NationMaster - Encyclopedia: Heparin

Heparin, a highly sulfated glycosaminoglycan is widely used as an injectable anticoagulant and has the highest negative charge density of any known biological molecule.^[1] It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and renal dialysis machines. Pharmaceutical grade heparin is commonly derived from mucosal tissues of slaughtered meat animals such as porcine intestine or bovine lung.^[2] In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... Chondroitin sulfate Hyaluronan Glycosaminoglycans (GAGs) or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ... Charge density is the amount of electric charge per unit volume. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... A test tube (Sometimes culture tube) is a kind of laboratory glassware, composed of a fingerlike length of glass tubing, open at the top, sometimes with a rounded lip at the top, and a rounded U shaped bottom. ... This article is about clinical dialysis; for the laboratory technique, see Dialysis (biochemistry) In medicine, dialysis is a method for removing waste such as urea from the blood when the kidneys are incapable of this, i. ... The mucous membranes (or mucosae; singular: mucosa) are linings of ectodermic origin, covered in epithelium, and are involved in absorption and secretion. ... For the Batman villain, see Abattoir (comics). ...

Heparin structure

Native heparin is a polymer with a molecular weight ranging from 3 kDa to 40 kDa although the average molecular weight of most commercial heparin preparations is in the range of 12 kDa to 15 kDa. Heparin is a member of the glycosaminoglycan family of carbohydrates (which includes the closely related molecule heparan sulfate) and consists of a variably sulfated repeating disaccharide unit. The main disaccharide units that occur in heparin are shown below. The most common disaccharide unit is composed of a 2-O-sulfated iduronic acid and 6-O-sulfated, N-sulfated glucosamine, IdoA(2S)-GlcNS(6S). For example this makes up 85% of heparins from beef lung and about 75% of those from porcine intestinal mucosa.^[3] Not shown below are the rare disaccharides containing a 3-O-sulfated glucosamine (GlcNS(3S,6S)) or a free amine group (GlcNH₃⁺). Under physiological conditions the ester and amide sulfate groups are deprotonated and attract positively charged counterions to form a heparin salt. It is in this form that heparin is usually administered as an anticoagulant. The unified atomic mass unit (u), or dalton (Da), is a small unit of mass used to express atomic and molecular masses. ... Chondroitin sulfate Hyaluronan Glycosaminoglycans (GAGs) or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. ... Carbohydrates (literally hydrates of carbon) are chemical compounds that act as the primary biological means of storing or consuming energy, other forms being fat and protein. ... Heparan Sulfate (HS) is a linear polysaccharide found in all animal tissues. ... Sucrose, a common disaccharide A disaccharide is a sugar (a carbohydrate) composed of two monosaccharides. ... A carboxylic acid ester. ... Amide functional group Amides possess a conjugated system spread over the O, C and N atoms, consisting of molecular orbitals occupied by delocalized electrons. ...

1 unit of heparin is the quantity of heparin required to keep 1 mL of cat's blood fluid for 24 hours at 0°C; it is equivalent approximately to 0.002 mg of pure heparin.

Image File history File links GlcA-GlcNAc. ... Image File history File links GlcA-GlcNS.pngâ€Ž Licensing I, the creator of this work, hereby release it into the public domain. ... Image File history File links IdoA-GlcNS.pngâ€Ž Licensing I, the creator of this work, hereby release it into the public domain. ... Image File history File links IdoA(2S)-GlcNS.pngâ€Ž Licensing I, the creator of this work, hereby release it into the public domain. ... Image File history File links IdoA-GlcNS(6S). ... Image File history File links IdoA(2S)-GlcNS(6S). ...

Abbreviations

The Î±-D form of glucuronic acid. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ...

Three-dimensional structure

The three dimensional structure of heparin is complicated by the fact that iduronic acid may be present in either of two low energy conformations when internally positioned within an oligosaccharide. The conformational equilibrium being influenced by sulfation state of adjacent glucosamine sugars.^[4] Nevertheless the solution structure of a heparin dodecasacchride composed solely of six GlcNS(6S)-IdoA(2S) repeat units has been determined using a combination of NMR spectroscopy and molecular modelling techniques.^[5] Two models were constructed one in which all IdoA(2S) were in the ²S₀ conformation (A and B below) and one in which they are in the ¹C₄ conformation (C and D below). However there is no evidence to suggest changes between these conformations occurs in a concerted fashion. These models correspond to the protein data bank code 1HPN. The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ...

