Dextran
Encyclopedia
Dextran is a complex, branched glucan
(polysaccharide
made of many glucose
molecules) composed of chains of varying lengths (from 3 to 2000 kilodaltons
). It is used medicinally as an antithrombotic
(anti-platelet
), to reduce blood viscosity
, and as a volume expander in anemia
.
The straight chain consists of α-1,6 glycosidic linkages between glucose molecules, while branches begin from α-1,3 linkages. (For information on the numbering of carbon
atom
s in glucose, see the glucose
article.) Dextran is synthesized from sucrose by certain lactic-acid bacteria, the best-known being Leuconostoc mesenteroides
and Streptococcus mutans
. Dental plaque
is rich in dextrans. Dextran is also formed by the lactic acid bacterium Lactobacillus brevis
to create the crystals of tibicos
, or water kefir fermented beverage which supposedly has some health benefits.
Dextran was first discovered by Louis Pasteur
as a microbial product in wine.
. The antithrombotic effect of dextran is mediated through its binding of erythrocytes, platelets, and vascular endothelium
, increasing their electronegativity
and thus reducing erythrocyte aggregation and platelet
adhesiveness. Dextrans also reduce factor VIII-Ag Von Willebrand factor
, thereby decreasing platelet function. Clots formed after administration of dextrans are more easily lysed due to an altered thrombus structure (more evenly distributed platelets with coarser fibrin
). By inhibiting α-2 antiplasmin, dextran serves as a plasminogen activator and therefore possesses thrombolytic features.
Outside from these features, larger dextrans, which do not pass out of the vessels, are potent osmotic agents, and thus have been used urgently to treat hypovolemia
. The hemodilution caused by volume expansion with dextran use improves blood flow, thus further improving patency of microanastomoses and reducing thrombosis. Still, no difference has been detected in antithrombotic effectiveness in comparison of intraarterial and intravenous administration of dextran.
Dextrans are available in multiple molecular weights ranging from 10,000 Da to 150,000 Da. The larger dextrans are excreted poorly from the kidney and therefore remain in the blood for as long as weeks until they are metabolized. Subsequently, they have prolonged antithrombotic and colloidal effects. In this family, dextran-40 (MW: 40,000 Da), has been the most popular member for anticoagulation
therapy. Close to 70% of dextran-40 is excreted in urine within the first 24 hours after intravenous infusion while the remaining 30% will be retained for several more days.
, volume overload, pulmonary edema
, cerebral edema
, or platelet dysfunction. An uncommon but significant complication of dextran osmotic effect is acute renal failure
. The pathogenesis of this renal failure is the subject of many debates with direct toxic effect on tubules and glomerulus
versus intraluminal hyperviscosity being some of the proposed mechanisms. Patients with history of diabetes mellitus
, renal insufficiency
, or vascular disorders are most at risk. Brooks and others recommend the avoidance of dextran therapy in patients with chronic renal insufficiency and CrCl<40 cc per minute.
Glucan
A glucan molecule is a polysaccharide of D-glucose monomers linked by glycosidic bonds.Many beta-glucans are medically important.-Types:The following are glucans:-Alpha:...
(polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
made of many glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
molecules) composed of chains of varying lengths (from 3 to 2000 kilodaltons
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
). It is used medicinally as an antithrombotic
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
(anti-platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
), to reduce blood viscosity
Viscosity
Viscosity is a measure of the resistance of a fluid which is being deformed by either shear or tensile stress. In everyday terms , viscosity is "thickness" or "internal friction". Thus, water is "thin", having a lower viscosity, while honey is "thick", having a higher viscosity...
, and as a volume expander in anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
.
The straight chain consists of α-1,6 glycosidic linkages between glucose molecules, while branches begin from α-1,3 linkages. (For information on the numbering of carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
atom
Atom
The atom is a basic unit of matter that consists of a dense central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...
s in glucose, see the glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
article.) Dextran is synthesized from sucrose by certain lactic-acid bacteria, the best-known being Leuconostoc mesenteroides
Leuconostoc mesenteroides
Leuconostoc mesenteroides is a species of bacteria sometimes associated with fermentation, under conditions of salinity and low temperatures.-External links:*...
and Streptococcus mutans
Streptococcus mutans
Streptococcus mutans is a facultatively aerobic, Gram-positive coccus-shaped bacterium commonly found in the human oral cavity and is a significant contributor to tooth decay.The microbe was first described by J Kilian Clarke in 1924.-Introduction:...
. Dental plaque
Dental plaque
Dental plaque is a biofilm, usually a pale yellow, that develops naturally on the teeth. Like any biofilm, dental plaque is formed by colonizing bacteria trying to attach themselves to a smooth surface...
is rich in dextrans. Dextran is also formed by the lactic acid bacterium Lactobacillus brevis
Lactobacillus brevis
Lactobacillus brevis is a species of lactic acid bacteria. It can be found in many different environments and in fermented foods such as sauerkraut and pickles. It is also one of the most common causes of beer spoilage. Ingestion has been shown to improve human immune function, and it has been...
to create the crystals of tibicos
Tibicos
Tibicos, also known as tibi, water kefir grains, sugar kefir grains, Japanese water crystals and California Bees, and in older literature also known as Bébées, African bees, Ale nuts, Australian bees, Balm of Gilead, Beer seeds, Beer plant, Bees, Ginger Beer plant, Ginger bees, Japanese Beer seeds...
