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Clinical and Applied... 2022Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct... (Review)
Review
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.
Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Humans; Incidence; Latin America; Neoplasms; Venous Thromboembolism
PubMed: 35261295
DOI: 10.1177/10760296221082988 -
Hemodialysis International.... Apr 2020Low-molecular weight heparin, such as dalteparin, is an alternative anticoagulation method in conventional hemodialysis (HD). However, there are limited studies on its...
INTRODUCTION
Low-molecular weight heparin, such as dalteparin, is an alternative anticoagulation method in conventional hemodialysis (HD). However, there are limited studies on its use in quotidian and nocturnal HD. We assessed the optimal dose, treatment efficacy, and patient safety of dalteparin in quotidian and nocturnal HD populations.
METHODS
This study included 10 quotidian (7 in-center and 3 home) and 8 nocturnal home HD patients. Dalteparin was initiated and titrated based on clotting score in these patients. Trough anti-Xa levels were measured. The dalteparin dose, the dialyzer and HD circuit clotting scores, and bleeding episodes were recorded at 4 weeks. Patients who continued dalteparin were followed to 12 months.
FINDINGS
For the 10 quotidian HD patients, the median dalteparin dose was 1875 units [1250, 2500] after 4 weeks. For nocturnal HD patients, five of the eight patients switched back to heparin due to high clotting scores while on dalteparin within 4 weeks. However, three patients continued on dalteparin at 4 weeks. After 12 months, one maintained on 5000 units and the other two maintained on 7500 units of dalteparin. All the clotting scores at month 12 were ≤2. One patient died due to an unrelated cause. For all patients who continued on dalteparin, only 9% of the HD treatments had circuit clotting score >2 after reaching stable dose. All trough anti-Xa levels were <0.1 IU/mL. There were no episodes of bleeding. Fistula compression times were not increased.
DISCUSSION
This small pilot study suggests that dalteparin can be used effectively and relatively safety in quotidian HD. However, its use in nocturnal HD was only successful in a small proportion of patients. Alternative methods, including second dalteparin bolus after 4 hours of HD treatment, should be assessed for efficacy and practicality.
Topics: Anticoagulants; Dalteparin; Female; Hemodialysis, Home; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pilot Projects; Prospective Studies; Renal Dialysis
PubMed: 31804773
DOI: 10.1111/hdi.12805 -
Angiology Sep 2023Women with a history of venous thromboembolisms (VTEs) and/or thrombophilia are at increased risk of VTE during pregnancy. We analysed our cohort of such women who were...
Women with a history of venous thromboembolisms (VTEs) and/or thrombophilia are at increased risk of VTE during pregnancy. We analysed our cohort of such women who were treated with a prophylactic doses of dalteparin. 152 pregnant women with 179 pregnancies were classified into 3 groups: (1) previous VTE without thrombophilia (122 pregnancies); (2) previous VTE with thrombophilia (26 pregnancies) and (3) thrombophilia only (31 pregnancies). They were treated with prophylactic dalteparin in the prepartum and postpartum periods or only in the postpartum period. Occurrences of symptomatic VTE and bleeding episodes were followed, as well as dalteparin discontinuation and anti-Xa activity. Symptomatic deep vein thrombosis occurred in 4 women (2.2%) with 2 episodes in group 1 (in the postpartum period) and 2 episodes in group 2 (one in the prepartum and another in the postpartum period). Seven episodes (3.9%) of minor bleeding occurred. Dalteparin was not stopped in any women. Anti-Xa levels were within the prophylactic range. Our real-world data show a low incidence of thrombosis and minor bleeding in pregnant women treated with prophylactic dalteparin. The incidence of recurrent VTE was lower than that reported in women with similar risk, but without prophylactic anticoagulation.
Topics: Female; Humans; Pregnancy; Dalteparin; Venous Thromboembolism; Pregnant Women; Risk Factors; Venous Thrombosis; Heparin, Low-Molecular-Weight; Thrombophilia; Hemorrhage; Anticoagulants
PubMed: 36113126
DOI: 10.1177/00033197221126244 -
Journal of the College of Physicians... Mar 2021To determine the effect and safety of sequential treatment with the low-molecular-weight heparin dalteparin and the direct oral anticoagulants rivaroxaban in patients... (Observational Study)
Observational Study
OBJECTIVE
To determine the effect and safety of sequential treatment with the low-molecular-weight heparin dalteparin and the direct oral anticoagulants rivaroxaban in patients with cancer- associated venous thromboembolism (VTE).
