 RCTs measuring thrombocytopenia, and 5 prospective non-randomized studies with comparison groups measuring HIT. Three analysis were performed and all favoured the use of LMWH: 1) 2 RCTs measuring HIT showed an OR of 0.10 (95% confidence interval [CI] 0.01–0.77; p=0.03); 2) all 7 studies measuring HIT showed an OR of 0.11 (95%CI= 0.05–0.26; p< 0.00001); 3) 12 RCTs measuring thrombocytopenia showed an OR of 0.45 (95% CI= 0.26–0.80; p=0.006). Comparing the rates in the 7 studies measuring HIT UFH resulted in HIT in 3.4% (95%CI=2.6% to 4.3%) of cases and LMWH resulted in HIT in 0.2% (95% CI=0.1% to 0.6%), a statistically significant difference (p<0.0001). This meta-analysis confirms the lower incidences of HIT and thrombocytopenia with LMWH prophylaxis compared to UFH. Absolute rates of HIT with LMWH are very low. The HIT rates should be considered when determining the drug of choice for thromboprophylaxis in surgical and medical patients.

Antithrombotic drugs in acutely ill medical patients: review and meta-analysis of interventional trials with low-molecular-weight heparin and fondaparinux

2013 ◽  
Vol 10 (5) ◽  
pp. 615-627 ◽  
Author(s):  
Lorenzo Loffredo ◽  
Ludovica Perri ◽  
Elisa Catasca ◽  
Maria Del Ben ◽  
Francesco Angelico ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Low Molecular Weight ◽  
Medical Patients ◽  
Antithrombotic Drugs

Anti-Xa Potentiating Effect Of Low Molecular Weight Heparin

1981 ◽  
Author(s):  
W Junker ◽  
J Harenberg ◽  
F Fussi ◽  
K Mattes ◽  
R Zimmermann ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Intestinal Mucosa ◽  
Low Molecular Weight Heparin ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Clotting Time ◽  
Blood Samples ◽  
Increased Risk

Recently special attention has been drawn to bleeding complications of commercial heparins in patients with increased risk for haemorrhages. Alternative heparin preparations with high antithrombotic and low haemostaseological properties have been developed. We now report on a new low molecular weight (LMW) heaprin (mean MW 5000, 85 USP/mg), which has been obtained by depolymerisation of a heparin from pig intestinal mucosa (mean MW 15000, 154 USP/mg).In vitro the anti-Xa-activity (chromogenic substrate S2222) was 15% higher for the LMW heparin in a range of 0.01-2.0 USP/ml plasma. No difference was seen on the anti-IIa-activity (thrombin clotting time)and the aPTT for both heparins in the same range. Both Heparins were injected s.c. in a dose of 100, 50 and 25 USP/kg bodyweight into each of six volunteers randomly at weekly intervalIs. The pharmacodynamic effects were controlled for 6-10 hrs by 8-12 blood samples in relation to the dose applied. Increasing dosis the effects of each heparin increased in all test systems. The anti- Xa-activity of LMW heparin was somewhat higher at 100 and 25 USP/kg. At 50 USP/kg the effect of LMW heaprin was in the same range as 100 USP/kg of the original preparation (MW 15000). The factor Ila activity and aPTT were not influenced differently by the two heparins at each dose.The data indicate, that the LMW heparin presented here may have a more pronounced antithrombotic property by a specific anti-Xa-activity than the compaired commercial heparin. This effect is most pronounced at doses, which have only small haemostaseological effects.

scholarly journals Puncture site bleeding complications in patients with Clopidogrel hyper-response

2020 ◽  
pp. 58-65
Author(s):  
Nedeljković Žarko ◽  
Vukasinović Ivan ◽  
Majstorović Branisalva ◽  
Milosević Medenica Svetlana ◽  
Milićević Mihailo ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Antiplatelet Therapy ◽  
Femoral Artery ◽  
Low Molecular Weight Heparin ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Increased Risk

Dual antiplatelet therapy (clopidogrel and acetylsalicylic acid) is a standard for the embolization of planned intracranial aneurysms with CNS stent due to the possibility of stent thrombus formation. All anti-aggregation drugs, including those listed, have bleeding as a side effect. Three patients with aneurysm had an elevated response to antiplatelet therapy with clopidogrel, which was confirmed by a multiplate test on the "VerifyNow" system. After reducing the dose of clopidogrel or after interrupting it, with the introduction of low molecular weight heparin for the duration of five days, aneurysms were successfully resolved by intracranial implantation of the stent. Perioperative angiograms and postoperative CT angiograms have verified hematomas at the place of punction of the femoral artery. Bleeding was resolved by the femoral artery suture by a vascular surgeon. All patients were discharged home without further complications and with dual antiplatelet therapy. By measuring the platelet function in vitro, the degree of inhibition of platelet activity achieved by the action of the drug can be assessed. A specific test can identify those patients who are highly responsive to the drug with increased platelet reactivity and the possibility of increased risk of bleeding. Our suggestion is to reduce the dosage of clopidogrel or to leave it out for 24 hours with preventive doses of low molecular weight heparin or to change the strategy of treatment of intracranial aneurysm, i.e. avoiding implantation of CNS stent.

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.

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.

SAFE DOSING OF LMW HEPARIN IN HIP SURGERY

1987 ◽  
Author(s):  
U Hedner ◽  
T Mätzsch ◽  
D Berggvist ◽  
H Fredin ◽  
P Østergaard
Keyword(s):  
Molecular Weight ◽  
Plasma Levels ◽  
Low Molecular Weight Heparin ◽  
Hip Surgery ◽  
Bleeding Complications ◽  
Postoperative Blood Loss ◽  
Low Molecular Weight ◽  
Once Daily ◽  
Number Of Patients ◽  
Antithrombotic Efficacy

An enzymatically degraded low molecular weight heparin (mean mol wt 4900 dalton, LOGIPARIN, NOVO In-dustri, Denmark) was given s.c. in a dose of 35 Xal u/kg b.w. once daily to 10 patients undergoing elective hip surgery in order to study the plasma levels of Xal and Hal activity and with special regard to safety. The Xal activity in plasma was ≤ 0.24 Xal u/ml and the Hal activity ≤ 0.043 Hal u/ml. No bleeding complications were observed, and no increase in per- and postoperative blood loss was seen in the present study. It is therefore postulated that plasma levels of the Xal and Hal activities within the range obtained are safe with regard to bleeding complications for the LMW heparin used and in the dose administered. No accumulation was seen, which may contribute to the safety. No phlebographically verified thrombi were registered but the antithrombotic efficacy of the dose regimen used remains to be demonstrated in a larger number of patients under controlled conditions, a study that is well under way.

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.

Sign in / Sign up

Export Citation Format

Share Document