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Seminars in Thrombosis and Hemostasis Nov 2020Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching...
Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching epidemic proportions worldwide, the optimal dosage for obese patients has not been established for most anticoagulants, including low-molecular-weight heparin (LMWH), non-vitamin K antagonist oral anticoagulants (NOAC), and pentasaccharides (fondaparinux). The aim of the present systematic review was to summarize the current knowledge and provide recommendations on dosage of LMWH, NOAC, and fondaparinux in obese patients (body mass index [BMI] ≥ 30 kg/m or body weight ≥ 100 kg). Based on a systematic search in PubMed and Embase, a total of 72 studies were identified. For thromboprophylaxis with LMWH in bariatric surgery ( = 20 studies), enoxaparin 40 mg twice daily, dalteparin 5,000 IE twice daily, or tinzaparin 75 IU/kg once daily should be considered for patients with BMI ≥ 40 kg/m. For thromboprophylaxis with LMWH in nonbariatric surgery and in medical inpatients ( = 8 studies), enoxaparin 0.5 mg/kg once or twice daily or tinzaparin 75 IU/kg once daily may be considered in obese patients. For treatment with LMWH ( = 18 studies), a reduced weight-based dose of enoxaparin 0.8 mg/kg twice daily should be considered in patients with BMI ≥ 40 kg/m, and no dose capping of dalteparin and tinzaparin should be applied for body weight < 140 kg. As regards NOAC, rivaroxaban, apixaban, or dabigatran may be used as thromboprophylaxis in patients with BMI < 40 kg/m ( = 4 studies), whereas rivaroxaban and apixaban may be administered to obese patients with VTE or AF, including BMI > 40 kg/m, at standard fixed-dose ( = 20 studies). The limited available evidence on fondaparinux ( = 3 studies) indicated that the treatment dose should be increased to 10 mg once daily in patients weighing > 100 kg.
Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Obesity
PubMed: 33368113
DOI: 10.1055/s-0040-1718405 -
Clinical and Applied... Jul 2018Current guidelines recommend low-molecular-weight heparin treatment in patients with cancer with established venous thromboembolism (VTE). The aim of this article was to... (Review)
Review
Current guidelines recommend low-molecular-weight heparin treatment in patients with cancer with established venous thromboembolism (VTE). The aim of this article was to study the pharmacological properties and effectiveness of tinzaparin in patients with cancer as well as its potential anticancer properties. A search of PubMed and ScienceDirect databases up to March 2016 was carried out to identify published studies that detect the properties and use of tinzaparin in oncology. Protamine sulfate partially (60% to 65%) neutralized tinzaparin's anti-Xa activity. No dose adjustment of tinzaparin is needed even in patients with severe renal impairment and Creatinine Clearance ≥20 mL/min. Tinzaparin demonstrated a statistically significant decline in VTE recurrence at 1 year post the index thromboembolic event. A statistically significant reduction in minor bleeding rates was also described, whereas major bleeding events did not decrease in patients with cancer treated with tinzaparin versus those who received vitamin K antagonists. Tinzaparin treatment in patients suffering from deep vein thrombosis reduced the incidence of postthrombotic syndrome and venous ulcers. Tinzaparin's ability to prevent both metastatic dissemination of cancer cells and tumor angiogenesis has been delineated in preclinical research. Current data show that tinzaparin is safe and efficacious either for short-term or for long-term treatment of VTE in patients with cancer. Clinical trials are needed in order to examine the utility of tinzaparin in primary prevention of VTE and validate its potential anticancer advantages exhibited in preclinical research.
Topics: Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Tinzaparin; Treatment Outcome; Venous Thromboembolism
PubMed: 29088922
DOI: 10.1177/1076029617729215 -
European Journal of Clinical... Oct 2022Low molecular weight heparins (LMWHs) are a group of heterogenous moieties, long used in the prevention and treatment of thrombosis. They derive from heparin and since... (Review)
Review
PURPOSE
Low molecular weight heparins (LMWHs) are a group of heterogenous moieties, long used in the prevention and treatment of thrombosis. They derive from heparin and since they are prepared by different methods of depolymerization, they differ in pharmacokinetic properties and anticoagulant profiles, and thus are not clinically interchangeable.
