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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 -
BMC Pregnancy and Childbirth Oct 2021To compare three commonly used low-molecular-weight heparins (LWMHs) in the treatment of recurrent spontaneous abortion (RSA) by evaluating the anti-Xa peak levels and... (Comparative Study)
Comparative Study Observational Study
Effect of low-molecular-weight heparins on anti-Xa peak levels and adverse reactions in Chinese patients with recurrent spontaneous abortion: a single-center, observational study.
OBJECTIVE
To compare three commonly used low-molecular-weight heparins (LWMHs) in the treatment of recurrent spontaneous abortion (RSA) by evaluating the anti-Xa peak levels and adverse reactions.
METHODS
In this single-center, observational study, we enrolled 310 patients with RSA in whom anti-Xa levels were measured during pregnancy. Patients were divided into three groups according to the LMWH they used: the nadroparin group, enoxaparin group and dalteparin group. We compared the peak anti-Xa levels and the coagulation status of each group, and analyzed the incidence of adverse reactions, including local allergy, liver and renal dysfunction, and the impact on platelet.
RESULTS
Patients in the enoxaparin group had a higher anti-Xa peak level than those in the nadroparin group (0.80 ± 0.22 IU/ml vs. 0.61 ± 0.24 IU/ml; P < 0.0001), although most patients in the three groups reached the target concentration of anti-Xa. Furthermore, patients in the enoxaparin group had a more stable anti-Xa levels during pregnancy. In addition, patients in the nadroparin group had a higher rate of local allergy than those in the enoxaparin group (60.5% vs. 42.5%; P = 0.004) and those in the dalteparin group (60.5% vs. 33.3%; P = 0.002). Further examination by the type of local allergy indicated a dramatic difference in pruritus and induration between the nadroparin group and the other two groups. No difference was found in the incidence of liver and renal dysfunction and thrombocytopenia.
CONCLUSION
Compared with nadroparin and daltepatin, enoxaparin showed a better performance regarding anti-Xa levels and the incidence of adverse reactions in the treatment of RSA.
Topics: Abortion, Habitual; Adult; Anticoagulants; Asian People; Blood Coagulation; China; Dalteparin; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Enoxaparin; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Nadroparin; Pregnancy
PubMed: 34620101
DOI: 10.1186/s12884-021-04161-1 -
BMC Veterinary Research Sep 2021Lobular dissecting hepatitis (LDH) is a rare form of canine liver cirrhosis that may be accompanied by portal hypertension in American Cocker Spaniels. In human patients...
BACKGROUND
Lobular dissecting hepatitis (LDH) is a rare form of canine liver cirrhosis that may be accompanied by portal hypertension in American Cocker Spaniels. In human patients with liver cirrhosis, portal vein thrombosis (PVT) is a common complication. However, PVT has not been reported in dogs with LDH. Herein, we describe the long-term follow-up of PVT in an American Cocker Spaniel with LDH.
CASE PRESENTATION
An 8-year-old neutered male American Cocker Spaniel presented with a 1-month history of severe abdominal effusion. The dog was histopathologically diagnosed with LDH and treated with low-dose prednisolone on day 14. On day 115, computed tomography angiography (CTA) confirmed the presence of a thrombus in the portal vein. Therefore, the dog was subcutaneously administered with the anticoagulant dalteparin, and low-dose prednisolone was continued. As a follow-up for PVT, CTA examinations were performed on days 207, 515, 886, and 1168, and the dog's antithrombin and D-dimer levels were measured. Following anticoagulant therapy, the dog was confirmed to have gradually increased antithrombin activity and decreased D-dimer concentrations. In addition, although the thrombus was confirmed to be in the same area of the portal vein system by CTA, atrophy and increased CT values due to organization were observed during the follow-up period. The dog's condition remained stable without clinical signs until day 1112 when it developed hepatic encephalopathy. The dog died on day 1208. On postmortem examination, histopathologically, the liver showed marked bile duct hyperplasia and fibrosis with chronic thrombus in the portal vein.
