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Haematologica Jun 2024Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to... (Randomized Controlled Trial)
Randomized Controlled Trial
Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to anticoagulants is limited. The HOKUSAI VTE Cancer study was a randomized, open-label, non-inferiority, phase III trial comparing dalteparin with edoxaban in CAT patients. This post hoc analysis of Hokusai VTE Cancer Study was performed to compare outcomes in patients with platelet count ≤100x109/L at one or more specified time points (baseline, 1-month, or 3-month) versus those without thrombocytopenia. Cumulative incidences at 180 days were calculated with death as a competing risk. The primary outcome was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis, and survival. The analysis included 1,045 patients with primarily solid tumor malignancies (89%), median age 65 years, and 52% male. The thrombocytopenia group comprised 9.6% (N=101) of the cohort and relative to the non-thrombocytopenia cohort (N=944), experienced significantly higher major bleeding (9.0% vs. 4.0%, sub-distribution hazard ratio [SHR] =2.4; P=0.02) and CRNMB (17.9% vs. 9.6%, SHR=2.0; P=0.01). Thrombocytopenia did not impact recurrent venous thromboembolic event (VTE) (9.8% vs. 7.4%, SHR=1.3; P=0.37) nor overall mortality (21.8% vs. 26.0%, HR=0.9; P=0.48). Major bleeding was higher in patients with thrombocytopenia and gastrointestinal malignancies receiving edoxaban versus dalteparin (16.8% vs. 0; P<0.01) but similar for patients with other malignancies (P=0.30). In patients with hematologic malignances and thrombocytopenia major bleeding was higher for patients receiving dalteparin compared to edoxaban (19.0% vs. 0; P<0.01). Mild thrombocytopenia was associated with a doubling in risk of major hemorrhage in patients receiving anticoagulation for CAT. Bleeding risk for edoxaban and dalteparin varied in gastrointestinal and hematologic malignances in patients with thrombocytopenia (clinicaltrails gov. Identifier: NCT02073682).
Topics: Humans; Male; Female; Thrombocytopenia; Aged; Neoplasms; Hemorrhage; Middle Aged; Thrombosis; Recurrence; Pyridines; Thiazoles; Anticoagulants; Dalteparin
PubMed: 37855029
DOI: 10.3324/haematol.2023.284192 -
American Journal of Hematology Sep 2023Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative...
Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative thromboprophylaxis in these patients. We conducted a population-based, retrospective cohort study among adults ≥66 years old with CKD undergoing hip or knee arthroplasty who had filled an outpatient prophylactic anticoagulant prescription between 2010 and 2020 in Ontario, Canada. The primary outcomes of venous thrombosis (VTE) and hemorrhage were identified by validated algorithms using relevant diagnoses and billing codes. Overlap-weighted cause-specific Cox proportional hazard models were used to examine the association of direct oral anticoagulants (DOAC) on the 90-day risk of VTE and hemorrhage compared with low-molecular-weight heparin (LMWH). A total of 27 645 patients were prescribed DOAC (N = 22 943) or LMWH (N = 4702) after arthroplasty. Rivaroxaban was the predominant DOAC (94.5%), while LMWH mainly included enoxaparin (67%) and dalteparin (31.5%). DOAC users had higher eGFRs, fewer co-morbidities, and surgery in more recent years compared to LMWH users. After weighing, DOAC (compared with LMWH) was associated with a lower risk of VTE (DOAC: 1.5% vs. LMWH: 2.1%, weighted hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59-0.94) and a higher risk of hemorrhage (DOAC: 1.3% vs. LMWH: 1.0%, weighted HR 1.44, 95% CI 1.04-1.99). Additional analyses including a more stringent VTE defining algorithm, different eGFR cut-offs, and limiting to rivaroxaban and enoxaparin showed consistent findings. Among elderly adults with CKD, DOAC was associated with a lower VTE risk and a higher hemorrhage risk compared to LMWH following hip or knee arthroplasty.