In the image above: Image File history File links Download high-resolution version (1100x977, 484 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Heparin ...

In these models heparin adopts a helical conformation, the rotation of which places clusters of sulfate groups at regular intervals of about 17 angstroms (1.7 nm) on either side of the helical axis. The van der Waals radius of an atom is the radius of an imaginary hard sphere which can be used to model the atom for many purposes. ... An angstrom, angstrÃ¶m, or Ã¥ngstrÃ¶m (symbol Ã…) is a unit of length. ... A nanometre (American spelling: nanometer) is 1. ...

Medical use

Heparin is a naturally occurring anticoagulant produced by basophils and mast cells.^[6] Heparin acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. While heparin does not break down clots that have already formed (tissue plasminogen activator will), it allows the body's natural clot lysis mechanisms to work normally to break down clots that have already formed. Heparin is used for anticoagulation for the following conditions: Categories: Wikipedia cleanup | Biology stubs | Blood and immune system cells ... Mast cells A mast cell (or mastocyte) is a resident cell of areolar connective tissue (loose connective tissue) that contains many granules rich in histamine and heparin. ... In blood coagulation, tissue plasminogen activator (tPA) is an enzyme (EC 3. ...

An acute coronary syndrome (ACS) is a set of signs and symptoms suggestive of sudden cardiac ischemia, usually caused by disruption of atherosclerotic plaque in an epicardial coronary artery. ... Acute myocardial infarction (AMI or MI), more commonly known as a heart attack, is a disease state that occurs when the blood supply to a part of the heart is interrupted. ... Atrial fibrillation (AF or afib) is a cardiac arrhythmia (abnormal heart rhythm) that involves the two upper chambers (atria) of the heart. ... DVT can also refer to Driving Van Trailer Deep venous thrombosis (or DVT) is the occlusion of a deep vein by a blood clot (thrombus). It generally affects the leg veins, such as the femoral vein or the popliteal vein, or occasionally the veins of the arm (Paget-von Schroetter... A Heart-Lung Machine (upper right) in a Coronary Artery Bypass surgery (CABG) Cardiopulmonary bypass (CPB) is a technique that temporarily takes over the function of the heart and lungs during surgery. ... Cardiac surgery is surgery on the heart, typically to correct congenital heart disease or the complications of ischaemic heart disease or valve problems caused by endocarditis. ...

Administration

Details of administration are available in clinical practice guidelines by the American College of Chest Physicians^[7]: A medical guideline (also called a clinical guideline, clinical protocol or clinical practice guideline) is a document with the aim of guiding decisions and criteria in specific areas of healthcare, as defined by an authoritative examination of current evidence (evidence-based medicine). ... The American College of Chest Physicians (ACCP) is a medical organization consisting of physicians and non-physician specialists in the field of chest medicine, which includes pulmonology, thoracic surgery, and intensive care medicine. ...

Heparin is given parenterally, as it is degraded when taken by mouth. It can be injected intravenously or subcutaneously (under the skin). Intramuscular injections (into muscle) are avoided because of the potential for forming hematomas. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Hematoma on thigh after a beating. ...

Because of its short biologic half-life of approximately one hour, heparin must be given frequently or as a continuous infusion. However the use of low molecular weight heparin (LMWH) has allowed once daily dosing, thus not requiring a continuous infusion of the drug. If long-term anticoagulation is required, heparin is often only used to commence anticoagulation therapy until the oral anticoagulant warfarin takes effect. Half-Life For a quantity subject to exponential decay, the half-life is the time required for the quantity to fall to half of its initial value. ... An infusion is a beverage made by steeping a flavoring substance in hot or boiling water. ... In medicine, low molecular weight heparin (LMWH) is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis. ... Warfarin (also known under the brand names of Coumadin, Jantoven, Marevan, and Waran) is an anticoagulant medication that is administered orally or, very rarely, by injection. ...

Adverse reactions

A serious side-effect of heparin is heparin-induced thrombocytopenia (HIT syndrome). HITS is caused by an immunological reaction that makes platelets aggregate within the blood vessels, thereby using up coagulation factors. Formation of platelet clots can lead to thrombosis, while the loss of coagulation factors and platelets may result in bleeding. HITS can (rarely) occur shortly after heparin is given, but also when a person has been on heparin for a long while. Immunologic tests are available for the diagnosis of HITS. There is also a benign form of thrombocytopenia associated with early heparin use which resolves without stopping heparin. Heparin-induced thrombocytopenia (HIT) with or without thrombosis (HITT) is thrombocytopenia (low platelet counts) due to the administration of heparin. ...