STUDY DESIGN
Observational study.
PLACE AND DURATION OF STUDY
Department of Oncology, the Second Affiliated Hospital of Soochow University, between January 2017 and September 2019.
METHODOLOGY
Patients with active cancer, diagnosed with VTE and who received sequential treatment with dalteparin and rivaroxaban, were retrospectively reviewed. Logistic regression analysis was used to identify risk factors associated with VTE recurrence.
RESULTS
Ninety-nine patients with active cancer were enrolled in the study. The median delteparin treatment time was nine days (5-20 days), and 2.8 months (1-6 months) for rivaroxaban. Sixty (60.6%) patients had eliminated VTE, and 39 (39.4%) had persistent VTE, but with relieved symptoms. No major bleeding was observed. Eleven (11.1%) patients had minor bleeding, including melena (5.1%), hematuria (3.0%), vaginal bleeding (1.0%), gingival bleeding (1.0%), and subcutaneous hemorrhage (1.0%). During the 6 months follow-up period, one (1.0%) developed pulmonary embolism, and seven (7.1%) experienced recurrent VTE. Univariate logistic regression analysis showed that bleeding occurrence and anticoagulant treatment duration were the two significant factors affecting VTE recurrence (p<0.05).
CONCLUSION
Maintenance of rivaroxaban after initial dalteparin treatment could effectively reduce the risk of VTE recurrence and was well tolerated by patients with cancer-associated VTE. However, in the clinical practice, the treatment duration is often insufficient, so it is essential to follow-up these patients to ensure sufficient treatment time. Key Words: Venous thromboembolism, Low-molecular-weight heparins, Directly oral anticoagulants, Cancer.
Topics: Anticoagulants; Dalteparin; Female; Humans; Neoplasms; Retrospective Studies; Rivaroxaban; Venous Thromboembolism
PubMed: 33775018
DOI: 10.29271/jcpsp.2021.03.294 -
Research and Practice in Thrombosis and... May 2022Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death.
BACKGROUND
Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death.
OBJECTIVES
The objective of the RIETECAT study was to compare the long-term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer.
METHODS
We used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point.
RESULTS
From January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48-1.38), major bleeding (aHR, 1.40; 95% CI, 0.80-2.46), or death (aHR, 1.07; 95% CI, 0.88-1.30) between subgroups.
CONCLUSIONS
In RIETECAT, in patients with cancer and VTE receiving full-dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6-month period.
PubMed: 35664535
DOI: 10.1002/rth2.12736 -
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 -
Cancers Jan 2022We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in...
A Phase II Study to Compare the Safety and Efficacy of Direct Oral Anticoagulants versus Subcutaneous Dalteparin for Cancer-Associated Venous Thromboembolism in Patients with Advanced Upper Gastrointestinal, Hepatobiliary and Pancreatic Cancer: PRIORITY.
BACKGROUND
We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in patients with advanced upper gastrointestinal (GI) tract, hepatobiliary, or pancreatic cancer.
METHODS
This was a multicenter, randomized, open-label, phase II trial in five centers. Patients randomly received rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily)/apixaban (10 mg twice daily for the first 7 days, then 5 mg twice daily) or dalteparin (200 IU/kg once daily for the first month, then 150 IU/kg once daily). Randomization was stratified by the Eastern Cooperative Oncology Group Performance Status, primary cancer type, active chemotherapy, and participating centers. The primary endpoint was the rates of clinically relevant bleeding (CRB) in the full analysis set (FAS).
RESULTS
A total of 90 patients were randomly assigned to the DOAC ( = 44) and dalteparin groups ( = 46) in FAS. CRB and major bleeding (MB) rates were 34.1% and 13.0% ( = 0.018) and 18.2% and 4.3% ( = 0.047) for the DOAC and dalteparin groups, respectively. Time to CRB and MB was higher in the DOAC group than in the dalteparin group (hazard ratio [HR] 2.83; = 0.031 and HR 4.32; = 0.064). Cancer involvement at the GI mucosa was also a significant risk factor for CRB. Recurrent CA-VTE occurred in 2.3% and 2.2% of patients given DOAC and dalteparin, respectively ( = 1.000).
CONCLUSION
DOAC therapy further increased the risk of bleeding compared with dalteparin in patients with active advanced upper GI tract, hepatobiliary, or pancreatic cancer, suggesting that extra caution should be taken when selecting anticoagulants for CA-VTE.