Topics: Adult; Humans; Aged; Anticoagulants; Venous Thromboembolism; Heparin, Low-Molecular-Weight; Enoxaparin; Rivaroxaban; Arthroplasty, Replacement, Knee; Retrospective Studies; Hemorrhage; Renal Insufficiency, Chronic; Ontario
PubMed: 37340812
DOI: 10.1002/ajh.26994 -
Blood Coagulation & Fibrinolysis : An... Apr 2024Venous thromboembolism (VTE) is a preventable cause of significant morbidity and mortality in hospitalized patients world-wide. In Australia, the low-molecular weight... (Observational Study)
Observational Study
Venous thromboembolism (VTE) is a preventable cause of significant morbidity and mortality in hospitalized patients world-wide. In Australia, the low-molecular weight heparins (LMWHs) enoxaparin or dalteparin are usually used as first-line prophylaxis for VTE, though there is uncertainty whether dalteparin has the same effectiveness as enoxaparin in real-world settings. This is relevant because dalteparin is less renally cleared and may be more cost effective than enoxaparin. The aim of this study was to explore VTE event incidence in a general cohort of hospitalized adult inpatients who were prescribed enoxaparin or dalteparin for VTE prophylaxis. A retrospective observational study was conducted at a quaternary hospital in Brisbane, Australia, of patients who had experienced a hospital-acquired VTE from 1 September 2021 to 1 March 2023. Patients were identified from routinely collected data following an in-hospital VTE event, and further data was retrieved retrospectively from the integrated electronic Medical Record (ieMR). Incidence and type of VTE events, LMWH-prescribing patterns, and risk factors were assessed. The incidence of VTE events were similar across the dalteparin and enoxaparin cohorts (42.1 events/10 000 patients vs. 34.4 events/10 000 patients, respectively), although patients prescribed enoxaparin had a higher number of risk factors, particularly obesity and active cancer. Our research indicates comparable incidence of VTE in patients prescribed dalteparin compared with enoxaparin in an Australian hospital general cohort of adult inpatients. Dalteparin may be as effective as enoxaparin for VTE prophylaxis in a real-world cohort of patients, and as such dalteparin may be considered a suitable alternative to enoxaparin for VTE prophylaxis. Further research including large randomized controlled trials are required to confirm these results.
Topics: Adult; Humans; Dalteparin; Enoxaparin; Venous Thromboembolism; Heparin, Low-Molecular-Weight; Retrospective Studies; Australia; Anticoagulants
PubMed: 38358899
DOI: 10.1097/MBC.0000000000001281 -
European Journal of Orthopaedic Surgery... Dec 2023The purpose of this study was to compare the effects of reviparin, dalteparin and enoxaparin on intraoperative blood loss in patients with trochanteric fracture treated...
PURPOSE
The purpose of this study was to compare the effects of reviparin, dalteparin and enoxaparin on intraoperative blood loss in patients with trochanteric fracture treated with intramedullary nailing.
MATERIALS AND METHODS
This retrospective multicenter study included 100 patients with trochanteric fracture who were divided into three groups according to the low-molecular-weight heparin administered. In all cases, a short third generation Gamma nail was used for osteosynthesis. Complete blood count and number of red blood cell transfusions (RBC) were evaluated.
RESULTS
The mean value of postoperative haemoglobin level was lower in the enoxaparin group compared to the reviparin group, with significant difference (p = 0.001; 95% CI 4.1-18.87). Patients in the dalteparin group received more RBC transfusions compared to the reviparin and enoxaparin group (p = 0.048).
CONCLUSION
The use of enoxaparin and dalteparin in hip fracture patients can result in lower postoperative haemoglobin levels and more RBC transfusions compared to reviparin.
Topics: Humans; Enoxaparin; Dalteparin; Anticoagulants; Fracture Fixation, Intramedullary; Heparin, Low-Molecular-Weight; Blood Loss, Surgical; Hip Fractures; Hemoglobins; Bone Nails
PubMed: 37256390
DOI: 10.1007/s00590-023-03608-9 -
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 -
Talanta Apr 2024This article presents a novel proof of concept for the blood plasma quantification of clinically relevant concentrations of direct oral anticoagulants, DOACs, including...
