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Frontiers in Bioscience (Landmark... Jun 2016Heparin, a sulfated polysaccharide, has been used as a clinical anticoagulant for over 90 years. Newer anticoagulants, introduced for certain specialized applications,... (Review)
Review
Heparin, a sulfated polysaccharide, has been used as a clinical anticoagulant for over 90 years. Newer anticoagulants, introduced for certain specialized applications, have not significantly displaced heparin and newer heparin-based anticoagulants in most medical procedures. This chapter, while reviewing anticoagulation and these newer anticoagulants, focuses on heparin-based anticoagulants, including unfractionated heparin, low molecular weight heparins and ultra-low molecular weight heparins. Heparin's structures and its biological and therapeutic roles are discussed. Particular emphasis is placed on heparin's therapeutic application and its adverse effects. The future prospects are excellent for new heparins and new heparin-based therapeutics with improved properties.
Topics: Anticoagulants; Blood Coagulation; Disseminated Intravascular Coagulation; Extracorporeal Circulation; Heparin; Humans; Venous Thromboembolism
PubMed: 27100512
DOI: 10.2741/4462 -
Journal of Thrombosis and Thrombolysis Jan 2016Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the... (Review)
Review
Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.
Topics: Anticoagulants; Heparin; Humans; Practice Guidelines as Topic; Venous Thromboembolism
PubMed: 26780745
DOI: 10.1007/s11239-015-1315-2 -
Applied Microbiology and Biotechnology Oct 2018Heparin is a highly sulfated polysaccharide which belongs to the family of glycosaminoglycans. It is involved in various important biological activities. The major... (Review)
Review
Heparin is a highly sulfated polysaccharide which belongs to the family of glycosaminoglycans. It is involved in various important biological activities. The major biological purpose is the inhibition of the coagulation cascade to maintain the blood flow in the vasculature. These properties are employed in several therapeutic drugs. Heparin's activities are associated with its interaction to various proteins. To date, the structural heparin-protein interactions are not completely understood. This review gives a general overview of specific patterns and functional groups which are involved in the heparin-protein binding. An understanding of the heparin-protein interactions at the molecular level is not only advantageous in the therapeutic application but also in biotechnological application of heparin for downstreaming. This review focuses on the heparin affinity chromatography. Diverse recombinant proteins can be successfully purified by this method. While effective, it is disadvantageous that heparin is an animal-derived material. Animal-based components carry the risk of contamination. Therefore, they are liable to strict quality controls and the validation of effective good manufacturing practice (GMP) implementation. Hence, adequate alternatives to animal-derived components are needed. This review examines strategies to avoid these disadvantages. Thereby, alternatives for the provision of heparin such as chemical synthesized heparin, chemoenzymatic heparin, and bioengineered heparin are discussed. Moreover, the usage of other chromatographic systems mimetic the heparin effect is reviewed.
Topics: Animals; Chromatography, Affinity; Heparin; Humans; Proteins
PubMed: 30094590
DOI: 10.1007/s00253-018-9263-3 -
International Journal of Molecular... Sep 2021Heparin has been extensively studied as a safe medicine and biomolecule over the past few decades. Heparin derivatives, including low-molecular-weight heparins (LMWH)... (Review)
Review
Heparin has been extensively studied as a safe medicine and biomolecule over the past few decades. Heparin derivatives, including low-molecular-weight heparins (LMWH) and heparin pentasaccharide, are effective anticoagulants currently used in clinical settings. They have also been studied as functional biomolecules or biomaterials for various therapeutic uses to treat diseases. Heparin, which has a similar molecular structure to heparan sulfate, can be used as a remarkable biomedicine due to its uniquely high safety and biocompatibility. In particular, it has recently drawn attention for use in drug-delivery systems, biomaterial-based tissue engineering, nanoformulations, and new drug-development systems through molecular formulas. A variety of new heparin-based biomolecules and conjugates have been developed in recent years and are currently being evaluated for use in clinical applications. This article reviews heparin derivatives recently studied in the field of drug development for the treatment of various diseases.
Topics: Anticoagulants; Biocompatible Materials; Drug Delivery Systems; Heparin, Low-Molecular-Weight; Humans; Tissue Engineering
PubMed: 34638867
DOI: 10.3390/ijms221910524 -
Critical Care (London, England) Jan 2017Heparin saline (HS) is theoretically superior to normal saline (NS) for maintaining the patency of central venous catheters (CVCs), but the comparative efficacy of them... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heparin saline (HS) is theoretically superior to normal saline (NS) for maintaining the patency of central venous catheters (CVCs), but the comparative efficacy of them remains controversial. The aim of this systematic review and meta-analysis was to assess the efficacy of NS versus HS in the maintenance of the patency of CVCs in adult patients.
METHODS
We searched PubMed, Embase and the Cochrane library databases. Randomized controlled trials (RCTs) evaluating the use of NS vs. HS to maintain the permeability of CVCs among adult patients were included in our meta-analysis. References of relevant papers were reviewed manually. No language restriction was applied. Non-human studies were excluded. Pooled relative risk (RR) was calculated using a Mantel-Haenszel random-effects model. We also performed subgroup analysis examining the effect of the duration of catheter placement on the outcome. All statistical tests were two-sided using a significance level of 0.05.
