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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 -
The Cochrane Database of Systematic... Dec 2021Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. (Review)
Review
BACKGROUND
Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE.
OBJECTIVES
To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer.
SEARCH METHODS
We performed a comprehensive search in the following major databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid). We also handsearched conference proceedings, checked references of included studies, and searched for ongoing studies. This update of the systematic review is based on the findings of a literature search conducted on 14 August 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE.
DATA COLLECTION AND ANALYSIS
Using a standardised form, we extracted data - in duplicate - on study design, participants, interventions, outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, symptomatic VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach.
MAIN RESULTS
Of 11,484 identified citations, 3073 were unique citations and 15 RCTs fulfilled the eligibility criteria, none of which were identified in the latest search. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH; one compared fondaparinux with UFH and LMWH; and one compared dalteparin with tinzaparin, two different types of low molecular weight heparin. The meta-analyses showed that LMWH may reduce mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; low certainty evidence) and may reduce VTE recurrence slightly (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; low certainty evidence). There were no data available for bleeding outcomes, postphlebitic syndrome, quality of life, or thrombocytopenia. The study comparing fondaparinux with heparin (UFH or LMWH) found that fondaparinux may increase mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; low certainty evidence), may result in little to no difference in recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; low certainty evidence), may result in little to no difference in major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; low certainty evidence), and probably increases minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence). There were no data available for postphlebitic syndrome, quality of life, or thrombocytopenia. The study comparing dalteparin with tinzaparin found that dalteparin may reduce mortality slightly (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), may reduce recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), may increase major bleeding slightly (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), and may reduce minor bleeding slightly (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence). There were no data available for postphlebitic syndrome, quality of life, or thrombocytopenia.
AUTHORS' CONCLUSIONS
Low molecular weight heparin (LMWH) is probably superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Venous Thromboembolism
PubMed: 34878173
DOI: 10.1002/14651858.CD006649.pub8 -
European Journal of Cancer (Oxford,... May 2021Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of concomitant administration of anticancer agents and apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism.
BACKGROUND
Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE) is undefined. The pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern.
METHODS
We evaluated the effects of concomitant administration of anticancer agents on recurrent VTE, major bleeding and death in patients with cancer-associated VTE randomised to receive apixaban or dalteparin in the Caravaggio study.
RESULTS
Anticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban, recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated with anticancer agents, respectively (hazard ratio [HR] = 1.14; 0.55-2.38); major bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34-1.82), and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71; 0.51-1.00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%) and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively (HR = 0.71; 0.40-1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients, respectively (HR = 1.78; 0.66-4.79), and death occurred in 87 (26.2%) and 66 (26.7%) patients, respectively (HR = 0.85; 0.62-1.18). The comparative efficacy and safety of apixaban and dalteparin was not different in patients treated or not treated with anticancer agents. No effect on recurrent VTE, major bleeding or death was observed with inhibitors or inducers of P-glycoprotein and/or CYP3A4.
CONCLUSION
In our study, concomitant administration of anticancer agents had no effect on the risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin for cancer-associated VTE.
Topics: Aged; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Dalteparin; Drug Therapy, Combination; Equivalence Trials as Topic; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Neoplasm Recurrence, Local; Neoplasms; Prognosis; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 33780665
DOI: 10.1016/j.ejca.2021.02.026 -
Deutsche Medizinische Wochenschrift... Jul 2020The present article addresses clinical challenges associated with the choice of the anticoagulant agent, the definition of the duration of anticoagulant treatment and...
The present article addresses clinical challenges associated with the choice of the anticoagulant agent, the definition of the duration of anticoagulant treatment and the assessment of the risk-to-benefit ratio of prolonged anticoagulation for patients with pulmonary embolism (PE).Anticoagulation is performed with unfractionated heparin (UFH) in hemodynamically unstable patients and with low molecular weight heparins (LWMH) or fondaparinux in normotensive patients. In patients with high or intermediate clinical probability of pulmonary embolism, anticoagulation should be initiated without delay while awaiting the results of diagnostic tests. LMWH and fondaparinux are preferred over UFH in the initial anticoagulation of PE since they are associated with a lower risk of bleeding.All patients with PE require therapeutic anticoagulation for at least three months. The current 2019 guidelines of the European Society of Cardiology (ESC) recommend that all eligible patients should be treated with a non-vitamin K antagonist oral anticoagulant (NOAC) in preference to a vitamin K antagonist (VKA). In patients with active cancer, Apixaban, Edoxaban and Rivaroxaban are effective alternatives to treatment with LMWH.The decision on the duration of anticoagulation should consider both, the individual risk of PE recurrence and the individual risk of bleeding. The risk for recurrent PE after discontinuation of treatment is related to the features of the index PE event. While patients with a strong transient risk factor have a low risk of recurrence and anticoagulation can be discontinued after three months, patients with strong persistent risk factor (such as active cancer) have a high risk of recurrence and thus should receive anticoagulant treatment of indefinite duration. Given the favourable safety profile of NOACs (especially if a reduced dosage of Apixaban or Rivaroxaban is initiated after at least six months of therapeutic anticoagulation), extended oral anticoagulation of indefinite duration should be considered for all patients with intermediate risk of recurrence.