This article presents a novel proof of concept for the blood plasma quantification of clinically relevant concentrations of direct oral anticoagulants, DOACs, including rivaroxaban and edoxaban, as well as low-molecular-weight heparins, LMWHs, such as enoxaparin and dalteparin, utilising a calibration-free disposable electrochemical sensor with co-facing electrodes. A dose-response curve was generated for rivaroxaban and edoxaban to demonstrate the sensor's ability to detect ≥9.00 ng mL rivaroxaban and quantify it in the 11.0-140 ng mL range. Similarly, the lower detection limit for edoxaban was 12.9 ng mL, with a quantification range of 16.8-140 ng mL. The significance of this sensor lies in its ability to quantify rivaroxaban and edoxaban below 30 ng mL, which is crucial in emergency care centres when patients undergoing DOAC therapy require emergency surgery or reversal of DOACs due to bleeding or ischemic stroke. Furthermore, the sensor can detect ≥0.016 IU mL enoxaparin and ≥0.013 IU mL dalteparin and quantify them in the 0.025-0.75 and 0.019-0.75 IU mL range, respectively. Additionally, a dose-response curve was presented to demonstrate the potential ability of this sensor to quantify factor-Xa inhibitors independently of which DOACs or LMWHs are used. With the assay completed in less than 30 s using a minimal volume of 7 μL sample, the possibility to work at physiological pH and under calibration-free format makes this assay an excellent candidate for point-of-care testing.
Topics: Humans; Factor Xa Inhibitors; Rivaroxaban; Enoxaparin; Dalteparin; Point-of-Care Systems; Anticoagulants; Administration, Oral; Pyridines; Thiazoles
PubMed: 38159356
DOI: 10.1016/j.talanta.2023.125593 -
Journal of Orthopaedics Jul 2023Total knee arthroplasty is a common and effective procedure. Although complication rates are low, certain complications such as venous thromboembolism are potentially...
INTRODUCTION
Total knee arthroplasty is a common and effective procedure. Although complication rates are low, certain complications such as venous thromboembolism are potentially serious. The optimal prophylactic agent and dosage after revision knee arthroplasty remains unclear. The main objective of this work was to study the efficacy and safety of aspirin as a thromboprophylaxis agent following revision knee arthroplasties.
PATIENTS AND METHODS
A retrospective review of patients undergoing revision knee arthroplasty between 2013 and 2020at a University Teaching Hospital was undertaken. The primary outcome was the development of a symptomatic thromboembolic event requiring treatment within 90 days post-surgery. The secondary outcomes were adverse events associated with aspirin therapy: surgical site infection rate; incidence of major bleeding; readmission rate and mortality within 90 days post-surgery.
RESULTS
490 patients were included. 374 (76.3%) received prophylactic aspirin (150 mg once daily for 28 days) and 75 (15.3%) patients received dalteparin for 28 days due to contraindication to aspirin use. Those already receiving other thromboprophylaxis agents for pre-existing comorbidities continued these after relevant medical consultation. The overall rates of venous thromboembolism and symptomatic DVT after aspirin prophylaxis were 0.6% (3/490) and 0.8% (3/374), respectively. VTE incidence did not significantly differ between those administered aspirin and other agents. No patient experienced major bleeding within 90 postoperative days. Only 2 of 490 (0.4%) patients had wound infection requiring readmission; neither received prophylactic aspirin.
CONCLUSION
Extended out-of-hospital thromboembolic prophylaxis with aspirin may be at least as effective as other agents in patients undergoing revision knee arthroplasty. Aspirin is safe, effective, and cheap compared with other agents.
PubMed: 37275515
DOI: 10.1016/j.jor.2023.05.006 -
Pharmacoepidemiology and Drug Safety May 2024Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were... (Comparative Study)
Comparative Study
Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.
PURPOSE
Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer.
METHODS
A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results.
RESULTS
The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups.
CONCLUSIONS
The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.
Topics: Humans; Enoxaparin; Pulmonary Embolism; Venous Thrombosis; Risk Assessment; Neoplasms; Dalteparin; Tinzaparin; Heparin, Low-Molecular-Weight; Anticoagulants; Secondary Prevention; Hemorrhage; Adult
PubMed: 38680090
DOI: 10.1002/pds.5795 -
Medicina (Kaunas, Lithuania) Jan 2024There was an error in the original publication [...].
Correction: Arce-Huamani et al. Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis. 2023, , 1867.
There was an error in the original publication [...].
PubMed: 38256435
DOI: 10.3390/medicina60010134 -
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