RESULTS
Ten RCTs involving 7875 subjects (with analysis at patient, catheter, lumen and line access level) were included in this meta-analysis. Whether in terms of pooled or local analysis (RR with 95% confidence interval spans 1), NS can be equally, if not more effective, in keeping the CVCs open. Of studies reporting secondary outcomes (maneuver needed, heparin-induced thrombocytopenia, haemorrhage, central venous thrombosis and catheter-related bloodstream infection), heparinised saline was shown not to be superior to non-heparinised solution. Subgroup analysis in patients with short vs long term CVC placement was consistent with the main outcome partly and in particular for maintenance of catheter patency in patients with a long-term placement i.e. >30 days, the RR was 0.97 (n = 6589; 95% CI = 0.76 to 1.23; P = 0.796). However, for patients in whom the catheter was in place for <30 days, the RR was 1.52 (n = 1286; 95% CI = 1.02 to 2.27; P = 0.041).
CONCLUSIONS
Based on the results of this meta-analysis, HS is not superior to NS in reducing CVCs occlusion. But in the short term, the use of HS is slightly superior to NS for flushing catheters from a statistical point of view.
Topics: Adult; Catheter Obstruction; Central Venous Catheters; Heparin; Humans; Sodium Chloride; Therapeutic Irrigation; Thrombosis
PubMed: 28063456
DOI: 10.1186/s13054-016-1585-x -
Viruses Dec 2021Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific... (Review)
Review
Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific ability, as with other oligosaccharides and glycosaminoglycan, to bind several types of viruses during their pass through the extracellular matrix of the respiratory tract, as well as its anticoagulant activity to prevent venous thromboembolism. Antithrombotic actions of enoxaparin have been testified both for inpatients with COVID-19 in regular ward and for inpatients in Intensive Care Units (ICUs). Prophylactic doses seem to be able to prevent venous thromboembolism (VTE) in inpatients in the regular ward, while intermediate or therapeutic doses have been frequently adopted for inpatients with COVID-19 in ICU. On the other hand, although we reported several useful actions of heparin for inpatients with COVID-19, an increased rate of bleeding has been recorded, and it may be related to several conditions such as underlying diseases with increased risks of bleeding, increased doses or prolonged administration of heparin, personal trend to bleed, and so on.
Topics: Anticoagulants; COVID-19; Enoxaparin; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Inpatients; Intensive Care Units; Pandemics; SARS-CoV-2; Venous Thromboembolism
PubMed: 34960754
DOI: 10.3390/v13122486 -
Indian Journal of Dermatology,... 2016Anticoagulants are the cornerstone of treatment of venous thromboembolism associated with various medical conditions and surgical procedures. They act on different steps... (Review)
Review
Anticoagulants are the cornerstone of treatment of venous thromboembolism associated with various medical conditions and surgical procedures. They act on different steps of the coagulation pathway and are broadly categorized into heparins, vitamin K antagonists, and inhibitors of thrombin and factor Xa. The classification is evolving as newer and better oral and parenteral anticoagulants are being added. Anticoagulants in dermatology are important not only for their therapeutic application in cutaneous thrombotic dermatoses such as livedoid vasculitis, purpura fulminans, superficial and deep venous thrombosis and others but also for their use in non-thrombotic dermatoses such as lichen planus, recurrent oral aphthosis, chronic urticaria and several others. Further, the use of anticoagulants for any indication is associated with various adverse effects with dermatologic manifestations including specific reactions such as warfarin-induced skin necrosis, heparin-induced thrombocytopenia and anticoagulant-associated cholesterol embolization syndrome.
Topics: Anticoagulants; Dermatology; Heparin; Humans; Skin Diseases; Thromboembolism; Venous Thrombosis; Warfarin
PubMed: 27320765
DOI: 10.4103/0378-6323.184199 -
International Journal of Molecular... Oct 2019Anticoagulant agents are widely used in the treatment of thromboembolic events and in stroke prevention. Data about their effects on bone tissue are in some cases... (Review)
Review
Anticoagulant agents are widely used in the treatment of thromboembolic events and in stroke prevention. Data about their effects on bone tissue are in some cases limited or inconsistent (oral anti-vitamin K agents), and in others are sufficiently strong (heparins) to suggest caution in their use in subjects at risk of osteoporosis. This review analyses the effects of this group of drugs on bone metabolism, on bone mineral density, and on fragility fractures. A literature search strategy was developed by an experienced team of specialists by consulting the MEDLINE platform, including published papers and reviews updated to March 2019. Literature supports a detrimental effect of heparin on bone, with an increase in fracture rate. Low molecular weight heparins (LMWHs) seem to be safer than heparin. Although anti-vitamin K agents (VKAs) have a significant impact on bone metabolism, and in particular, on osteocalcin, data on bone mineral density (BMD) and fractures are contrasting. To date, the new direct oral anticoagulants (DOACs) are found to safe for bone health.
Topics: Anticoagulants; Bone Density; Bone and Bones; Fractures, Bone; Heparin, Low-Molecular-Weight; Humans; Osteoporosis; Venous Thromboembolism
PubMed: 31652944
DOI: 10.3390/ijms20215275 -
Analytical and Bioanalytical Chemistry Jan 2011
Topics: Animals; Anticoagulants; Drug Contamination; Heparin; Swine
PubMed: 21116617
DOI: 10.1007/s00216-010-4437-6