An acidic glycosaminoglycan found especially in lung and liver tissue and having the ability to prevent the clotting of blood, used in the treatment of thrombosis.
[Late Latin hēpar, liver (from Greek) + –IN.]
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Results for heparin
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Oncology Encyclopedia:
Heparin
Key Terms: Angiogenesis, Anticoagulant, Blood clot, Coagulation, Embolism, Endothelial cells, Parenteral, Procoagulants, Thromboembolism.
Definition
Heparin is a drug that helps prevent blood clots from forming and belongs to the family of drugs called anticoagulants (blood thinners), although it does not actually thin the blood. It is sold in the United States under the brand names of Calciparine, Liquaemin, Calciparine, Hepalean, and Heparin Leo, and Calcilean in Canada.
Purpose
Heparin is used to decrease the clotting ability of the blood and to help prevent harmful clots from forming in the blood vessels. Heparin will not dissolve blood clots that have already formed, but it may prevent the clots from becoming larger and causing more serious problems. Heparin possesses several antithrombotic mechanisms. It is often used as a treatment for certain blood vessel, heart, and lung conditions and is also used to prevent blood clotting during open-heart surgery, bypass surgery, and dialysis. Heparin is used in low doses to prevent the formation of blood clots in certain patients, especially those who must have certain types of surgery or who must remain in bed for a long time. It is also used for the long-term treatment of thromboembolic disease, a common side effect of cancer.
One of the most common hematological complications is disordered coagulation. Approximately 15% of all cancer patients are affected by thromboembolic disease, which is the second leading cause of death for cancer patients. However, thromboembolic disease may represent only one of many complications in end-stage patients. Thromboembolic disease includes superficial and deep venous thrombosis, pulmonary emboli, thrombosis of venous access devices, arterial thrombosis, and embolism. The cancer itself or cancer treatments may induce coagulation. For example, chemotherapy can increase the risk of thromboembolic disease. An increased risk for arterial thrombosis has been observed with chemotherapy treatment.
Cancer and its treatment can affect all three causes of thromboembolic disease, including the alteration of blood flow, damage to endothelial cells (the cells in blood vessels), and enhancing procoagulants (causing the blood to clot). Cancer can affect blood flow by mechanically affecting blood vessels close to a tumor. In addition, tumors cause angiogenesis, which may create complexes of blood vessels that have a disordered appearance and flow (varying in magnitude and direction). Chemotherapy or tumors may directly damage endothelial cells. Procoagulants may be secreted into the blood stream by cancer cells or can be increased on the surface of cancer cells.
Antithrombotic treatment, in the form of the low-molecular-weight heparin reviparin, has been shown for the first time to safely improve the outcomes of patients with an acute myocardial infarction. The new findings show that reviparin "clearly improves the outcomes of patients who undergo thrombolysis with streptokinase or urokinase, and it also appears to be a useful adjunct for patients treated with primary percutaneous coronary intervention [PCI]," said Dr. Anderson, associate chief of the division of cardiology at LDS Hospital in Salt Lake City. The study has some limitations.
Description
Heparin is the most common anticoagulant used and the generic name product may be available in the U.S. and Canada.
Mechanisms of Action:
Heparin increases the release of specific proteins, like tissue plasminogen activator and tissue factor pathway inhibitor (TFPI), into the blood in order to inhibit blood coagulation. It can also increase the activity of these proteins. Heparin augments the activity of antithrombin III, a natural compound that inhibits activated clotting factors from contributing to more coagulation. Furthermore, heparin has been found to inhibit substances that may contribute to angiogenesis, including vascular endothelial growth factor, tissue factor, and plateletactivating factor.
Whether anticoagulants like heparin may also improve cancer survival rates independent of their effect on thromboembolism has been investigated. In fact, experimental and clinical data have demonstrated that heparin is an effective compound in preventing metastases. Many investigators have shown that heparin inhibits tumor metastasis in experimental animals; a few clinical trials also suggest a positive effect in humans with cancer.
Recommended Dosage
Heparin is available only with a doctor's prescription, in parenteral and injection (United States and Canada) dosage forms. A doctor will need to prescribe a specific dose for an individual's based on the type of heparin, as well as the patient's medical condition and body weight.
Dosing Schedule
Heparin should be taken under the doctor's direction and at the same time every day. If a dose is missed, take it as soon as possible. However, if a dose is missed until the following day, patients should not double-dose, but just take the usual daily dose. Double-dosing may cause bleeding.
