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The Journal of Thoracic and... Dec 2022The optimal duration of thromboprophylaxis in patients undergoing resection of primary lung cancer is not known. We investigated the incidence of pulmonary emboli and... (Review)
Review
OBJECTIVE
The optimal duration of thromboprophylaxis in patients undergoing resection of primary lung cancer is not known. We investigated the incidence of pulmonary emboli and venous thromboembolism in patients undergoing early-stage lung cancer resection and the impact of change from short duration to extended thromboprophylaxis.
METHODS
We reviewed the outcomes of consecutive patients who underwent resection of early-stage primary lung cancer following a change in protocol from inpatient-only to extended thromboprophylaxis to 28 days. Propensity-score matching of control (routine inpatient pharmacologic thromboprophylaxis) and treatment group (extended pharmacologic thromboprophylaxis) was performed. Adjustment for covariates based on the Caprini risk assessment model was undertaken. Thromboembolic outcomes were compared between the 2 groups.
RESULTS
Seven hundred fifty consecutive patients underwent resection of primary lung cancer at Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018. Six hundred patients were included for analysis and propensity-score matching resulted in 253 matched pairs. Extended prophylaxis was associated with a significant reduction in pulmonary emboli (10 of 253 patients [4%] vs 1 of 253 patients [0.4%], P = .01). One patient (0.4%) developed a bleeding complication within the treatment cohort. Multivariable logistic regression model demonstrated that extended thromboprophylaxis was independently associated with a reduction in postoperative pulmonary emboli.
CONCLUSIONS
Patients undergoing lung cancer resection surgery are at moderate-to-high risk of postoperative thromboembolic disease. Extended dalteparin for 28 days is safe and is associated with reduced incidence of pulmonary embolus in patients undergoing resection of early-stage primary lung cancer.
Topics: Humans; Venous Thromboembolism; Anticoagulants; Drug Administration Schedule; Pulmonary Embolism; Postoperative Complications; Lung Neoplasms
PubMed: 35953309
DOI: 10.1016/j.jtcvs.2022.06.016 -
TH Open : Companion Journal To... Jan 2023Thrombocytopenia is common among critically ill sepsis patients, while they also hold an increased risk for thromboembolic events. Thus, the choice of anticoagulant...
Thrombocytopenia is common among critically ill sepsis patients, while they also hold an increased risk for thromboembolic events. Thus, the choice of anticoagulant prophylaxis for this patient population is challenging. We investigated the effect of low-molecular-weight heparin (dalteparin) and direct thrombin inhibitor (argatroban) on the hemostasis in blood from sepsis patients with new-onset thrombocytopenia. Thrombocytopenia was defined as a platelet count drop of ≥30% and/or from >100 × 10 /L to 30 to 100 × 10 /L within 24 hours prior to inclusion. We included five healthy individuals and ten patients. Analyses of thrombin generation (Calibrated Automated Thrombogram), thrombin-antithrombin (TAT) complex levels, prothrombin fragment 1+2 (F1+2), and rotational thromboelastometry (ROTEM) were performed. Based on dose-response relationships investigated in healthy blood, patient samples were spiked with prophylactic (0.25 IU/mL) and therapeutic (0.75 IU/mL) dalteparin and low (0.25 µg/mL) and high (0.50 µg/mL) argatroban concentrations, each with a sample without anticoagulant. In patients, the endogenous thrombin potential was markedly lower in therapeutic dalteparin samples than in samples without anticoagulant [median (range): 29 (0-388) vs. 795 (98-2121) nM × min]. In high argatroban concentration samples, thrombin lag time was longer than in samples without anticoagulant [median (range): 15.5 (10.5-20.2) versus 5.3 (2.8-7.3) min]. Dalteparin and argatroban both increased clotting time but did not affect maximum clot firmness in the ROTEM INTEM assay. Six patients had elevated TAT and eight patients had elevated F1 + 2. In conclusion, dalteparin mainly affected the amount of thrombin generated and argatroban delayed clot initiation in critically ill sepsis patients with new-onset thrombocytopenia. Neither anticoagulant affected clot strength.
