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Innovative Surgical Sciences Dec 2019About 10% of patients taking a chronic, oral anticoagulant therapy require an invasive procedure that can be associated with an increased risk for peri-interventional or... (Review)
Review
About 10% of patients taking a chronic, oral anticoagulant therapy require an invasive procedure that can be associated with an increased risk for peri-interventional or perioperative bleeding. Depending on the risk for thromboembolism and the risk for bleeding, the physician has to decide whether the anticoagulant therapy should be interrupted or continued. Patient characteristics such as age, renal function and drug interactions must be considered. The perioperative handling of the oral anticoagulant therapy differs according to the periprocedural bleeding risk. Patients requiring a procedure with a minor risk for bleeding do not need to pause their anticoagulant therapy. For procedures with an increased risk for perioperative bleeding, the anticoagulant therapy should be adequately paused. For patients on a coumarin derivative with a high risk for a thromboembolic event, a perioperative bridging therapy with a low molecular weight heparin is recommended. Due to an increased risk for perioperative bleeding in patients on a bridging therapy, it is not recommended in patients with a low risk for thromboembolism. For patients taking a non-vitamin K oral anticoagulant, a bridging therapy is not recommended due to the fast onset and offset of the medication.
PubMed: 33977124
DOI: 10.1515/iss-2019-0004 -
TH Open : Companion Journal To... Jul 2019Direct oral anticoagulants (DOACs) represent an attractive alternative to low-molecular-weight heparins (LMWHs) for the long-term treatment of cancer-associated... (Review)
Review
Direct oral anticoagulants (DOACs) represent an attractive alternative to low-molecular-weight heparins (LMWHs) for the long-term treatment of cancer-associated thrombosis (CT) since they avoid the burden of daily injections. Analyses in subgroups of cancer patients from large randomized trials suggested that DOACs were at least as effective as vitamin K antagonists, while indirect comparisons suggested that DOACs' efficacy and safety profile were comparable to those of LMWHs. In the randomized controlled HOKUSAI-VTE Cancer study, currently the only completed phase III trial on DOACs in CT patients, edoxaban was shown noninferior to dalteparin on the composite primary endpoint of time to first recurrent venous thromboembolism or major bleeding during the 12 months after randomization. Study results suggest that both agents had comparable benefit/risk ratio in patients with CT. Even though this conclusion was valid from a strict statistical viewpoint, it was potentially misleading when interpreting benefit/risk ratios. Besides the obvious heterogeneity of the study population (e.g., 23% of patients no longer had cancer) and significantly different treatment durations between arms, secondary outcomes for efficacy were in favor of edoxaban for recurrent deep-vein thrombosis but not for recurrent pulmonary embolism, and major bleeding episodes were significantly more frequent in the edoxaban group, with an excess of gastrointestinal (GI) bleeding episodes observed mainly but not only in patients with GI cancers. More research is needed regarding specific patients' profiles, cancer types, and treatment period to better clarify the respective roles of DOACs and LMWHs in CT patients.
PubMed: 31535076
DOI: 10.1055/s-0039-1696659 -
Clinical Cardiology Jan 2000The low-molecular-weight heparins (LMWHs) have a number of therapeutic advantages, relative to standard unfractionated heparin (UFH). They are readily bioavailable when... (Review)
Review
The low-molecular-weight heparins (LMWHs) have a number of therapeutic advantages, relative to standard unfractionated heparin (UFH). They are readily bioavailable when injected subcutaneously and can be given in fixed doses, allowing for far simpler administration. Several LMWHs are now commercially available, each demonstrating different physical and chemical properties and different activities in animal models of anticoagulation or hemorrhage. In clinical comparisons with placebo in the treatment of unstable coronary artery disease (UCAD), the LMWHs dalteparin sodium and nadroparin calcium have demonstrated good anticoagulant efficacy. In comparisons with UFH, on the other hand, only enoxaparin has shown superior anticoagulant activity, as reported in the results of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis In Myocardial Infarction (TIMI) 11B trials. However, close scrutiny of the methodology of the clinical trials in UCAD reveals considerable differences in study designs, dosage regimens, duration of administration of active treatments, and the timing and definition of endpoints. Therefore, it would not be scientifically sound to compare results with the different LMWHs based on the current available studies. It is also not possible to draw any conclusions with regard to the relative efficacy of the different LMWHs, since there are no properly-sized comparative data between dalteparin sodium, enoxaparin sodium, and nadroparin calcium.