Precautions
Some medications should not be combined. Over-the-counter medicines, vitamins, and herbal products may cause interactions when combined with heparin, so the patient should check with the doctor monitoring the heparin medication before taking any new medication, even when prescribed by another doctor.
Patients who are pregnant, breastfeeding, have given birth recently, or using an IUD for birth control should consult their doctors. The doctor should also be notified if radiation treatments, surgery, or a fall or other injury has recently occurred.
The presence of other medical problems may affect the use of heparin. Patients should be sure to tell their doctors about any other medical problems, in particular:
- allergies or asthma (or history of)
- blood disease or bleeding problems
- colitis or stomach ulcer (or history of)
- diabetes mellitus
- high blood pressure (hypertension)
- kidney disease
- liver disease
- tuberculosis (active)
Side Effects
The doctor should be contacted immediately if any of these side effects are present:
- wheezing or trouble breathing
- skin rash, itching, or hives
- red or "coffee ground" vomit
- unexplained nosebleeds
- swelling in the face, lips, or tongue
- blood in urine or stools
- black tarry stools
Interactions
Using any of the following medicines together with heparin may increase the risk of bleeding. Again, candidates for heparin should alert their physicians if they are taking any of these medications:
- aspirin
- persantine
- carbenicillin by injection (Geopen)
- cefamandole (Mandol)
- cefoperazone (Cefobid)
- cefotetan (Cefotan)
- dipyridamole (Persantine)
- divalproex (Depakote)
- medicine for inflammation or pain (Motrin, Aleve), except narcotics
- medicine for overactive thyroid
- pentoxifylline (Trental)
- plicamycin (Mithracin)
- probenecid (Benemid)
- sulfinpyrazone (Anturane)
- ticarcillin (Ticar)
- valproic acid (Depakene)
- medicines via intramuscular injection
—Crystal Heather Kaczkowski, MSc.
Sci-Tech Encyclopedia:
Heparin
A highly sulfated mucopolysaccharide with blood anticoagulant activity, isolated from mammalian (chiefly beef) tissues. Heparin was first found in abundance in the liver, hence the name, but it is present in substantial amounts in the spleen, muscle, and lung as well. In the blood of most mammals, heparin is an antagonist to thrombin, prothrombin, and thromboplastin. It lessens the tendency of platelets to agglutinate. It is used in the treatment of venous thrombosis, embolism, myocardial infarction, and certain types of cerebral thrombosis. See also Polysaccharide.
World of the Body:
heparin
This, the body's natural anticoagulant, is a muco-polysaccharide of variable molecular weight (12 000-25 000) containing sulphate groups. Heparin is produced in the liver and stored there and in other cells, such as mast cells. The levels in circulating blood are very low in normal conditions. It is able to prevent blood coagulation by acting at three separate points on the ‘cascade’ of chemical events in the plasma that causes blood clotting. First it prevents the interaction of thrombin with fibrinogen, so that the conversion of the latter to fibrin, the basic structural element of a clot, is prevented. Second, it prevents the conversion of prothrombin to thrombin and causes the destruction of Factor Xa, an early factor in the cascade. Given intravenously or subcutaneously heparin can be used to treat deep vein thrombosis and acute arterial thrombosis.
— Alan W. Cuthbert
See also blood; blood clotting.
Drug Info:
Heparin
Brand names: Hemochron™, Hep-Lock®, Hep-Lock® U/P, Heparin, HepFlush®-10, Momoject®, Monoject®
Chemical formula:
- Español:
- Inyección de heparina
Heparin injection
What is heparin injection?
Heparin is an anticoagulant, sometimes called a blood thinner. However, heparin does not thin the blood or dissolve clots that have already formed. Instead, heparin prevents clot formation and stops clots from getting bigger. Heparin helps to treat or prevent clots in the veins, arteries, lungs, or the heart, and to prevent clotting during open-heart surgery, dialysis, or in very sick patients who stay in bed. Generic heparin injections are available.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:
• aneurysm
• bleeding disorders, such as hemophilia
• bowel disease, or diverticulitis
• endocarditis
• liver disease
• recent surgery or delivery of a baby
• stomach ulcers
• an unusual or allergic reaction to heparin, benzyl alcohol, sulfites, other medicines, foods, dyes, or preservatives
How should I use this medicine?