METHODS
In this review we provide an overview of tinzaparin's main characteristics and uses.
RESULTS
Tinzaparin which is produced by the enzymatic depolymerization of unfractionated heparin (UFH) can be used for the treatment and prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE); it has been also used in special populations such as elders, obese, pregnant women, and patients with renal impairment and/or cancer with favorable outcomes in both safety and efficacy, with a once daily dose regimen. Furthermore, LMWHs are extensively used in clinical practice for both thromboprophylaxis and thrombosis treatment of COVID-19 patients.
CONCLUSION
Tinzaparin features support the hypothesis for having a role in immunothrombosis treatment (i.e. in the context of cancer ,COVID-19), interfering not only with coagulation cascade but also exhibiting anti-inflammatory potency.
Topics: Aged; Anticoagulants; COVID-19; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Thrombosis; Tinzaparin; Venous Thromboembolism
PubMed: 35871241
DOI: 10.1007/s00228-022-03365-4 -
Neurology International May 2021An outbreak of African swine fever (ASF) in China in 2020 has led to an unprecedented shortage of nadroparin. Most patients, especially those kept in hospital for...
BACKGROUND
An outbreak of African swine fever (ASF) in China in 2020 has led to an unprecedented shortage of nadroparin. Most patients, especially those kept in hospital for surgery, are currently treated with prophylactic anticoagulation (AC). In search of alternatives for nadroparin (fraxiparine), we found no sufficient data on alternatives for neurosurgical patients, such as tinzaparin of European origin. We compared nadroparin and tinzaparin concerning adverse events (bleeding versus thromboembolic events) in neurosurgical patients.
METHODS
Between 2012 and 2018, 517 neurosurgical patients with benign and malignant brain tumors as well as 297 patients with subarachnoid hemorrhage (SAH) were treated in the Department of Neurosurgery, University Hospital Leipzig, receiving prophylactic anticoagulation within 48 h. In 2015, prophylactic anticoagulation was switched from nadroparin to tinzaparin throughout the university hospital. In a retrospective manner, the frequency and occurrence of adverse events (rebleeding and thromboembolic events) in connection with the substance used were analyzed. Statistical analysis was performed using Fisher's exact test and the chi-squared test.
RESULTS
Rebleeding rates were similar in both nadroparin and tinzaparin cohorts in patients being treated for meningioma, glioma, and SAH combined (8.8% vs. 10.3%). Accordingly, the rates of overall thromboembolic events were not significantly different (5.5% vs. 4.3%). The severity of rebleeding did not vary. There was no significant difference among subgroups when compared for deep vein thrombosis (DVT) or pulmonary embolism (PE).
CONCLUSION
In this retrospective study, tinzaparin seems to be a safe alternative to nadroparin for AC in patients undergoing brain tumor surgery or suffering from SAH.
PubMed: 34067998
DOI: 10.3390/neurolint13020021 -
Biochimie Jul 2022Heparinases are enzymes that selectively cleave heparin and heparan sulfate chains, via cleavage of the glycosidic linkage between hexosamines and uronic acids,... (Review)
Review
Heparinases are enzymes that selectively cleave heparin and heparan sulfate chains, via cleavage of the glycosidic linkage between hexosamines and uronic acids, producing disaccharide and oligosaccharide products. While heparin is well known as an anti-coagulant drug, heparin and heparan sulfate are also involved in biological processes such as inflammation, cancer and angiogenesis and viral and bacterial infections and are of growing interest for their therapeutic potential. Recently, potential roles of heparin and heparan sulfate in relation to COVID-19 infection have been highlighted. The ability of heparinases to selectively cleave heparin chains has been exploited industrially to produce low molecular weight heparin, which has replaced heparin in several clinical applications. Other applications of heparinases include heparin and heparan sulfate structural analysis, neutralisation of heparin in blood and removal of the inhibitory effect of heparin on various enzymes. Heparinases are known to inhibit neovascularization and heparinase III is of interest for treating cancer and inhibiting tumour cell growth. Heparinase activity, first isolated from Pedobacter heparinus, has since been reported from several other microorganisms. Significant progress has been made in the production, characterisation and improvement of microbial heparinases in response to application demands in terms of heparinase yield and purity, which is likely to extend their usefulness in various applications. This review focuses on recent developments in the identification, characterisation and improvement of microbial heparinases and their established and emerging industrial, clinical and therapeutic applications.