CONCLUSIONS
This case demonstrated that low-dose glucocorticoid combined with dalteparin allowed long-term follow-up of PVT in an American Cocker Spaniel with LDH.
Topics: Animals; Anticoagulants; Computed Tomography Angiography; Dalteparin; Dog Diseases; Dogs; Follow-Up Studies; Hepatitis; Liver Cirrhosis; Male; Portal Vein; Prednisolone; Venous Thrombosis
PubMed: 34592989
DOI: 10.1186/s12917-021-03017-2 -
Blood Mar 2022Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel...
Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel therapies, so too has the treatment of VTE. Therapeutic options for the treatment of cancer-associated VTE have expanded from only warfarin and low-molecular-weight heparins (LMWHs) to include the direct oral anticoagulants (DOACs) apixaban, edoxaban and rivaroxaban. There have been no head-to-head trials comparing different DOACs in this setting, and randomized trials comparing a DOAC with LMWH dalteparin differ in trial design and results. Drug-drug interactions, drug-specific side effects, and patient selection are important considerations when prescribing anticoagulant therapy. In all patients, the relative risks of thrombosis and bleeding, the availability of the anticoagulant, and the life expectancy of the patient are vital elements in selecting the most appropriate anticoagulant (which can vary over time) for the individual patient. We describe the intricacies and challenges of treating thrombotic complications in patients with lymphoma with an emphasis on evidence and guideline-based care.
Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Lymphoma; Neoplasms; Thrombosis; Venous Thromboembolism
PubMed: 34479364
DOI: 10.1182/blood.2019003689 -
Journal of Thrombosis and Haemostasis :... Dec 2021In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients.
OBJECTIVES
To evaluate risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban.
PATIENTS/METHODS
In this nested case-control study in patients with gastrointestinal cancer randomized to edoxaban in the Hokusai VTE Cancer study, cases (patients with clinically relevant gastrointestinal bleeding during treatment) were randomly matched to three controls (patients who had no gastrointestinal bleeding). Data for the 4-week period prior to bleeding were retrospectively collected. Odds ratios (ORs) were calculated in a crude conditional logistic regression model and a multivariable model adjusted for age, sex, and cancer type.
RESULTS
Twenty-four cases and 64 matched controls were included. In the multivariable analysis, advanced cancer, defined as regionally advanced or metastatic cancer (OR 3.6, 95% CI 1.01-12.6) and low hemoglobin levels (OR 4.8, 95% CI 1.5-16.0) were significantly associated with bleeding. There was no significant difference in patients with resected tumors (OR 0.4, 95% CI 0.1-1.4), or in patients on chemotherapy (OR 1.3, 95% CI 0.5-3.5).
CONCLUSION
Advanced cancer and low hemoglobin levels were associated with an increased risk of gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. We were unable to identify other risk factors, mainly due to limited statistical power.
Topics: Anticoagulants; Case-Control Studies; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Pyridines; Retrospective Studies; Risk Factors; Thiazoles; Venous Thromboembolism
PubMed: 34455706
DOI: 10.1111/jth.15516 -
JACC. CardioOncology Sep 2020Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli....
BACKGROUND
Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli. Patients with cancer may also have an increased risk of bleeding with anticoagulant treatment. Recent trials have reported that direct oral anticoagulants (DOACs) are noninferior to the low-molecular-weight heparin, dalteparin, in preventing VTE, but have a higher bleeding rate.
OBJECTIVES
This study compared the efficacy and risks of DOACs versus dalteparin in patients with cancer-related VTEs across all randomized controlled trials (RCTs).
METHODS
This study performed a systematic analysis of RCTs published in PubMed, SCOPUS, and Google Scholar from September 1, 2007 through March 31, 2020 that reported clinical outcomes of treatment with DOACs versus dalteparin in patients with cancer with acute VTE. Two investigators independently performed study selection and data extraction. Extracted data were recorded and exported to statistical software for all analyses (OpenMetaAnalyst).