, or water kefir fermented beverage which supposedly has some health benefits.
Dextran was first discovered by Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...
as a microbial product in wine.
Microsurgery uses
These agents are used commonly by microsurgeons to decrease vascular thrombosisThrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
. The antithrombotic effect of dextran is mediated through its binding of erythrocytes, platelets, and vascular endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
, increasing their electronegativity
Electronegativity
Electronegativity, symbol χ , is a chemical property that describes the tendency of an atom or a functional group to attract electrons towards itself. An atom's electronegativity is affected by both its atomic number and the distance that its valence electrons reside from the charged nucleus...
and thus reducing erythrocyte aggregation and platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
adhesiveness. Dextrans also reduce factor VIII-Ag Von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
, thereby decreasing platelet function. Clots formed after administration of dextrans are more easily lysed due to an altered thrombus structure (more evenly distributed platelets with coarser fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
). By inhibiting α-2 antiplasmin, dextran serves as a plasminogen activator and therefore possesses thrombolytic features.
Outside from these features, larger dextrans, which do not pass out of the vessels, are potent osmotic agents, and thus have been used urgently to treat hypovolemia
Hypovolemia
In physiology and medicine, hypovolemia is a state of decreased blood volume; more specifically, decrease in volume of blood plasma...
. The hemodilution caused by volume expansion with dextran use improves blood flow, thus further improving patency of microanastomoses and reducing thrombosis. Still, no difference has been detected in antithrombotic effectiveness in comparison of intraarterial and intravenous administration of dextran.
Dextrans are available in multiple molecular weights ranging from 10,000 Da to 150,000 Da. The larger dextrans are excreted poorly from the kidney and therefore remain in the blood for as long as weeks until they are metabolized. Subsequently, they have prolonged antithrombotic and colloidal effects. In this family, dextran-40 (MW: 40,000 Da), has been the most popular member for anticoagulation
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
therapy. Close to 70% of dextran-40 is excreted in urine within the first 24 hours after intravenous infusion while the remaining 30% will be retained for several more days.
Other medical uses
- It is used in some eye dropEye dropEye drops are saline-containing drops used as a route to administer medication in the eye. Depending on the condition being treated, they may contain steroids, antihistamines, sympathomimetics, beta receptor blockers, parasympathomimetics, parasympatholytics, prostaglandins, non-steroidal...
s as a lubricant, and in certain intravenous fluids to solubilise other factors, e.g. iron (=iron dextran). - Intravenous solutionIntravenous therapyIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
s with dextran function both as volume expanderVolume expanderA volume expander is a type of intravenous therapy that has the function of providing volume for the circulatory system. It may be used for fluid replacement.-Physiology:...
s and means of parenteral nutrition. Such a solution provides an osmotically neutral fluid that once in the body is digested by cells into glucose and free water. It is occasionally used to replace lost bloodBloodBlood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
in emergency situations, when replacement blood is not available, but must be used with caution as it does not provide necessary electrolytes and can cause hyponatremiaHyponatremiaHyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
or other electrolyteElectrolyteIn chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
disturbances. - It also increases blood sugarBlood sugarThe blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
levels.
Laboratory uses
- Dextran is used in the osmotic stress techniqueOsmotic stress techniqueThe osmotic stress technique is a method for measuring the effect of water on biological molecules, particularly enzymes. Just as the properties of molecules can depend on the presence of salts, pH, and temperature, they can depend significantly on the amount of water present...
for applying osmotic pressureOsmotic pressureOsmotic pressure is the pressure which needs to be applied to a solution to prevent the inward flow of water across a semipermeable membrane....
to biological molecules. - It is also used in some size-exclusion chromatography matrices; an example is SephadexSephadexSephadex is a trademark for cross-linked dextran gel used for gel filtration. It was launched by Pharmacia in 1959, after development work by Jerker Porath and Per Flodin. The name is derived from separation Pharmacia dextran. It is normally manufactured in a bead form and most commonly used for...
. - Dextran has also been used in bead form to aid in bioreactor applications.
- Dextran has been used in immobilization in biosensors.
- Dextran preferentially binds to early endosomes; fluorescently-labelled dextran can be used to visualize these endosomes under a fluorescent microscope.
- Dextran can be used as a stabilising coating to protect metal nanoparticles from oxidation and improve biocompatibility.
- Dextran coupled with a fluorescent molecule(such as FITC) can be used to create concentration gradients of diffusible molecules for imaging and allow subsequent characterization of gradient slope.
- Dextran is used to make microcarriers for industrial cell culture
Side effects
Although there are relatively few side-effects associated with dextran use, these side-effects can be very serious. These include anaphylaxisAnaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
, volume overload, pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
, cerebral edema
Cerebral edema
Cerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...
, or platelet dysfunction. An uncommon but significant complication of dextran osmotic effect is acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
. The pathogenesis of this renal failure is the subject of many debates with direct toxic effect on tubules and glomerulus
Glomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
versus intraluminal hyperviscosity being some of the proposed mechanisms. Patients with history of diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, renal insufficiency
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, or vascular disorders are most at risk. Brooks and others recommend the avoidance of dextran therapy in patients with chronic renal insufficiency and CrCl<40 cc per minute.