PubMed: 35158827
DOI: 10.3390/cancers14030559 -
Medicina (Kaunas, Lithuania) Feb 2023Even though low-molecular-weight heparin (LMWH), including dalteparin, has a critical role in portal vein thrombosis (PVT) treatment in liver cirrhosis (LC) patients,...
Even though low-molecular-weight heparin (LMWH), including dalteparin, has a critical role in portal vein thrombosis (PVT) treatment in liver cirrhosis (LC) patients, the predictive factors and the proper dose of dalteparin for PVT treatment and relapse have not yet been investigated. This retrospective study evaluated the records of LC patients receiving dalteparin from July 2013 to June 2019. The odds ratio (OR) and adjusted OR were calculated from univariate and multivariable analyses, respectively. Among data from 121 patients, the overall recanalization rate of all patients was 66.1% (80 patients). No history of variceal bleeding (OR 4.6, 95% CI: 1.88-11.43) and the case of newly developed thrombus before dalteparin treatment (OR 3.2, 95% CI: 1.24-8.08) were predictive factors associated with increased treatment response. Relapse of PVT occurred in 32 out of 80 patients (40%) who showed a recanalization. The risk of relapse was 3.1-3.9 times higher in those who took more than three months or more than six months from the diagnosis of PVT to dalteparin treatment compared to those who took less than these durations, respectively. In the dosing regimen, patients with the kg-based dosing regimen showed 2.6 times better response than those with the fixed dosing regimen. However, no difference in bleeding complications was observed. In the dosing regimen, the kg-based regimen that was the same as the venous thromboembolism regimen was a better option for the efficacy and safety of dalteparin therapy. Additionally, when treating PVT in LC patients, careful monitoring is recommended for patients with predictive factors for treatment response and relapse of PVT.
Topics: Humans; Heparin, Low-Molecular-Weight; Anticoagulants; Portal Vein; Dalteparin; Retrospective Studies; Liver Cirrhosis; Venous Thrombosis; Thrombosis; Recurrence
PubMed: 36837493
DOI: 10.3390/medicina59020292 -
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 -
Canadian Journal of Anaesthesia =... Jun 2023Venous thromboembolism (VTE) is a common complication of critical illness. Sex- or gender-based analyses are rarely conducted and their effect on outcomes is unknown. We... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Venous thromboembolism (VTE) is a common complication of critical illness. Sex- or gender-based analyses are rarely conducted and their effect on outcomes is unknown. We assessed for an effect modification of thromboprophylaxis (dalteparin or unfractionated heparin [UFH]) by sex on thrombotic (deep venous thrombosis [DVT], pulmonary embolism [PE], VTE) and mortality outcomes in a secondary analysis of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT).
METHODS
We conducted unadjusted analyses using Cox proportional hazards analysis, stratified by centre and admission diagnostic category, including sex, treatment, and an interaction term. Additionally, we performed adjusted analyses and assessed the credibility of our findings.
RESULTS
Critically ill female (n = 1,614) and male (n = 2,113) participants experienced similar rates of DVT, proximal DVT, PE, any VTE, ICU death, and hospital death. In unadjusted analyses, we did not find significant differences in treatment effect favouring males (vs females) treated with dalteparin (vs UFH) for proximal leg DVT, any DVT, or any PE, but found a statistically significant effect (moderate certainty) favouring dalteparin in males for any VTE (males: hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96 vs females: HR, 1.16; 95% CI, 0.81 to 1.68; P = 0.04). This effect remained after adjustment for baseline characteristics (males: HR, 0.70; 95% CI, 0.52 to 0.96 vs females: HR, 1.17; 95% CI, 0.81 to 1.68; P = 0.04) and weight (males: HR, 0.70; 95% CI, 0.52 to 0.96 vs females: HR, 1.20; 95% CI, 0.83 to 1.73; P = 0.03). We did not identify a significant effect modification by sex on mortality.
CONCLUSIONS
We found an effect modification by sex of thromboprophylaxis on VTE in critically ill patients that requires confirmation. Our findings highlight the need for sex- and gender-based analyses in acute care research.
Topics: Humans; Female; Male; Anticoagulants; Heparin; Dalteparin; Venous Thromboembolism; Critical Illness; Sex Characteristics; Pulmonary Embolism
PubMed: 37310606
DOI: 10.1007/s12630-023-02457-8