Rarer side effects include alopecia and osteoporosis with chronic use. Alopecia is a set of disorders ranging from male and female pattern alopecia (alopecia androgenetica), to alopecia areata, which involves the loss of some of the hair from the head, alopecia totalis, which involves the loss of all head hair, to the most extreme form, alopecia universalis, which involves the... Osteoporosis is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. ...

As with many drugs, overdoses of heparin can be fatal. In September 2006, heparin received worldwide publicity when 3 prematurely-born infants died after they were mistakenly given overdoses of heparin at an Indianapolis hospital.^[8]

Treatment of overdose

In case of overdose, protamine sulfate can be given to counteract the action of heparin, in the same amount as heparin. Protamine is a drug that reverses the anticoagulant effects of heparin by binding to it. ...

Mechanism of anticoagulant action

Heparin binds to the enzyme inhibitor antithrombin III (AT-III) causing a conformational change which results in its active site being exposed. The activated AT-III then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa. The rate of inactivation of these proteases by AT-III increases 1000-fold due to the binding of heparin.^[9] Antithrombin is a small molecule that inactivates several enzymes of the coagulation system. ... Factor X, also known by the eponym Stuart-Prower factor or as thrombokinase, is an enzyme (EC 3. ...

AT-III binds to a specific pentasaccharide sulfation sequence contained within the heparin polymer

The conformational change in AT-III on heparin binding mediates its inhibition of factor Xa. For thrombin inhibition however, thrombin must also bind to the heparin polymer at a site proximal to the pentasaccharide. The highly negative charge density of heparin contributes to its very strong electrostatic interaction with thrombin.^[1] The formation of a ternary complex between AT-III, thrombin and heparin results in the inactivation of thrombin. For this reason heparin's activity against thrombin is size dependent, the ternary complex requiring at least 18 saccharide units for efficient formation.^[10] In contrast anti factor Xa activity only requires the pentasaccharide binding site. Electrostatics is the branch of physics that deals with the force exerted by a static (i. ... Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... A ternary complex is a polymer formed by electrostatic interaction between oppositely charged polyelectrolytes[1]. ...

This size difference has led to the development of low molecular weight heparins (LMWHs) and more recently to fondaparinux as pharmaceutical anticoagulants. Low molecular weight heparins and fondaparinux target anti factor Xa activity rather than anti thrombin (IIa) activity, with the aim of facilitating a more subtle regulation of coagulation and an improved therapeutic index. The chemical structure of fondaparinux is shown to the left. This is a synthetic pentasaccharide whose chemical structure is almost identical to the structure the AT-III binding pentasaccharide sequence that can be found within polymeric heparin and heparan sulfate. Image File history File links Download high-resolution version (897x262, 43 KB) I, the creator of this work, hereby release it into the public domain. ... Image File history File links Download high-resolution version (897x262, 43 KB) I, the creator of this work, hereby release it into the public domain. ... Fondaparinux (Arixtra) is an anticoagulant medication. ... In medicine, low molecular weight heparin (LMWH) is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis. ... Fondaparinux (Arixtra) is an anticoagulant medication. ... Heparan Sulfate (HS) is a linear polysaccharide found in all animal tissues. ...

With LMWH and fondaparinux, there is a reduced risk of osteoporosis and heparin-induced thrombocytopenia (HIT). Monitoring of the APTT is also not required and indeed does not reflect the anticoagulant effect, as APTT is insensitive to alterations in factor Xa. Osteoporosis is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. ... Heparin-induced thrombocytopenia (HIT) with or without thrombosis (HITT) is thrombocytopenia (low platelet counts) due to the administration of heparin. ... The partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) is a commonly performed test for the system of coagulation, especially its intrinsic pathway. ...