Heparin is given by injection or infusion into a vein by a health-care professional in a hospital. Heparin also can be given by injection of small amounts under the skin in the hospital, clinic, or home-care setting. If you are to give yourself injections, make sure you understand how to fill the syringe and give the injection, and how to dispose of used syringes and needles. Use disposable syringes only once, and throw away syringes and needles in a closed container. Use exactly as directed. Do not exceed the prescribed dose, and try not to miss doses.
What if I miss a dose?
Use missed doses as soon as you remember, unless it is nearly time for your next dose; then, skip the missed dose and resume your regular schedule with the next dose. Do not double doses.What drug(s) may interact with heparin?
• other drugs that treat or prevent blood clots
• antiinflammatory drugs, such as ibuprofen (Motrin®) or naproxen (Aleve®)
• aspirin
• diflunisal
• fish oil (omega-3 fatty acids) supplements
• herbal products, such as those that contain garlic, ginger, ginkgo, horse chestnut, or feverfew
Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.
What should I watch for while taking heparin?
Patients recently receiving heparin should carry an identification card containing their name, name and dose of medicine(s) being used, and name and phone number of their prescriber or health care professional or person to contact in an emergency. Notify your prescriber or health care professional at once if you have cold, blue hands or feet, or any unusual bleeding. Monitor your skin closely for easy bruising or red spots, which can indicate bleeding.
If you are going to have surgery or dental work, tell your prescriber or health care professional that you have received heparin. Be careful brushing and flossing your teeth or using a toothpick while receiving heparin because you may bleed more easily.
Be careful to avoid injury while you are using heparin. Report any injuries to your prescriber or health care professional.
What side effects might I notice from receiving heparin?
Side effects that you should report to your prescriber or health care professional as soon as possible:
• any sign of bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine, bleeding gums, nosebleeds
• back or stomach pain
• bleeding in the eye
• cold, blue, or painful hands and feet
• coughing up blood
• difficulty breathing, fever, chills, or hives
• heavy menstrual bleeding
• skin rash or peeling
Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• burning or itching on the bottoms of the feet
• irritation at the injection site
Where can I keep my medicine?
Keep out of the reach of children.
Store unopened vials at room temperature between 15—25 degrees C (59—77 degrees F); do not freeze. Do not use if solution is discolored or particulate matter is present. Throw away any unused medicine after the expiration date.
Store needles and syringes out of the reach of children. Make sure you receive a puncture-resistant container to dispose of the needles and syringes once you have finished with them. Do not reuse these items. Return the container to your prescriber or health care professional for proper disposal.
Last updated: 7/1/2002
Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.
Britannica Concise Encyclopedia:
heparin
For more information on heparin, visit Britannica.com.
Sports Science and Medicine:
heparin
A complex organic acid found in mast cells (large cells in the connective tissue involved in inflammation response). It inhibits blood coagulation by interfering with the formation and action of thrombin (a blood clotting factor). A heparin drug can be prepared from snake venom. In addition to its anticoagulant properties, it has effects similar to caffeine, increasing free fatty acid levels. These effects may be utilized during aerobic exercise, reducing the rate of muscle glycogen utilization and delaying fatigue.
Columbia Encyclopedia:
heparin
(hĕp'ərĭn) , anticoagulant produced by cells in many animals. A polysaccharide, heparin is found in the human body and occurs in greatest concentration in the tissues surrounding the capillaries of the lungs and the liver. The substance, extracted from animal tissues, is used clinically to delay blood clotting.
Veterinary Dictionary:
heparin
An acid mucopolysaccharide present in many tissues, especially the liver and lungs, and having potent anticoagulant properties. It also has lipotrophic properties, promoting transfer of fat from blood to the fat depots by activation of lipoprotein lipase. Also, a mixture of active principles capable of prolonging blood clotting time, obtained from domestic animals; used in the prophylaxis and treatment of disorders in which there is excessive or undesirable clotting and as a preservative for blood specimens.
Wikipedia:
heparin
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Heparin
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| Systematic (IUPAC) name | |
| see Heparin structure | |
| Identifiers | |
| CAS number | |
| ATC code | B01 C05BA03 S01XA14 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C12H19NO20S3 |
| Mol. mass | 12000-15000 g/mol |
| Pharmacokinetic data | |
| Bioavailability | nil |
| Metabolism | hepatic |
| Half life | 1.5 hrs |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
C |
| Legal status |
? |
| Routes | i.v., s.c. |
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]
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.