Topics: COVID-19; Heparin; Heparin Lyase; Heparitin Sulfate; Humans; Oligosaccharides
PubMed: 35367577
DOI: 10.1016/j.biochi.2022.03.011 -
Oncology Reports Nov 2021Tinzaparin is an anticoagulant and antiangiogenic drug with inhibitory properties against tumor growth. VEGF stimulates angiogenesis, while an association between...
Tinzaparin inhibits VL30 retrotransposition induced by oxidative stress and/or VEGF in HC11 mouse progenitor mammary cells: Association between inhibition of cancer stem cell proliferation and mammosphere disaggregation.
Tinzaparin is an anticoagulant and antiangiogenic drug with inhibitory properties against tumor growth. VEGF stimulates angiogenesis, while an association between reactive oxygen species (ROS) and angiogenesis is involved in tumor progression. The present study aimed to investigate the effect of tinzaparin on VL30 retrotransposition‑positive mouse HC11 mammary stem‑like epithelial cells, previously reported to be associated with induced mammosphere/cancer stem cell (CSC) generation and tumorigenesis. Under 24 h serum starvation, 15.2% nominal retrotransposition frequency was increased to 29%. Additionally, while treatment with 3‑12 ng/ml VEGF further induced retrotransposition frequency in a dose‑dependent manner (up to 40.3%), pre‑incubation with tinzaparin (2 IU/ml) for 0.5‑4 h reduced this frequency to 18.3% in a time‑dependent manner, confirmed by analogous results in NIH3T3 fibroblasts. Treatment with 10‑40 pg/ml glucose oxidase (GO) for 24 h induced HC11 cell retrotransposition in a dose‑dependent manner (up to 82.5%), while a 3 h pre‑incubation with tinzaparin (1 or 2 IU/ml) elicited a 13.5 or 25.5% reduction in retrotransposition, respectively. Regarding tumorigenic VL30 retrotransposition‑positive HC11 cells, treatment with 2 IU/ml tinzaparin for 5 days reduced proliferation rate in a time‑dependent manner (up to ~55%), and after 3 weeks, disaggregated soft agar‑formed foci, as well as low‑adherent mammospheres, producing single mesenchymal‑like cells with a ~50% reduced retrotransposition. With respect to the VL30 retrotransposition mechanism: While 12 ng/ml VEGF increased the level of VL30 and endogenous reverse transcriptase (enRT) transcripts ~1.41‑ and ~1.16‑fold, respectively, subsequent tinzaparin treatment reduced both endogenous/ROS‑ and VEGF‑induced levels 1.15‑ and 0.40‑fold (VL30) and 0.60‑ and 0.52‑fold (enRT), respectively. To the best of our knowledge, these data demonstrate for the first time, the novel inhibition activity of tinzaparin against ROS‑ and VEGF‑induced VL30 retrotransposition, and the proliferation and/or aggregation of mouse HC11 mammosphere/tumor‑initiating CSCs, thus contributing to the inhibition of VL30 retrotransposition‑induced primary tumor growth.
Topics: Animals; Anticoagulants; Cell Proliferation; Cells, Cultured; Female; Mice; Mice, Inbred BALB C; NIH 3T3 Cells; Neoplastic Stem Cells; Oxidative Stress; Tinzaparin; Vascular Endothelial Growth Factor A
PubMed: 34558648
DOI: 10.3892/or.2021.8192