Danaparoid, a mixture of heparan sulfate, dermatan sulfate and chondroitin sulfate can be used as an anticoagulant in patients who have developed HIT. Because danaparoid does not contain heparin or heparin fragments cross-reactivity of danaparoid with heparin-induced antibodies is reported as less than 10%.^[11] Danaparoid sodium (OrgaranÂ®) is an anticoagulant that works by inhibiting thrombin. ... Heparan Sulfate (HS) is a linear polysaccharide found in all animal tissues. ... Dermatan sulfate is a glycosaminoglycan, formerly called a mucopolysaccharide, found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs. ... Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) found in connective tissue and the nervous system, normally attached to a protein core. ...

The effects of heparin are measured in the lab by the partial thromboplastin time (aPTT), (the time it takes the blood plasma to clot). The partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) is a commonly performed test for the system of coagulation, especially its intrinsic pathway. ... Blood plasma is the liquid component of blood, in which the blood cells are suspended. ...

Heparin's exact physiological role is still unclear, because blood anti-coagulation is mostly achieved by endothelial cell-derived heparan sulfate proteoglycans.^[12] Heparin is usually stored within the secretory granules of mast cells and only released into the vasculature at sites of tissue injury. It has been proposed that rather than anticoagulation the main purpose of heparin is in a defensive mechanism at sites of tissue injury against invading bacteria and other foreign materials.^[13] Heparan Sulfate (HS) is a linear polysaccharide found in all animal tissues. ... Mast cells A mast cell (or mastocyte) is a resident cell of areolar connective tissue (loose connective tissue) that contains many granules rich in histamine and heparin. ... Human circulatory system. ...

History

Heparin is one of the oldest drugs currently still in widespread clinical use. Its discovery in 1916 predates the establishment of the United States Food and Drug Administration, although it did not enter clinical trials until 1935.^[14] It was originally isolated from canine liver cells, hence its name (hepar or "ηπαρ" is Greek for "liver"). Heparin's discovery can be attributed to the research activities of two men, Jay McLean and William Henry Howell. â€œFDAâ€ redirects here. ... For the bird, see Liver bird. ... William Henry Howell, Ph. ...

In 1916 McLean, a second-year medical student at Johns Hopkins University, was working under the guidance of Howell investigating pro-coagulant preparations, when he isolated a fat soluble phosphatide anti-coagulant. It was Howell who coined the term heparin for this type of fat soluble anticoagulant in 1918. In the early 1920s, Howell isolated a water soluble polysaccharide anticoagulant which was also termed heparin, although it was distinct from the phosphatide preparations previously isolated. It is probable that the work of McLean changed the focus of the Howell group to look for anticoagulants, which eventually led to the polysaccharide discovery. The Johns Hopkins University, founded in 1876, is a private institution of higher learning located in Baltimore, Maryland, United States. ...

Between 1933 and 1936, Connaught Medical Research Laboratories, then a part of the University of Toronto, perfected a technique for producing safe non-toxic heparin that could be administered to patients in a salt solution. The first human trials of heparin began in May 1935 and by 1937 it was clear that Connaught's heparin was a safe, easily available and effective blood anticoagulant. Prior to 1933, heparin was available, but in small amounts, was extremely expensive, toxic and consequently of no medical value.^[15] The University of Toronto (U of T) is a public research university in the city of Toronto, Ontario, Canada. ...

For a full discussion of the events surrounding heparin's discovery see Marcum J. (2000).^[16]

Novel drug development opportunities for heparin

As detailed in the table below, there is a great deal of potential for the development of heparin like structures as drugs to treat a wide range of diseases in addition to their current use as anticoagulants.^[17]^[18] For other meanings, see Drug (disambiguation). ... This article is about the medical term. ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ...

- indicates no information available In health care, including medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a process in which a medicine or other medical treatment is tested for its safety and effectiveness, often in comparison to existing treatments. ... Encephalomyelitis is a general term for inflammation of the brain and spinal cord, describing a number of disorders: acute disseminated encephalomyelitis or postinfectious encephalomyelitis, a demyelinating disease of the brain and spinal cord, possibly triggered by vaccination or viral infection; encephalomyelitis disseminata, a synonym for multiple sclerosis; equine encephalomyelitis, a... Animal model refers to a non-human animal with a disease that is similar to a human condition. ... For the play, see Hay Fever. ... Arthritis (from Greek arthro-, joint + -itis, inflammation; plural: arthritides) is a group of conditions where there is damage caused to the joints of the body. ... Tropocollagen triple helix. ... Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ... Anecdotal evidence is an informal account of evidence in the form of an anecdote or hearsay. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... Tumor (American English) or tumour (British English) originally means swelling, and is sometimes still used with that meaning. ... For the musical composition, see Metastasis (Xenakis composition). ... Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. ... In medicine, inflammatory bowel disease (IBD) is a group of inflammatory conditions of the large intestine and, in some cases, the small intestine. ... Interstitial cystitis (commonly abbreviated to IC) is a urinary bladder disease of unknown cause characterised by urinary frequency (as often as every 10 minutes), urgency, pressure and/or pain in the bladder and/or pelvis. ... Transplant rejection occurs when the immune system of the recipient of a transplant attacks the transplanted organ or tissue. ... Allography, from the Greek for other writing, has several meanings which all relate to how words and sounds are written down. ...