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.
 GlcA-GlcNAc
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 GlcA-GlcNS
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 IdoA-GlcNS
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 IdoA(2S)-GlcNS
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 IdoA-GlcNS(6S)
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 IdoA(2S)-GlcNS(6S)
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Abbreviations
- GlcA = β-L-glucuronic acid
- IdoA = α-L-iduronic acid
- IdoA(2S) = 2-O-sulfo-α-L-iduronic acid
- GlcNAc = 2-deoxy-2-acetamido-α-D-glucopyranosyl
- GlcNS = 2-deoxy-2-sulfamido-α-D-glucopyranosyl
- GlcNS(6S) = 2-deoxy-2-sulfamido-α-D-glucopyranosyl-6-O-sulfate
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.[1] 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.[2] 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.
In the image above:
- A = 1HPN (all IdoA(2S) residues in 2S0 conformation) Jmol viewer
- B = van der Waals radius space filling model of A
- C = 1HPN (all IdoA(2S) residues in 1C4 conformation) Jmol viewer
- D = van der Waals radius space filling model of C
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.
Medical use
Heparin is a naturally occurring anticoagulant produced by basophils and
- Acute coronary syndrome, e.g., myocardial infarction
- Atrial fibrillation
- Deep-vein thrombosis and pulmonary embolism
- Cardiopulmonary bypass for heart surgery.
Administration
Details of administration are available in clinical practice guidelines by the American College of Chest Physicians[4]:
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.
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.
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.
Rarer side effects include alopecia and osteoporosis with chronic use.
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.[5]
Treatment of overdose
In case of overdose, protamine sulfate can be given to counteract the action of heparin, in the same amount as heparin.
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.[6]
AT-III binds to a specific pentasaccharide sulfation sequence contained within the heparin polymer
GlcNAc/NS(6S)-GlcA-GlcNS(3S,6S)-IdoA(2S)-GlcNS(6S)
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.[7] 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.[8] In contrast anti factor Xa activity only requires the pentasaccharide binding site.
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.
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.
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%.[9]
The effects of heparin are measured in the lab by the partial thromboplastin time (aPTT), (the time it takes the
Heparin's exact physiological role is still unclear, because blood anti-coagulation is mostly achieved by endothelial
cell-derived heparan sulfate proteoglycans.[10] Heparin is usually stored within the secretory granules of
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.[12] 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.
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.
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.[13]
For a full discussion of the events surrounding heparin's discovery see Marcum J. (2000).[14]
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.[15][16]
| Disease states sensitive to heparin | Heparins effect in experimental models | Clinical status |
| Adult respiratory distress syndrome | Reduces cell activation and accumulation in airways, neutralizes mediators and cytotoxic cell products, and improves lung function in animal models | Controlled clinical trials |
| Allergic encephalomyelitis | Effective in animal models | - |
| Allergic rhinitis | Effects as for adult respiratory distress syndrome, although no specific nasal model has been tested | Controlled clinical trial |
| Arthritis | Inhibits cell accumulation, collagen destruction and angiogenesis | Anecdotal report |
| Asthma | As for adult respiratory distress syndrome, however it has also been shown to improve lung function in experimental models | Controlled clinical trials |
| Cancer | Inhibits tumour growth, metastasis and angiogenesis, and increases survival time in animal models | Several anecdotal reports |
| Delayed type hypersensitivity reactions | Effective in animal models | - |
| Inflammatory bowel disease | Inhibits inflammatory cell transport in general. No specific model tested | Controlled clinical trials |
| Interstitial cystitis | Effective in a human experimental model of interstitial cystitis | Related molecule now used clinically |
| Transplant rejection | Prolongs allograph survival in animal models | - |
- indicates no information available
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.[15]
| Drug molecule | Effect of new drug compared to heparin | Biological activities |
| Heparin tetrasaccharide | Non-anticoagulant, non-immunogenic, orally active | Anti-allergic |
| Pentosan polysulfate | Plant derived, little anticoagulant activity, Anti-inflammatory, orally active | Anti-inflammatory, anti-adhesive, anti-metastatic |
| Phosphomannopentanose sulfate | Potent inhibitor of heparanase activity | Anti-metastatic, anti-angiogenic, anti-inflammatory |
| Selectively chemically O-desulphated heparin | Lacks anticoagulant activity | Anti-inflammatory, anti-allergic, anti-adhesive |
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:
- Turkey.[17]
- Whale.[18]
- Dromedary camel.[19]
- Mouse.[20]
- Humans.[21]
- Lobster.[22]
- Fresh water mussel.[23]
- Clam.[24]
- Shrimp.[25]
- Mangrove crab.[26]
- Sand dollar.[26]
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.
