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Blood Advances Nov 2018Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction mediated by platelet-activating antibodies that target complexes of platelet factor 4 and heparin....
BACKGROUND
Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction mediated by platelet-activating antibodies that target complexes of platelet factor 4 and heparin. Patients are at markedly increased risk of thromboembolism.
OBJECTIVE
These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about diagnosis and management of HIT.
METHODS
ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.
RESULTS
The panel agreed on 33 recommendations. The recommendations address screening of asymptomatic patients for HIT, diagnosis and initial management of patients with suspected HIT, treatment of acute HIT, and special situations in patients with acute HIT or a history of HIT, including cardiovascular surgery, percutaneous cardiovascular intervention, renal replacement therapy, and venous thromboembolism prophylaxis.
CONCLUSIONS
Strong recommendations include use of the 4Ts score rather than a gestalt approach for estimating the pretest probability of HIT and avoidance of HIT laboratory testing and empiric treatment of HIT in patients with a low-probability 4Ts score. Conditional recommendations include the choice among non-heparin anticoagulants (argatroban, bivalirudin, danaparoid, fondaparinux, direct oral anticoagulants) for treatment of acute HIT.
Topics: Administration, Oral; Anticoagulants; Arginine; Cardiovascular Surgical Procedures; Chondroitin Sulfates; Dermatan Sulfate; Evidence-Based Medicine; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Count; Recombinant Proteins; Renal Replacement Therapy; Sulfonamides; Thrombocytopenia; Venous Thromboembolism
PubMed: 30482768
DOI: 10.1182/bloodadvances.2018024489 -
Pharmaceuticals (Basel, Switzerland) Feb 2018In this editorial to MDPI special issue "" we describe in outline the common structural features of glycosaminoglycans and the characteristics of proteoglycans,...
In this editorial to MDPI special issue "" we describe in outline the common structural features of glycosaminoglycans and the characteristics of proteoglycans, including the intracellular proteoglycan, serglycin, cell-surface proteoglycans, like syndecans and glypicans, and the extracellular matrix proteoglycans, like aggrecan, perlecan, and small leucine-rich proteoglycans. The context in which the pharmaceutical uses of glycosaminoglycans and proteoglycans are presented in this special issue is given at the very end.
PubMed: 29495527
DOI: 10.3390/ph11010027 -
American Journal of Physiology. Cell... Jun 2022Glycosaminoglycans (GAGs) are complex linear polysaccharides, which are covalently attached to core proteins (except for hyaluronan) to form proteoglycans. They play key... (Review)
Review
Glycosaminoglycans (GAGs) are complex linear polysaccharides, which are covalently attached to core proteins (except for hyaluronan) to form proteoglycans. They play key roles in the organization of the extracellular matrix, and at the cell surface where they contribute to the regulation of cell signaling and of cell adhesion. To explore the mechanisms and pathways underlying their functions, we have generated an expanded dataset of 4,290 interactions corresponding to 3,464 unique GAG-binding proteins, four times more than the first version of the GAG interactome (Vallet, Clerc, and Ricard-Blum. 69: 93-104, 2021). The increased size of the GAG network is mostly due to the addition of GAG-binding proteins captured from cell lysates and biological fluids by affinity chromatography and identified by mass spectrometry. We review here the interaction repertoire of natural GAGs and of synthetic sulfated hyaluronan, the specificity and molecular functions of GAG-binding proteins, and the biological processes and pathways they are involved in. This dataset is also used to investigate the differences between proteins binding to iduronic acid-containing GAGs (dermatan sulfate and heparin/heparan sulfate) and those interacting with GAGs lacking iduronic acid (chondroitin sulfate, hyaluronan, and keratan sulfate).
Topics: Glycosaminoglycans; Heparitin Sulfate; Hyaluronic Acid; Iduronic Acid; Proteoglycans
PubMed: 35544698
DOI: 10.1152/ajpcell.00095.2022 -
Glycoconjugate Journal Jun 2017Mast cells contain granules packed with a mixture of proteins that are released on degranulation. The proteoglycan serglycin carries an array of glycosaminoglycan (GAG)... (Review)
Review
Mast cells contain granules packed with a mixture of proteins that are released on degranulation. The proteoglycan serglycin carries an array of glycosaminoglycan (GAG) side chains, sometimes heparin, sometimes chondroitin or dermatan sulphate. Tight packing of granule proteins is dependent on the presence of serglycin carrying these GAGs. The GAGs of mast cells were most intensively studied in the 1970s and 1980s, and though something is known about the fine structure of chondroitin sulphate and dermatan sulphate in mast cells, little is understood about the composition of the heparin/heparan sulphate chains. Recent emphasis on the analysis of mast cell heparin from different species and tissues, arising from the use of this GAG in medicine, lead to the question of whether variations within heparin structures between mast cell populations are as significant as variations in the mix of chondroitins and heparins.