Topics: Anticoagulants; Clinical Trials as Topic; Coronary Thrombosis; Dalteparin; Drug Administration Schedule; Enoxaparin; Heparin, Low-Molecular-Weight; Humans; Nadroparin; Research Design
PubMed: 10680037
DOI: 10.1002/clc.4960231303 -
Proceedings of the National Academy of... Oct 2022The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell...
The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell motility. This mechanical work is driven by the ATPase activity at the catalytic site in the F-form. For deeper understanding of the actin cellular functions, the reaction mechanism must be elucidated. Here, we show that a single actin molecule is trapped in the F-form by fragmin domain-1 binding and present their crystal structures in the ATP analog-, ADP-Pi-, and ADP-bound forms, at 1.15-Å resolutions. The G-to-F conformational transition shifts the side chains of Gln137 and His161, which relocate four water molecules including W1 (attacking water) and W2 (helping water) to facilitate the hydrolysis. By applying quantum mechanics/molecular mechanics calculations to the structures, we have revealed a consistent and comprehensive reaction path of ATP hydrolysis by the F-form actin. The reaction path consists of four steps: 1) W1 and W2 rotations; 2) P-O bond cleavage; 3) four concomitant events: W1-PO formation, OH and proton cleavage, nucleophilic attack by the OH against P, and the abstracted proton transfer; and 4) proton relocation that stabilizes the ADP-Pi-bound F-form actin. The mechanism explains the slow rate of ATP hydrolysis by actin and the irreversibility of the hydrolysis reaction. While the catalytic strategy of actin ATP hydrolysis is essentially the same as those of motor proteins like myosin, the process after the hydrolysis is distinct and discussed in terms of Pi release, F-form destabilization, and global conformational changes.
Topics: Actins; Adenosine Diphosphate; Adenosine Triphosphate; Dalteparin; Hydrolysis; Myosins; Protons; Water
PubMed: 36252034
DOI: 10.1073/pnas.2122641119 -
Journal of Cancer Research and... Dec 2018To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α...
PURPOSE
To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α (HIF-1α) in A549 human lung cancer (LC) cell line and a human A549-grafted nude mouse model.
MATERIALS AND METHODS
A549 human lung adenocarcinoma cell line was divided into control group, treated using normal saline (NS); and dalteparin sodium groups, receiving 5, 15, 50, and 150 IU/ml of dalteparin sodium, respectively. Human A549-grafted nude mouse was induced through subcutaneous (SC) injection of A549 (5 × 10/0.2 ml) into the right armpit, and randomly assigned into control group (n = 6) receiving intraperitoneal (i.p.) injection of NS, cisplatin (DDP) group (n = 6, 3 mg/kg DDP alone, i.p., for 3 days), low molecular weight heparin (LMWH) group (n = 6) receiving SC injection of 1500 IU/kg dalteparin sodium for 35 days, and DDP plus LMWH group (n = 6, 3 mg/kg DDP, i.p., for 3 days, followed by SC injection of 1500 IU/kg dalteparin sodium for 35 days).
RESULTS
Significant difference was noted in the messenger RNA expression of VEGF, VEGFR, and HIF-1α after treating with heparin with a concentration of 15, 50, or 150 IU/ml in the A549 cell line at 24 and 48 h, respectively. In the human A549-grafted nude mouse model, a significant reduction was noted in the expression of VEGF, VEGFR, and HIF-1α in the tumor mass harvested from the mice receiving administration of dalteparin sodium plus DDP.
CONCLUSION
Dalteparin sodium had the inhibitory effects on the growth of human LC A549 cells in vitro and A549 LC xenograft model, which could be enhanced when administrated together with DDP.