PubMed: 36751302
DOI: 10.1055/a-2000-6576 -
Journal of the American College of... Feb 2003A substantial number of clinical studies have consistently demonstrated that low-molecular-weight heparin (LMWH) compounds are effective and safe alternative... (Review)
Review
A substantial number of clinical studies have consistently demonstrated that low-molecular-weight heparin (LMWH) compounds are effective and safe alternative anticoagulants to unfractionated heparins (UFHs). They have been found to improve clinical outcomes in acute coronary syndromes and to provide a more predictable therapeutic response, longer and more stable anticoagulation, and a lower incidence of UFH-induced thrombocytopenia. Of the several LMWH agents that have been studied in large clinical trials, including enoxaparin, dalteparin, and nadroparin, not all have shown better efficacy than UFH. Enoxaparin is the only LMWH compound to have demonstrated sustained clinical and economic benefits in comparison with UFH in the management of unstable angina/ non-ST-segment elevation myocardial infarction (NSTEMI). Also, LMWH appears to be a reliable and effective antithrombotic treatment as adjunctive therapy in patients undergoing percutaneous coronary intervention. Clinical trials with enoxaparin indicate that LMWH is effective and safe in this indication, with or without the addition of a glycoprotein IIb/IIIa inhibitor. The efficacy demonstrated by enoxaparin in improving clinical outcomes in unstable angina/NSTEMI patients has led to investigations of its role in the management of ST-segment elevation myocardial infarction. Initial results are very encouraging, and they indicate that enoxaparin may potentially substitute for UFH as adjunctive therapy in fibrin-specific thrombolytic regimens and improve coronary reperfusion rates in streptokinase-based regimens.
Topics: Acute Disease; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Blood Coagulation Factors; Enoxaparin; Humans; Myocardial Infarction; Outcome Assessment, Health Care
PubMed: 12644342
DOI: 10.1016/s0735-1097(02)02901-7 -
Effects of dalteparin on anti-Xa activities cannot be predicted in critically ill COVID-19 patients.British Journal of Clinical Pharmacology Jun 2022Critically ill COVID-19 patients are at high risk of thromboembolic events despite routine-dosed low-molecular-weight heparin thromboprophylaxis. However, in recent...
Critically ill COVID-19 patients are at high risk of thromboembolic events despite routine-dosed low-molecular-weight heparin thromboprophylaxis. However, in recent randomized trials increased-intensity thromboprophylaxis seemed futile and possibly even harmful. In this explorative pharmacokinetic (PK) study we measured anti-Xa activities on frequent timepoints in 15 critically ill COVID-19 patients receiving dalteparin and performed PK analysis by nonlinear mixed-effect modelling. A linear one-compartment model with first-order kinetics provided a good fit. However, wide interindividual variation in dalteparin absorption (variance 78%) and clearance (variance 34%) was observed, unexplained by routine clinical covariates. Using the final PK model for Monte Carlo simulations, we predicted increased-intensity dalteparin to result in anti-Xa activities well over prophylactic targets (0.2-0.4 IU/mL) in the majority of patients. Therapeutic-intensity dalteparin results in supratherapeutic anti-Xa levels (target 0.6-1.0 IU/mL) in 19% of patients and subtherapeutic levels in 22%. Therefore, anti-Xa measurements should guide high-intensity dalteparin in critically ill COVID-19 patients.
Topics: Anticoagulants; Critical Illness; Dalteparin; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Venous Thromboembolism; COVID-19 Drug Treatment
PubMed: 34965610
DOI: 10.1111/bcp.15208 -
Medicinski Glasnik : Official... Feb 2023Aim To determine differences between reviparin and dalteparin treatment in patients with extracapsular hip fractures treated with intramedullary nailing and their...
