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Thrombosis and Haemostasis May 2022Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.5%), lung in 200 (17.3%), breast in 155 (13.4%), genitourinary sites in 139 (12%), gynecological sites in 119 (10.3%), and was hematological in 85 patients (7.4%). Rates of VTE recurrence were 10.9% in patients with gynecological, 8.8% with gastrointestinal, 6.5% with genitourinary, and 5.5% with lung cancer with lower rates in the other sites of cancer. Rates of major bleeding were 7.2% in patients with genitourinary and 4.8% with gastrointestinal cancer, with lower rates in patients with other sites of cancer. The observed absolute risk difference in VTE recurrence in favor of apixaban was 11.9% in patients with gynecological, 5.5% with lung, 3.7% with genitourinary cancer, and 0.6% with gastrointestinal cancer. None of the risk differences was statistically significant. The rates of major bleeding in patients treated with apixaban or dalteparin was similar across patients with different cancer sites. In conclusion, recurrences appear to be more common in patients with gastrointestinal and gynecological cancer and major bleedings in patients with genitourinary and gastrointestinal cancer. Oral apixaban is a valid oral alternative to subcutaneous dalteparin for the treatment of a large spectrum of patients with cancer-associated VTE.
Topics: Anticoagulants; Dalteparin; Hemorrhage; Humans; Neoplasms; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 34530482
DOI: 10.1055/s-0041-1735194 -
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 -
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 -
Respiration; International Review of... 2019Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has... (Comparative Study)
Comparative Study
BACKGROUND
Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear.
OBJECTIVES
We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer.
METHODS
A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality.
RESULTS
The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337).
CONCLUSIONS
There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.
Topics: Aged; Anticoagulants; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Cause of Death; Dalteparin; Duration of Therapy; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Lung Neoplasms; Male; Middle Aged; Mortality; Proportional Hazards Models; Pulmonary Embolism; Recurrence; Respiratory Tract Diseases; Retrospective Studies; Rivaroxaban; Small Cell Lung Carcinoma; Venous Thromboembolism; Venous Thrombosis
PubMed: 31096241
DOI: 10.1159/000499895 -
The Canadian Journal of Hospital... 2015The choice of whether to monitor anti-factor Xa (anti-Xa) activity in patients who are obese and who are receiving low-molecular-weight heparin (LMWH) therapy is... (Review)
Review
BACKGROUND
The choice of whether to monitor anti-factor Xa (anti-Xa) activity in patients who are obese and who are receiving low-molecular-weight heparin (LMWH) therapy is controversial. To the authors' knowledge, no systematic review of monitoring of anti-Xa activity in such patients has been published to date.
OBJECTIVE
To systematically ascertain the utility of monitoring anti-Xa concentrations for LMWH therapy in obese patients.
DATA SOURCES
MEDLINE (1946 to September 2014), the Cochrane Database of Systematic Reviews, Embase (1974 to September 2014), PubMed (1947 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), and Scopus were searched using the terms obesity, morbid obesity, thrombosis, venous thrombosis, embolism, venous thromboembolism, pulmonary embolism, low-molecular weight heparin, enoxaparin, dalteparin, tinzaparin, anti-factor Xa, anti-factor Xa monitoring, anti-factor Xa activity, and anti-factor Xa assay. The reference lists of retrieved articles were also reviewed.
STUDY SELECTION AND DATA EXTRACTION
English-language studies describing obese patients treated with LMWH or reporting anti-Xa activity were reviewed using a 9-step decision-making algorithm to determine whether monitoring of LMWH therapy by means of anti-Xa activity in obesity is warranted. Studies published in abstract form were excluded.
DATA SYNTHESIS
The analysis showed that anti-Xa concentrations are not strongly associated with thrombosis or hemorrhage. In clinical studies of LMWH for thromboprophylaxis in bariatric surgery, orthopedic surgery, general surgery, and medical patients, and for treatment of venous thrombo embolism and acute coronary syndrome, anti-Xa activity can be predicted from dose of LMWH and total body weight; no difference in clinical outcome was found between obese and non-obese participants.
CONCLUSIONS
Routinely determining anti-Xa concentrations in obese patients to monitor the clinical effectiveness of LMWH is not warranted on the basis of the current evidence. Circumstances where measurement of anti-Xa concentration may help in clinical decision-making in either obese or non-obese patients would be cases where elimination of LMWH is impaired or there is an unexpected clinical response, as well as to confirm compliance with therapy or to identify deviation from predicted pharmacokinetics.
PubMed: 25762818
DOI: 10.4212/cjhp.v68i1.1423 -
Acta Neurochirurgica May 2016A postoperative haematoma can be a very serious complication following a neurosurgical procedure. Patients should be informed about the risks of such an event prior to...
BACKGROUND
A postoperative haematoma can be a very serious complication following a neurosurgical procedure. Patients should be informed about the risks of such an event prior to surgery. From a practical point of view, it would be important to know when the patient is most likely to deteriorate and to require surgery because of a postoperative haematoma and when it might be safe to transfer the patient to the regular ward. The up-to-date studies regarding this topic are few.
METHODS
We therefore undertook the present retrospective study, including a cohort of all patients operated on at the Department of Neurosurgery in Lund during the years 2011-2014, with the aim to define the time windows for clinical deterioration and reoperation, and whether risk factors such as anticoagulant agents/antiplatelet therapy, emergency versus elective surgery and abnormal coagulation blood values were present. We also defined the type of surgery resulting in postoperative haematoma and tried to find the clinical state of the patients when they deteriorated, as well as the outcome at 3 months postoperatively.