Other uses/information
- Heparin gel (topical) may sometimes be used to treat sports injuries. It is known that the diprotonated form of
histamine binds site specifically to heparin.[27] The release of histamine from
mast cells at a site of tissue injury contributes to an inflammatory response. The rationale behind the use of such topical gels may be to block the activity of released histamine and so help to reduce inflammation. - Heparin gains the capacity to initiate angiogenesis when its copper salt is formed. Copper free molecules are non-angiogenic.[28][29] In contrast heparin may inhibit angiogenesis when it is administered in the presence of corticosteroids.[30] This anti-angiogenic effect is independent of heparins anticoagulant activity.[31]
- Test tubes, Vacutainers, and capillary tubes that use the lithium salt of heparin (lithium heparin) as an anticoagulant are usually marked with green stickers and green tops. Heparin has the advantage over EDTA as an anticoagulant, as it does not affect levels of ions (such as calcium). Heparin can interfere with some immunoassays, however. As lithium heparin is usually used, a person's lithium levels cannot be obtained from these tubes; for this purpose, royal-blue topped Vacutainers containing sodium heparin are used.
- Heparin-coated blood oxygenators are available for use in heart-lung machines. Among other things, these specialized oxygenators are thought to improve overall biocompatibility and host homeostasis by providing characteristics similar to native endothelium.
- The DNA binding sites on RNA polymerase can be occupied by heparin, preventing the polymerase binding to promoter DNA. This property is exploited in a range of molecular biological assays.
- Common diagnostic procedures require PCR amplification of a patient's DNA, which is easily extracted from white blood cells treated with heparin. This poses a potential problem, since heparin may be extracted along with the DNA, and it has been found to interfere with the PCR reaction at levels as low as 0.002 U in a 50 μL reaction mixture.[32]
- Immobilized heparin can be used as an affinity ligand in protein purification. In this capacity it can be used in two ways. The first of which is to use
heparin to select out specific
coagulation factors or other types of heparin binding proteins from a complex mixture of non-heparin binding proteins. Specific proteins can then be selectively dissociated from heparin with the use of differing salt concentrations or by use of a salt gradient. The second use is to use heparin as a high capacity cation exchanger. This use takes advantage of heparins high number of anionic sulfate groups. These groups will capture common cations such as Na+ or Ca2+ in solution.
- Heparin is also used to break up fibrin in peritoneal dialysis effluent.
Popular culture
- Heparin was featured in Dan Brown's novel Angels and Demons, where the intentional overdose of the drug was used in the murder of a significant character that was disguised to resemble a death by stroke.
- Was featured in the television show Scrubs. The protagonist (JD) was called in by a new medical student on whether low-molecular weight or fractionated heparin should be used for a patient. However both are the same.
References
- ^ 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.
- ^ Hirsh J, Raschke R (2004). "Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy". Chest 126 (3 Suppl): 188S-203S. DOI:10.1378/chest.126.3_suppl.188S. PMID 15383472.
- ^ Kusmer, Ken. "3rd Ind. preemie infant dies of overdose", Fox News (Associated Press), 2006-09-20. Retrieved on 2007-01-08.
- ^ Bjork I, Lindahl U. (1982). "Mechanism of the anticoagulant action of heparin". Mol. Cell. Biochem. 48: 161-182.
- ^
- ^ 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.
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External links
| Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01) | |
|---|---|
| Vitamin K antagonists | Acenocoumarol • Clorindione • Coumatetralyl • Dicumarol (Dicoumarol) • Diphenadione • Ethyl biscoumacetate • Phenprocoumon • Phenindione • Tioclomarol • Warfarin |
| Heparin group | Antithrombin III • Danaparoid • Heparin • Sulodexide • low molecular weight heparin (Bemiparin, Dalteparin, Enoxaparin, Nadroparin, Parnaparin, Reviparin, Tinzaparin) |
| Glycoprotein IIb/IIIa inhibitors | Abciximab • Eptifibatide • Tirofiban |
| Other platelet aggregation inhibitors |
Acetylsalicylic acid/Aspirin • |