Comparative analysis of the effects of dalteparin and reviparin on perioperative blood loss in patients with extracapsular hip fractures treated with intramedullary nailing.
Aim To determine differences between reviparin and dalteparin treatment in patients with extracapsular hip fractures treated with intramedullary nailing and their effects on perioperative blood loss and early postoperative recovery. Methods Retrospective comparative study included 68 patients with extracapsular hip fracture who were divided into dalteparin and reviparin group. Medical records were used to obtain demographic data, laboratory parameters, haemoglobin and haematocrit levels, platelet count, mortality rate and medical complications. Results Out of total 68 patients, 31 were in reviparin and 37 in dalteparin group. Mean age of patients was 70.5 (±14.4) and 76.8 (±8.4) years in reviparin and dalteparin group, respectively (p=0.071). Median values of haemoglobin levels on the first postoperative day were lower in dalteparin group compared to reviparin group (p=0.012). On the first postoperative day haematocrit values were also lower in dalteparin than in reviparin group (p=0.015). Both groups showed an increase in platelet count on the first postoperative day, but without significant difference (p=0.084). There was no statistically significant difference in intrahospital mortality between the groups (6.4% vs. 2.7%; p=0.588). One case of pulmonary embolism was detected in the dalteparin group. Conclusion Low-molecular-weight heparin is the drug of choice in patients with hip fractures for thromboprophylaxis. Due to non-antithrombin-mediated actions, reviparin and dalteparin could have different effects on perioperative blood loss. Both dalteparin and reviparin are safe and effective agents for thromboprophylaxis in patients with proximal femur fractures.
PubMed: 36435999
DOI: 10.17392/1526-22 -
Journal of Thrombosis and Haemostasis :... Nov 2021Clinical guidelines advise similar anticoagulant treatment for symptomatic and incidental cancer-associated venous thromboembolism (VTE). We investigated clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Clinical guidelines advise similar anticoagulant treatment for symptomatic and incidental cancer-associated venous thromboembolism (VTE). We investigated clinical features and outcomes of cancer patients with incidental or symptomatic VTE randomized in the Caravaggio study.
OBJECTIVES
We performed a predefined sub-analysis of the Caravaggio study in order to investigate the clinical features and outcomes of incidental and symptomatic VTE in patients with cancer. The relative efficacy and safety of apixaban and dalteparin in patients with incidental and symptomatic VTE was also assessed.
METHODS
The Caravaggio study compared apixaban to dalteparin for the 6-month treatment of cancer-associated VTE. The primary efficacy and safety outcomes were recurrent VTE and major bleeding.
RESULTS
Two hundred thirty patients (20%) had incidental and 925 (80%) symptomatic VTE. Pulmonary embolism with or without deep vein thrombosis as index event, colorectal cancer, Eastern Cooperative Oncology Group (ECOG) score of 0, and locally advanced or metastatic cancer were more frequent in patients with incidental VTE. Deep vein thrombosis as index event, hematological cancer, and ECOG score of 2 were more frequent in patients with symptomatic VTE. Ten patients (4.3%) with incidental and 68 (7.4%) with symptomatic VTE had recurrent VTE (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.29-1.10). Major bleeding occurred in 12 (5.2%) patients with incidental VTE and in 33 (3.6%) patients with symptomatic VTE (HR 1.43, 95% CI 0.74-2.77). When comparing apixaban to dalteparin in patients with symptomatic and incidental VTE, the HR for recurrence was 0.73 (95% CI 0.45-1.19) and 0.41 (95% CI 0.11-1.56), respectively, and the HR for major bleeding 0.93 (95% CI 0.47-1.83) and 0.96 (95% CI 0.31-2.96), respectively.
CONCLUSIONS
Compared to cancer patients with symptomatic VTE, those with incidental VTE have different clinical features at presentation, with a numerically lower incidence of recurrent VTE and a numerically higher incidence of major bleeding.