Topics: A549 Cells; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Cisplatin; Dalteparin; Drug Synergism; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Receptors, Vascular Endothelial Growth Factor; Treatment Outcome; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays
PubMed: 30539834
DOI: 10.4103/0973-1482.192765 -
Canadian Family Physician Medecin de... Feb 2005A few years ago I suffered from pulmonary emboli. My physician recommended I use dalteparin during this pregnancy although, during my previous pregnancy, I had received... (Review)
Review
QUESTION
A few years ago I suffered from pulmonary emboli. My physician recommended I use dalteparin during this pregnancy although, during my previous pregnancy, I had received subcutaneous heparin injections three times daily. Is dalteparin the same as heparin?
ANSWER
: Based on the best available evidence from mostly small prospective case series, retrospective reports, and placental perfusion studies, low-molecular-weight heparins (LMWHs), such as dalteparin, are a safe and convenient alternative to heparin during pregnancy for both mothers and fetuses.
Topics: Anticoagulants; Dalteparin; Female; Heparin, Low-Molecular-Weight; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism
PubMed: 15751560
DOI: No ID Found -
British Journal of Anaesthesia Aug 2006
Topics: Anesthesia; Anesthesia, Epidural; Anesthesia, Spinal; Anticoagulants; Clopidogrel; Dalteparin; Hematoma, Epidural, Spinal; Humans; Platelet Aggregation Inhibitors; Ticlopidine
PubMed: 16831879
DOI: 10.1093/bja/ael164 -
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 -
Annals of Oncology : Official Journal... Jun 2019Anticoagulation for cancer-associated venous thromboembolism (VTE) can be challenging due to complications-including bleeding and potential drug-drug interactions with... (Review)
Review
Anticoagulation for cancer-associated venous thromboembolism (VTE) can be challenging due to complications-including bleeding and potential drug-drug interactions with chemotherapy-associated with vitamin K antagonists and inconvenience of low-molecular-weight heparin (LMWH). Direct oral anticoagulants (DOACs) could partially overcome these issues, but until recently there were no large clinical trials assessing their efficacy and safety in cancer patients. This review summarizes clinical treatment guidelines, prior clinical and real-world evidence for anticoagulant choice, recent clinical trials assessing DOACs for cancer-associated VTE (i.e. Hokusai-VTE Cancer, SELECT-D, CARAVAGGIO, and ADAM VTE), and special considerations for DOAC use. Based on established data, clinical guidelines recommend patients with cancer-associated VTE receive LMWH treatment of at least 3-6 months. Nevertheless, LMWH is underused and associated with poor compliance and persistence in these patients relative to oral anticoagulants. Clinical data supporting DOAC use in cancer patients are becoming available. In Hokusai-VTE Cancer, edoxaban was noninferior to dalteparin for the composite of recurrent VTE and major bleeding (12.8% versus 13.5%), with numerically lower recurrent VTE (7.9% versus 11.3%) and significantly higher major bleeding (6.9% versus 4.0%); only patients with gastrointestinal cancer had significantly higher risk of bleeding with edoxaban. In SELECT-D, rivaroxaban had numerically lower VTE recurrence (4% versus 11%), comparable major bleeding (6% versus 4%), and numerically higher clinically relevant nonmajor bleeding (13% versus 4%) versus dalteparin. Most bleeding events were gastrointestinal or urologic; patients with esophageal/gastroesophageal cancer had higher rates of major bleeding with rivaroxaban (36% versus 11%). For comparison of apixaban versus dalteparin, CARAVAGGIO is ongoing, and preliminary results from ADAM VTE are favorable. This review concludes that DOACs appear to be reasonable alternatives to LMWH for treatment of cancer-associated VTE. In patients with gastrointestinal cancer, DOAC use should be considered on a case-by-case basis with consideration of the relative risks and benefits.
Topics: Administration, Oral; Anticoagulants; Clinical Trials as Topic; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Venous Thromboembolism
PubMed: 30918939
DOI: 10.1093/annonc/mdz111 -
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