Topics: Acute Disease; Dalteparin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fibrinolytic Agents; Fondaparinux; Guideline Adherence; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Neoplasms; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles
PubMed: 32668468
DOI: 10.1055/a-0955-3379 -
Carbohydrate Polymers Sep 2022Catheter-related bloodstream infections (CRBSI) are the major concern of patients undergoing hemodialysis. The current study formulates bifunctional low molecular weight...
Catheter-related bloodstream infections (CRBSI) are the major concern of patients undergoing hemodialysis. The current study formulates bifunctional low molecular weight heparin (LMWH) coated nanosilver as an effective anticoagulant and antimicrobial/anti-biofilm agent. Nanosilver formulations were prepared using a microwave-assisted green synthesis approach and stabilized with pharmaceutically approved LMWH such as dalteparin (DL) and enoxaparin (EX) along with unfractionated heparin (HP) as a control. The obtained heparinized (HP/DL/EX) nanosilver was monodisperse, and the size ranged between 15 and 25 nm. DL/EX predominantly stabilized the nanosilver by primarily engaging their negatively charged sulfate groups. The obtained DL/EX coated nanosilver are hemocompatible, showed two times increase in their anticoagulation activity, and are highly potent in inhibiting/eradicating both mono- and polymicrobial biofilms. Henceforth, the observed biocompatible and enhanced bifunctional characteristics of DL/EX coated nanosilver can be used to replace the systemic antibiotics and can be an alternative catheter lock solution to prevent CRBSI in hemodialysis therapy.
Topics: Anticoagulants; Dalteparin; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Humans; Renal Dialysis; Sepsis
PubMed: 35698376
DOI: 10.1016/j.carbpol.2022.119546 -
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 -
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 -
Population Pharmacokinetic Analysis of Dalteparin in Pediatric Patients With Venous Thromboembolism.Journal of Clinical Pharmacology Feb 2021This article describes the population pharmacokinetics (PK) of dalteparin in pediatric patients with venous thromboembolism (VTE). A prospective multicenter open-label...
This article describes the population pharmacokinetics (PK) of dalteparin in pediatric patients with venous thromboembolism (VTE). A prospective multicenter open-label study was conducted in children who required anticoagulation for the treatment of VTE. The study population included children with and without cancer. The goal was to describe the pharmacokinetics of dalteparin using anti-Xa as a surrogate marker and to determine the dose required to achieve therapeutic anti-Xa levels (0.5-1.0 IU/mL). The anti-Xa data were supplemented with 2 published studies and analyzed using population pharmacokinetic approaches. The pharmacokinetics of dalteparin following subcutaneous injection in pediatric patients was described by a 1-compartment model with linear absorption and elimination. Body weight was added as a covariate on both CL/F and Vd/F as a power function with fixed exponents of 0.75 and 1.0, respectively. The estimates of CL/F and Vd/F in the full model were 929 mL/h and 7180 mL, respectively, for a reference female patient aged 12 years with body weight of 43 kg. Body weight-normalized CL/F decreased with age. Cancer status and sex did not have significant effects on CL/F and Vd/F. Simulations were conducted to select starting doses of dalteparin that would rapidly achieve therapeutic anti-Xa levels. These simulations suggested that the recommended starting doses of dalteparin administered subcutaneously in pediatric patients of different age cohort groups for treatment of VTE were 150 IU/kg every 12 hours (1 month to <2 years), 125 IU/kg every 12 hours (≥2 to <8 years), and 100 IU/kg every 12 hours (≥8 to <19 years).
Topics: Adolescent; Age Factors; Anticoagulants; Biomarkers; Body Weight; Child; Child, Preschool; Dalteparin; Factor Xa Inhibitors; Female; Humans; Infant; Infant, Newborn; Injections, Subcutaneous; Male; Metabolic Clearance Rate; Prospective Studies; Sex Factors; Venous Thromboembolism
PubMed: 32827160
DOI: 10.1002/jcph.1716 -
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