Topics: Anticoagulants; Dalteparin; Hemorrhage; Humans; Neoplasm Recurrence, Local; Neoplasms; Venous Thromboembolism
PubMed: 34260816
DOI: 10.1111/jth.15461 -
Journal of Thrombosis and Haemostasis :... Nov 2014Low molecular weight heparins (LMWHs) constitute the mainstay of anticoagulant therapy for pediatric venous thromboembolism (VTE). The safety and effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Low molecular weight heparins (LMWHs) constitute the mainstay of anticoagulant therapy for pediatric venous thromboembolism (VTE). The safety and effectiveness of dalteparin, an LMWH, has not been established in children, and pediatric data on dalteparin for VTE are limited to one single-center experience.
OBJECTIVE
To establish dose-finding (primary endpoint) and efficacy/safety outcomes (secondary endpoints) in children treated with dalteparin in a substudy of the Kids-DOTT trial.
PATIENTS AND METHODS
A prospective multicenter trial using dalteparin subcutaneously twice daily for acute VTE in children aged ≤ 21 years was conducted under an investigator-held Investigational New Drug application registered with the US Food and Drug Administration. Initial weight-based dosing per protocol was as follows: infants (< 12 months), 150 IU kg(-1) ; children (1-12 years), 125 IU kg(-1) ; and adolescents (13-18 years), 100 IU kg(-1) . Bleeding events were categorized according to ISTH criteria. Descriptive non-parametric statistics were employed for all analyses.
RESULTS
Eighteen patients (67% male) were enrolled from January 2010 to October 2013 across four centers. No supratherapeutic levels were observed. Median (range) therapeutic doses by age group were as follows: infants (n = 3), 180 IU kg(-1) (146-181 IU kg(-1) ); children (n = 7), 125 IU kg(-1) (101-175 IU kg(-1) ); and adolescents (n = 8), 100 IU kg(-1) (91-163 IU kg(-1) ). The median duration of dalteparin use was 48 days (range: 2-169 days), and the median follow-up was 10.5 months (range: 2-35 months). There were no related serious adverse events, no clinically relevant bleeding events, and no symptomatic recurrent VTEs.
CONCLUSION
Dalteparin successfully achieved targeted anti-factor Xa levels in 18 children and young adults with acute VTE with a standardized age-based dosing regimen, with a favorable safety and efficacy profile.
Topics: Acute Disease; Adolescent; Age Factors; Anticoagulants; Child; Child, Preschool; Dalteparin; Drug Administration Schedule; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Injections, Subcutaneous; Male; Patient Safety; Pilot Projects; Prospective Studies; Recurrence; Risk Factors; Time Factors; Treatment Outcome; United States; Venous Thromboembolism
PubMed: 25182454
DOI: 10.1111/jth.12716 -
Texas Heart Institute Journal 2010In Part 1 of this review, we discussed how plaque rupture is the most common underlying cause of most cases of unstable angina/non-ST-segment-elevation myocardial... (Review)
Review
In Part 1 of this review, we discussed how plaque rupture is the most common underlying cause of most cases of unstable angina/non-ST-segment-elevation myocardial infarction (UA/NSTEMI) and how early risk stratification is vital for the timely diagnosis and treatment of acute coronary syndromes (ACS). Now, in Part 2, we focus on the medical therapies and treatment strategies (early conservative vs early invasive) used for UA/NSTEMI. We also discuss results from various large randomized controlled trials that have led to the contemporary standards of practice for, and reduced morbidity and death from, UA/NSTEMI. In summary, ACS involving UA/NSTEMI is associated with high rates of adverse cardiovascular events, despite recent therapeutic advances. Plaque composition and inflammation are more important in the pathogenesis of ACS than is the actual degree of arterial stenosis. As results from new trials challenge our current practices and help us develop the optimal treatment strategy for UA/NSTEMI patients, the cornerstones of contemporary treatment remain early risk stratification and aggressive medical therapy, supplemented by coronary angiography in appropriately selected patients. An early-invasive-treatment strategy is of most benefit to high-risk patients, whereas an early-conservative strategy is recommended for low-risk patients. Adjunctive medical therapy with acetylsalicylic acid, clopidogrel or another adenosine diphosphate antagonist, glycoprotein IIb/IIIa inhibitors, and either low-molecular-weight heparin or unfractionated heparin, in the appropriate setting, further reduces the risk of ischemic events secondary to thrombosis. Short- and long-term inhibition of platelet aggregation should be achieved by appropriately evaluating the risk of bleeding complications in these patients.