As a result of heparins effect on such a wide variety of disease states a number of drugs are indeed in development whose molecular structures are identical or similar to those found within parts of the polymeric heparin chain.^[17]

Pentosan Polysulfate Pentosan polysulfate (sold under the name Elmiron) was the first --and only-- oral medication approved by the US FDA for the treatment of interstitial cystitis, also known as painful bladder syndrome. ... Look up inhibition, inhibitor in Wiktionary, the free dictionary. ...

Evolutionary conservation of heparin

In addition to the bovine and porcine tissue from which pharmaceutical grade heparin is commonly extracted, heparin has also been extracted and characterised from the following species:

The biological activity of heparin within species 6-11 is unclear and further supports the idea that the main physiological role of heparin is not anticoagulation. These species do not possess any blood coagulation system similar to that present within the species listed 1-5. The above list also demonstrates how heparin has been highly evolutionarily conserved with molecules of a similar structure being produced by a broad range of organisms belonging to many different phyla. This article is about the animal. ... This article or section may be confusing for some readers, and should be edited to be clearer or more simplified. ... This article is about the animal. ... Human beings are defined variously in biological, spiritual, and cultural terms, or in combinations thereof. ... Subfamilies and Genera Neophoberinae Acanthacaris Thymopinae Nephropsis Nephropides Thymops Thymopsis Nephropinae Homarus Nephrops Homarinus Metanephrops Eunephrops Thymopides Clawed lobsters comprise a family (Nephropidae, sometimes also Homaridae) of large marine crustaceans. ... Subclasses Pteriomorpha (marine mussels) Palaeoheterodonta (freshwater mussels) Heterodonta (zebra mussels) The term mussel is used for several families of bivalve molluscs inhabiting lakes, rivers, and creeks, as well as intertidal areas along coastlines worldwide. ... For other uses, see Clam (disambiguation). ... Superfamilies Alpheoidea Atyoidea Bresilioidea Campylonotoidea Crangonoidea Galatheacaridoidea Nematocarcinoidea Oplophoroidea Palaemonoidea Pandaloidea Pasiphaeoidea Procaridoidea Processoidea Psalidopodoidea Stylodactyloidea True shrimp are swimming, decapod crustaceans classified in the infraorder Caridea, found widely around the world in both fresh and salt water. ... Mangrove crabs are crabs that live among mangroves, and may belong to many different species and even families. ... Suborders Laganina Rotulina Scutellina Sand dollars are in the Echinoid (Echinoderms) class of marine animals. ... This page is a candidate to be copied to Wiktionary. ... In biological taxonomy, a phylum (Greek plural: phyla) is a taxon in the rank below kingdom and above class. ...

Other uses/information

This article or section does not cite any references or sources. ... A mast cell (or mastocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. ... Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ... Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... A range of Vacutainer tubes containing blood. ... Blood flows from digestive system heart to arteries, which narrow into arterioles, and then narrow further still into capillaries. ... This article is about the chemical element named Lithium. ... EDTA is a widely-used acronym for the chemical compound ethylenediamine tetraacetic acid (and many other names, see table). ... This article is about the electrically charged particle. ... An immunoassay is a biochemical test that measures the concentration of a substance in a biological liquid, typically serum or urine, using the reaction of an antibody or antibodies to its antigen. ... For sodium in the diet, see Edible salt. ... For most cardiothoracic operations such as coronary artery bypass grafting, the cardiopulmonary bypass is performed using a heart-lung machine (or cardiopulmonary bypass machine). ... This article does not cite any references or sources. ... Wikipedia does not yet have an article with this exact name. ... In chemistry, a ligand is an atom, ion, or molecule (see also: functional group) that generally donates one or more of its electrons through a coordinate covalent bond to, or shares its electrons through a covalent bond with, one or more central atoms or ions (these ligands act as a... Protein purification is the process of isolating proteins from a homogenate, which may comprise cell and tissue components, including DNA, cell membrane and other proteins. ... This article is about the clotting of blood. ... Fibrin is a protein involved in the clotting of blood. ... Peritoneal dialysis In medicine, peritoneal dialysis is a method for removing waste such as urea and potassium from the blood, as well as excess fluid, when the kidneys are incapable of this (i. ...