RESULTS
During the time period from June 2011 to November 2014, a total of 7,055 surgical procedures of all kinds were registered at our department. By the search for the diagnosis codes AWE00 and AWD00 (reoperation for deep haemorrhage and for superficial haemorrhage respectively), we identified 93 reoperations, meaning a percentage of 1.3 %. Thirty-four of the reoperations were done within the first 24 h. Twenty-four patients were reoperated on >24 h but ≤72 h after the first operation. Only four patients who were initially doing well postoperatively showed a delayed clinical deterioration within the time frame from >6 h and ≤24 h postoperatively. This means that 0.06 % of the patients who were operated upon were doing well initially, being completely awake and with no new neurological deficit and no deterioration within the first 6 h postoperatively, and then deteriorated from a postoperative haematoma within the time frame of >6 h and ≤24 h postoperatively.
CONCLUSIONS
We could conclude that no exact time window distinguished very early from somewhat later postoperative haematomas in our material. However, all but two patients deteriorating between 6 and 24 h after the operation had at least one of the following risk factors defined for post-operative haematoma: meningioma surgery, anticoagulant agents/antiplatelet therapy prior to surgery (including Dalteparin [Fragmin®], Enoxaparinnatrium [Klexane®], Warfarin [Waran®], ASA [Trombyl®] or ASA and caffeine [Treo®]), emergency operation, posterior fossa surgery or chronic subdural haematoma in a patient with a shunt. This material is too small to make any definitive conclusions, but a suggestion could be to include these factors when considering the transfer of a patient from the postoperative intensive care unit to the regular ward.
Topics: Adult; Aged; Anticoagulants; Female; Hematoma; Humans; Intensive Care Units; Male; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Postoperative Period; Reoperation; Retrospective Studies; Risk Factors
PubMed: 27020442
DOI: 10.1007/s00701-016-2778-4 -
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 -
PharmacoEconomics May 2017Total hip replacement (THR) and total knee replacement (TKR) surgeries are being performed with increasing regularity and are associated with a high risk of developing a... (Comparative Study)
Comparative Study Review
BACKGROUND
Total hip replacement (THR) and total knee replacement (TKR) surgeries are being performed with increasing regularity and are associated with a high risk of developing a venous thromboembolism (VTE). New oral anticoagulants (NOACs) may be more effective at preventing VTEs but are associated with more bleeding events versus traditional anticoagulants.
OBJECTIVE
The objective of this systematic review was to identify published economic analyses of NOACs for primary VTE prophylaxis following THR and TKR surgeries, and to summarise the modelling techniques used and the cost-effectiveness results.
METHODS
Electronic searches of MEDLINE, EconLit and The Cochrane Library were performed from January 2008 to February 2015. Reference lists of included articles and reviews were examined for relevant studies.
RESULTS
Sixteen relevant economic analyses were identified, all of which used decision-tree structures to model acute events after surgery; 13 included a chronic-phase Markov module to capture long-term complications of VTE and recurrent VTE events. All studies included prophylaxis-related major bleeding events and captured both symptomatic and asymptomatic VTE-related events; nine studies distinguished between distal and proximal deep vein thrombosis events. Overall, rivaroxaban dominated enoxaparin in eight of 11 studies and dalteparin in one study, dabigatran dominated enoxaparin in five of seven studies and apixaban dominated enoxaparin in two of two studies. Rivaroxaban dominated dabigatran in four of four studies, apixaban dominated dabigatran in two of two studies and rivaroxaban dominated apixaban in one study.
CONCLUSIONS
The economic analyses showed reasonable consistency in the model structures used and the events captured. The results strongly suggested that NOACs are cost effective alternatives to low molecular-weight heparin. Dabigatran appeared to be the least cost effective NOAC. More research is needed to assess the cost effectiveness of apixaban and edoxaban.
Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Decision Trees; Humans; Markov Chains; Models, Economic; Venous Thromboembolism
PubMed: 28185212
DOI: 10.1007/s40273-017-0486-4 -
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 -
European Journal of Clinical... Aug 2015Although therapeutic dosages of most low-molecular-weight heparins (LMWHs) are known to accumulate in patients with renal insufficiency, for the lower prophylactic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Although therapeutic dosages of most low-molecular-weight heparins (LMWHs) are known to accumulate in patients with renal insufficiency, for the lower prophylactic dosages this has not been clearly proven. Nevertheless, dose reduction is often recommended. We conducted a systematic review to investigate whether prophylactic dosages of LMWH accumulate in renal insufficient patients.
METHODS
A comprehensive search was conducted on 17 February 2015 using Embase, Medline, Web of Science, Scopus, Cochrane, PubMed publisher, and Google scholar. The syntax emphasized for LMWHs, impaired renal function, and pharmacokinetics. The search yielded 674 publications. After exclusion by reading the titles, abstracts, and if necessary the full paper, 11 publications remained.
RESULTS
For dalteparin and tinzaparin, no accumulation was observed. Enoxaparin, on the other hand, did lead to accumulation in patients with renal insufficiency, although not in patients undergoing renal replacement therapy. Bemiparin and certoparin also did show accumulation. No data were available for nadroparin.
CONCLUSIONS
In this systematic review, we show that prophylactic dosages of tinzaparin and dalteparin are likely to be safe in patients with renal insufficiency and do not need dose reduction based on the absence of accumulation. However, prophylactic dosages of enoxaparin, bemiparin, and certoparin did show accumulation in patients with a creatinine clearance (CrCl) below 30 ml/min, and therefore, dose reduction is required. The differences in occurrence of accumulation seem to depend on the mean molecular weight of LMWHs.
Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Renal Insufficiency; Venous Thrombosis
PubMed: 26071276
DOI: 10.1007/s00228-015-1880-5