Topics: Acute Coronary Syndrome; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Artery Bypass; Evidence-Based Medicine; Hemorrhage; Humans; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 20548800
DOI: No ID Found -
BMJ Case Reports Mar 2017A young woman developed a line-associated deep vein thrombosis (DVT), which was treated with low molecular weight heparin (dalteparin). 8 days later, the DVT had...
A young woman developed a line-associated deep vein thrombosis (DVT), which was treated with low molecular weight heparin (dalteparin). 8 days later, the DVT had significantly extended-in spite of therapeutic heparin levels. A diagnosis of heparin-induced thrombocytopenia and thrombosis (HITT) was considered, but the platelet count had not dropped. Nevertheless, a HITT assay was carried out which came back positive, with a repeat assay confirming the result. Dalteparin was stopped and apixaban treatment started, with symptomatic recovery over the following days and weeks.
Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Platelet Count; Pyrazoles; Pyridones; Thrombocytopenia; Thrombosis; Venous Thrombosis
PubMed: 28314810
DOI: 10.1136/bcr-2016-218919 -
The Netherlands Journal of Medicine Dec 2019Monitoring low-molecular-weight heparins is generally not required. However, guidelines advise to monitor anti-Xa levels in patients with renal insufficiency or a BMI...
BACKGROUND
Monitoring low-molecular-weight heparins is generally not required. However, guidelines advise to monitor anti-Xa levels in patients with renal insufficiency or a BMI above 50, and in pregnancy. Measuring anti-Xa levels is a complex challenge since sampling should be performed three to five hours after subcutaneous injection and after steady state concentrations have been reached. Strict compliance is pivotal for justified dose adjustments.
OBJECTIVES
We questioned compliance to our protocol and performed this study to explore that.
METHODS
This retrospective cohort study included patients ≥ 18 years receiving therapeutic dalteparin in a Dutch academic medical centre. Patients with a first anti-Xa level measured between February 23rd and December 30th, 2017 were selected. According to our local guideline, monitoring anti-Xa activity is indicated in patients on therapeutic doses of dalteparin who are pregnant, morbidly obese (BMI > 50), or have renal insufficiency (clearance < 60 ml/min). Accurate sampling was defined as measuring levels after at least three injections (after which a patient may reach steady state) and then four hours after the injection with dalteparin. The frequency of compliance to our protocol was assessed.
RESULTS
We included 158 patients with 396 anti-Xa levels, of which 41% (65/158) of all first anti-Xa levels were drawn without appropriate indication. Almost half, 48% (211/396), were sampled incorrectly and 25% of these (53/211) were followed by a dose adjustment. In total, 74% (293/396) of the samples were not indicated or were taken at the wrong time.
CONCLUSIONS
Monitoring anti-Xa levels is a complex clinical challenge. This study showed that non-compliance with recommendations for anti-Xa monitoring was high, often resulting in unjustified dose adjustments.
Topics: Academic Medical Centers; Adult; Anticoagulants; Dalteparin; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Male; Medication Adherence; Middle Aged; Netherlands; Retrospective Studies; Venous Thromboembolism; Young Adult
PubMed: 31880268
DOI: No ID Found