Dextran

Dextran is a complex, branched polysaccharide made of many glucose molecules joined into chains of varying lengths (from 10 to 150 kilodaltons), used as an antithrombotic (anti-platelet), and to reduce blood viscosity.

The straight chain consists of α1->6 glycosidic linkages between glucose molecules, while branches begin from α1->4 linkages (and in some cases, α1->2 and α1->3 linkages as well). (For information on the numbering of carbon atoms 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.

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Uses

Microsurgery uses

These agents are used commonly by microsurgeons to decrease vascular thrombosis. 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.

Other medical uses

• It is used in some eye drops as a lubricant, and in certain intravenous fluids to solubilise other factors, e.g. iron (=iron dextran).
• Dextran in intravenous 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 blood 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 hyponatremia or other electrolyte disturbances.
• It also increases blood sugar levels.

Laboratory uses

Dextran is used in the osmotic stress technique for applying osmotic pressure to biological molecules.

It is also used in some size-exclusion chromatography matrices; an example is Sephadex®.

Dextran has also been used in bead form to aid in bioreactor applications.

Dextran has been used in immobilization in Biosensors.

Side effects

Although there are relatively few side-effects associated with dextran use, these side-effects can be very serious. These include anaphylaxis, 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.