Topics: Animals; Carbohydrate Conformation; Carbohydrate Sequence; Cell Degranulation; Cells, Cultured; Chondroitin Sulfates; Cytoplasmic Granules; Dermatan Sulfate; Heparin; Humans; Mast Cells; Peptide Hydrolases; Protein Binding; Proteoglycans; Structure-Activity Relationship; Vesicular Transport Proteins
PubMed: 27900574
DOI: 10.1007/s10719-016-9749-0 -
Advances in Experimental Medicine and... 2017Glycosaminoglycans (GAGs) are important constituents of the extracellular matrix that make significant contributions to biological processes and have been implicated in... (Review)
Review
Glycosaminoglycans (GAGs) are important constituents of the extracellular matrix that make significant contributions to biological processes and have been implicated in a wide variety of diseases. GAG-degrading enzymes with different activities have been found in various animals and microorganisms, and they play an irreplaceable role in the structure and function studies of GAGs. As two kind of important GAG-degrading enzymes, hyaluronidase (HAase) and chondroitinase (CSase) have been widely studied and increasing evidence has shown that, in most cases, their substrate specificities overlap and thus the "HAase" or "CSase" terms may be improper or even misnomers. Different from previous reviews, this article combines HAase and CSase together to discuss the traditional classification, substrate specificity, degradation pattern, new resources and naming of these enzymes.
Topics: Animals; Bacteria; Carbohydrate Conformation; Carbohydrate Sequence; Chondroitinases and Chondroitin Lyases; Eukaryotic Cells; Extracellular Matrix; Glycosaminoglycans; Humans; Hyaluronoglucosaminidase; Hydrolysis; Kinetics; Substrate Specificity; Viruses
PubMed: 27677277
DOI: 10.1007/5584_2016_54 -
Current Opinion in Structural Biology Jun 2018Glycosaminoglycans (GAGs) interact with a variety of proteins with important functions in development and homeostasis. Most of these proteins bind to heparin in vitro, a... (Review)
Review
Glycosaminoglycans (GAGs) interact with a variety of proteins with important functions in development and homeostasis. Most of these proteins bind to heparin in vitro, a highly sulfated GAG species, although heparan sulfate and/or chondroitin/dermatan sulfate are more frequent physiological ligands. Binding affinity and specificity are determined by charge distribution, mainly due to sulfate and carboxylate groups and by GAG chain conformation. Interactions may be nonspecific, essentially reflecting charge density or highly specific, dependent on rare GAG-structural features. Yet other GAG epitopes bind protein ligands with intermediate specificity and variable affinity. Studies of heparan sulfate biosynthesis point to stochastic but strictly regulated, cell-specific polymer modification. Together, these features allow for graded modulation of protein functional response.
Topics: Glycosaminoglycans; Models, Molecular; Molecular Conformation; Protein Binding; Proteins; Structure-Activity Relationship
PubMed: 29455055
DOI: 10.1016/j.sbi.2017.12.011 -
Postgraduate Medical Journal Aug 2018Heparin-induced thrombocytopaenia (HIT) is a severe and potentially life-threatening adverse drug reaction. Patients become extremely hypercoagulable, and this can lead... (Review)
Review
Heparin-induced thrombocytopaenia (HIT) is a severe and potentially life-threatening adverse drug reaction. Patients become extremely hypercoagulable, and this can lead to life-threatening and limb-threatening thrombosis with a mortality of 5%-10%. HIT is an antibody-mediated process in which platelet activation occurs. Diagnosis requires a high index of suspicion along with a scoring system and laboratory testing. Patients suspected of having HIT must not receive any further heparin or low-molecular weight heparin and must be started on an alternative anticoagulant such as argatroban or danaparoid. Fondaparinux may also be considered but is not licenced for this indication.
Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Fondaparinux; Heparin; Heparitin Sulfate; Humans; Pipecolic Acids; Polysaccharides; Sulfonamides; Thrombocytopenia
PubMed: 30126928
DOI: 10.1136/postgradmedj-2018-135702