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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 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 -
Biochimica Et Biophysica Acta.... Nov 2021Fascial adipocytes are recently identified as a unique population of adipose cells, which have different developmental origins, anatomical locations, cytological and...
Fascial adipocytes are recently identified as a unique population of adipose cells, which have different developmental origins, anatomical locations, cytological and functional characteristics compared with subcutaneous or visceral adipocytes. Superficial fascia in rats (also in pigs but not obviously in mice) contains numbers of lineage committed preadipocytes which possess adipogenic potential in vivo. The present study aimed to investigate the physiological factors that contribute to fascial adipogenesis in rats. We detected that mast cells, adipose progenitor cells, and mature adipocytes distributed in certain fascia areas were closely associated with each other, and numerous heparin-loaded granules released from mast cells were distributed around fascial preadipocytes. The culture supernatants of rat peritoneal mast cells and RBL-2H3 mast cells contained 20-30 μg/ml of heparin, effectively activated PPAR-responsive luciferase activity, promoted mRNA and protein expressions of key adipogenic genes, and hence increased adipogenic differentiation of fascia- or epididymal adipose-derived stromal cells. Adipogenic effects of mast cell supernatants were mimicked by heparin but not by histamine or 5-hydroxytryptamine, and were antagonized by protamine sulfate. In rats, local administration of heparin-loaded microspheres for 30 days induced adipogenesis in local areas of superficial fascia. This adipogenic effects of heparin might be related by chain length of glucosamine units, because heparin stimulated stronger adipogenesis than dalteparin and enoxaparin with relatively short chains. Our findings suggested that mast cell and its granule heparin could serve as the endogenous physiological factors to initiate and accelerate local adipogenesis in superficial fascia, or in adipose tissue with the fascia naturally embedded inside.
Topics: Adipogenesis; Animals; Cells, Cultured; Heparin; Male; Mast Cells; Rats; Rats, Sprague-Dawley; Subcutaneous Tissue
PubMed: 34389520
DOI: 10.1016/j.bbalip.2021.159024 -
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 -
Annales de Dermatologie Et de... Mar 2022Bullous haemorrhagic dermatitis (BHD) is an uncommon and highly particular side effect of various forms of heparins. (Review)
Review
BACKGROUND
Bullous haemorrhagic dermatitis (BHD) is an uncommon and highly particular side effect of various forms of heparins.
METHODS
To better characterise the disease, we collected all cases from French Pharmacovigilance centres recorded over a 20-year period (37 cases) and performed a Medline literature search up to June 2020 (57 cases).
RESULTS
In all, 94 patients were identified (male/female ratio: 2.2) of mean age 73.5±12.1 years (31-94). Patients were treated with enoxaparin (n=66), unfractionated heparin (n=11), fondaparinux (n=10), tinzaparin (n=4), bemiparin (n=1), reviparin (n=1), dalteparin (n=1), and 4 with other anticoagulants: warfarin (n=3) and rivaroxaban (n=1). All cases presented with 1 to more than 100 haemorrhagic vesicles and bullae, distant from the injection sites, located mainly on the lower (75%) or upper limbs (69%). The lesions were asymptomatic, except in 5 patients who had pruritic or painful lesions. The interval between treatment initiation and BHD ranged from 6 hours to 30 days (mean: 8.4±7 days). Biopsy (n=53) showed intraepidermal or subcorneal cavity with red cells (n=39) or junctional blisters (n=10), with eosinophilic infiltrate only rarely. Direct immuno-fluorescence was negative in 19/20 cases and indirect immunofluorescence was negative in 8/8. The outcome was favourable in all cases, including in 12 patients for whom heparin was maintained. A 93-year-old patient died of compressive haematomas unrelated to BHD. We found 5 cases similar to BHD due to other anticoagulants.
DISCUSSION
This is the largest comprehensive series of this adverse effect due to heparins or, more rarely, to other anticoagulants. Dermatologists must be aware of BHD, since this benign side effect does not necessarily require interruption of treatment. It is rare, considering the large-scale prescription of heparins, and occurs mainly in male patients aged over 70. Although the presentation is highly typical, the physiopathology is difficult to understand, as coagulation parameters are usually normal. Aging, skin fragility or mechanical factors might play a role.
Topics: Aged; Aged, 80 and over; Anticoagulants; Dermatitis; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pharmacovigilance
PubMed: 34175142
DOI: 10.1016/j.annder.2021.05.003