Popular culture

This article is about the author. ... Wikibooks has a book on the topic of Angels and Demons Angels and Demons (Angels & Demons) is a bestselling mystery novel by Dan Brown. ... For other uses, see Death (disambiguation). ... For other uses, see Stroke (disambiguation). ... This article is about the US sitcom. ...

References

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^ Linhardt RJ, Gunay NS. (1999). "Production and Chemical Processing of Low Molecular Weight Heparins". Sem. Thromb. Hem. 3: 5-16. PMID 10549711.
^ Gatti, G., Casu, B. et al (1979). "Studies on the Conformation of Heparin by ^lH and ¹³C NMR Spectroscopy". Macromolecules 12 (5): 1001-1007.
^ Ferro D, Provasoli A, et al (1990). "Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences". Carbohydr. Res. 195: 157-167. PMID 2331699.
^ Mulloy B, Forster MJ, Jones C, Davies DB. (1993). "NMR and molecular-modelling studies of the solution conformation of heparin". Biochem. J. 293: 849-858. PMID 8352752.
^ Guyton, A. C.; Hall, J. E. (2006). Textbook of Medical Physiology. Elsevier Saunders, 464. ISBN 0-7216-0240-1.
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^ Kusmer, Ken. "3rd Ind. preemie infant dies of overdose", Fox News (Associated Press), 2006-09-20. Retrieved on 2007-01-08.
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^ Petitou M, Herault JP, Bernat A, Driguez PA, et al. (1999). "Synthesis of Thrombin inhibiting Heparin mimetics without side effects". Nature 398: 417-422. PMID 10201371.
^ Shalansky, Karen. DANAPAROID (Orgaran®) for Heparin-Induced Thrombocytopenia. Vancouver Hospital & Health Sciences Centre, February 1998 Drug & Therapeutics Newsletter. Retrieved on 2007-01-08.
^ Kojima T, Leone CW, et al (1992). "Isolation and characterisation of heparan sulfate proteoglycans produced by cloned rat microvascular endothelial cells". J. Biol. Chem. 267: 4859-4569. PMID 1537864.
^ Nader, HB et al (1999). "Heparan sulfates and heparins: similar compounds performing the same functions in vertebrates and invertebrates?". Braz. J. Med. Biol. Res. 32 (5): 529-538. PMID 10412563.
^ Linhardt RJ. (1991). "Heparin: An important drug enters its seventh decade". Chem. Indust. 2: 45-50.
^ [Christopher J.]. [http://www.healthheritageresearch.com/Heparin-Conntact9608.html Miracle Blood Lubricant: Connaught and the Story of Heparin, 1928-1937]. Health Heritage Research Services. Retrieved on 2007-05-21.
^ Marcum J. (2000). "The origin of the dispute over the discovery of heparin". J. Hist. Med. Allied. Sci. 55: 37-66. PMID 10734720.
^ ^a ^b Lever R. and Page C.P. (2002). "Novel drug opportunities for heparin". Nat. Rev. Drug Discov. 1 (2): 140-148. PMID 12120095.
^ Coombe D.R and Kett W.C. (2005). "Heparan sulfate-protein interactions: therapeutic potential through structure-function insights". Cell. Mol. Life Sci. 62 (4): 410-424. PMID 15719168.
^ Warda M, Mao W. et al (2003). "Turkey intestine as a commercial source of heparin? Comparative structural studies of intestinal avian and mammalian glycosaminoglycans.". Comp. Biochem. Physiol. B Biochem. Mol. Biol. 134 (1): 189-197. PMID 12524047.
^ Ototani N, Kikuchi M, Yosizawa Z. (1981). "Comparative studies on the structures of highly active and relatively inactive forms of whale heparin". J Biochem (Tokyo) 90 (1): 241-246. PMID 7287679.
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