RESULTS
This study included 4 randomized trials (N = 2,907). Compared with DOACs, dalteparin was associated with higher VTE recurrence (risk ratio [RR]: 1.55; 95% confidence interval [CI]: 1.19 to 2.03; p = 0.001), whereas clinically relevant nonmajor bleeding (CRNMB) was significantly less frequent with dalteparin than that with DOACs (RR: 0.68; 95% CI: 0.54 to 0.86; p = 0.001). The risk of CRNMB was largely observed with patients with gastrointestinal malignancies. No significant differences were observed in major bleeding (RR: 0.74; 95% CI: 0.52 to 1.06; p = 0.11).
CONCLUSIONS
DOACs were noninferior to dalteparin in preventing VTE recurrence in patients with cancer without a significantly increased risk of major bleeding. However, DOACs were associated with higher rates of CRNMB compared with dalteparin, primarily in patients with gastrointestinal malignancies.
PubMed: 34396250
DOI: 10.1016/j.jaccao.2020.06.001 -
Haematologica Jul 2022The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism... (Randomized Controlled Trial)
Randomized Controlled Trial
Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial.
The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancerassociated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60- 89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: NCT03045406.
Topics: Anticoagulants; Dalteparin; Hemorrhage; Humans; Kidney; Neoplasms; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 34382385
DOI: 10.3324/haematol.2021.279072 -
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 -
The Journal of Arthroplasty Oct 2021Optimum venous thromboembolism (VTE) prophylaxis for patients undergoing total hip or knee arthroplasty remains undefined. The purpose of this study is to compare... (Observational Study)
Observational Study
No Increased Risk of Venous Thromboembolism in High-Risk Patients Continuing Their Dose of 75 mg Aspirin Compared to Healthier Patients Given Low-Molecular-Weight Heparin.
BACKGROUND
Optimum venous thromboembolism (VTE) prophylaxis for patients undergoing total hip or knee arthroplasty remains undefined. The purpose of this study is to compare complication rates among total joint arthroplasty patients using either low-dose aspirin (75 mg once daily) or low-molecular-weight heparin (LMWH; Fragmin/dalteparin 5000 U) for VTE prophylaxis.
METHODS
This is a prospective observational study. All total hip or knee arthroplasties from 2014 to 2020 were included. One thousand eighty-four patients already taking aspirin 75 mg as primary or secondary prophylaxis for cardiovascular disease continued their daily aspirin dose throughout their hospital stay and after discharge without any other kind of thromboprophylaxis. Five thousand ten patients not already taking aspirin were given LMWH for 12-14 days starting the day of surgery. Both groups consisted of patients undergoing either primary or revision total hip or knee arthroplasty. The aspirin group was older (73 ± 7.8 vs 66 ± 10.2 years, P < .01, 95% CI -7.6, -6.3) with more comorbidities but otherwise did not differ from the LMWH group. Outcome measures were recorded at 3-month follow-up and included the following complications: clinically deep venous thrombosis (DVT), pulmonary embolism (PE), deep infection, blood transfusion, and death.
RESULTS
The aspirin group had 0.28% DVT and 0.28% PE, and the LMWH group had 0.24% DVT and 0.16% PE (P = .42 and .74, respectively). No difference in deep infection, allogenic blood transfusion, or mortality was found.
CONCLUSION
No statistically significant difference in complication rates was found between aspirin 75 mg and LMWH used for VTE prophylaxis. Aspirin 75 mg daily is safe for VTE prophylaxis after total hip or knee arthroplasty.
Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Heparin, Low-Molecular-Weight; Humans; Postoperative Complications; Venous Thromboembolism
PubMed: 34176693
DOI: 10.1016/j.arth.2021.06.001