Low molecular weight dextran

S Smitha Prabhu

 Department of Dermatology and Venereology, Medical College Hospital, Calicut - 673 008, India

Correspondence Address:
S Smitha Prabhu
Department of Dermatology and Venereology, Medical College Hospital, Calicut - 673 008
India

Syn: Lomodex, Rheomacrodex, Gentran 40, Rheotran[1]

Dextran (C6H1005)n is a gum produced from cane or beet sugar where it is formed by the action of a contaminating bacterium Leuconostoc mesenteroides. Native dextran is a polymer of glucose with a molecular weight around 40 million; from which is prepared relatively lower molecular weight dextrans: high molecular weight (HMW) dextran of molecular weight 70000 and Low molecular weight (LMW) dextran, which is a mixture of dextrose polymers with an average molecular weight of 40000 (i.e., 10000-70000), in which the glucosidic linkage is of the a (1?6) type.[1]

Mechanism of production:

Sucrose is acted upon by the bacterium Leuconostoc mesenteroides B512 and is converted to crude high molecular weight dextran which is then hydrolyzed and fractionated to obtain a molecular weight of 40000, or alternatively, low molecular weight dextran is obtained by degrading dextran with acid and purifying the correct sized dextran from the resulting mixture.[2]

Properties

It is an amorphous, odorless and tasteless powder. 10% solution of dextran 40 in 5% dextrose in water darkens slightly over long storage period. Darkening is aggravated by increased ambient temperature. Low molecular weight dextran is excreted by the kidneys. The half-life of dextran is about 24 hours. Renal insufficiency increases the half-life of LMW dextran by a factor of 6.[3]

Mechanism of action and effects on systems

1. It lowers viscosity of blood and improves flow. In part, the improvement in flow is the result of hemodilution.

2. Platelet adhesion is decreased.

3. It decreases serum fibrinogen and clotting factors.

4. Decreases rouleux formation by RBCs and has an antisludging effect on blood.

5. Dextran 40 inhibits adhesion of T- lymphocytes to endothelial cells?

6. Low molecular weight dextran firmly adheres to circulating RBCs in vivo. It also attaches itself to arterial walls, which have been damaged by physical rather than chemical bonding. This molecular coating may sterically prevent the critical concentration of substances necessary for clotting or may insulate or counter transmural thrombogenic potentials. This is the mechanism proposed of its action in Raynaud′s phenomenon and other arterial diseases.[8]

Uses

Dermatological conditions:

1. Deep vein thrombosis and thrombophlebitis

2. Raynaud′s phenomenon[4]

3. Anti phospholipid syndrome - impending digital gangrene

4. Frost bite.[3]

5. Cutaneous cholesterol emboli

6. Livedo reticularis with ulceration[9]

Other Uses

1. Isotonic solution is used to prime pumps or improve flow in surgery requiring cardiopulmonary bypass.

2. As prophylactic for thrombosis and thromboembolism during and after surgery.

3. To decrease coagulopathies during shock - used only for a short period of time. (Otherwise dextran 40 is seldom used in shock because of short duration in the body and frequent adverse effects)

4. Stroke

5. Improvement of circulation in transplant and graft procedures.

6. As a plasma expander.

Method of administration

As a 10% intravenous solution in 5% dextrose or in Normal saline. First inject 20 ml IV over 3 to 5 minutes to decrease the risk of anaphylaxis. Then infuse 20-30 ml per hour up to a maximum of 2 to 3 litres per day.

In Raynaud′s phenomenon: infuse 500--1000 ml over 4 - 6 hours on day 1. 500 ml on day 2. then on alternate days for 10 days.[5]

Side effects

1. Acute renal failure: There is accumulation of low molecular weight fraction in the renal tubules, which induces vacuolization of proximal tubular cells. It may also cause edema and disrupt integrity of the capillary membrane. All these effects are maximized especially when there is pre-existing renal impairment.

2. Bleeding tendency: It decreases viscosity of blood and platelet adhesion, therefore causing increased bleeding, especially in people with pre-existing coagulopathies, and in those who are on concomitant anti-platelet drugs.

3. Anaphylaxis: by histamine release. Occurs in 1-5% of cases. Manifests as urticaria, wheezing, and tightness of chest.[6]

4. Nausea and vomiting

5. Hypotension

6. Bleeding tendency - especially if on concomitant anti platelet drugs.

Contra - indications for use

1. Congestive cardiac failure

2. Severe coagulative disorders

3. Hypervoluemic conditions

4. Hypersensitivity to dextran

5. Severe dehydration

Precautions

1. Dextran 40 interferes with cross matching of blood, especially when enzyme methods are used.

2. It interferes with some tests of renal and hepatic function and with assays for blood sugar in which acid hydrolytic method is used.

3. Adequate hydration is to be ensured before starting the patient on low molecular weight dextran.

4. Low specific gravity of urine indicates impaired renal excretion of LMW dextran, and it should be discontinued.

5. Monitoring of serum osmolarity is necessary. If serum osmolarity is> 300 m Osm/I, LMW dextran should be discontinued.

6. Dose should never exceed more than 10% of the blood volume.

7. Precautions to guard against renal failure.[2]

• Do not infuse more than 20 ml/ kg per day.
• Do not give if the urine output is less than 1500 ml per day or if the blood urea is 60 mg/ml or higher.
• Do not give any more if the urine output drops or the specific gravity of the urine rises above 1045 during administration. In such cases try to maintain a high urine output by using diuretics and a high fluid intake.

Preparations available

Inj 10% in 5% dextrose solution, 500 ml.

Inj 10% in 0.9% sodium chloride solution, 500 ml.

Dextran can be stored for up to 10 years and is relatively cheap.

Future uses

1. In cystic fibrosis - to decrease the viscid mucus.

2. It may be useful for therapeutic intervention in diseases associated with enhanced T-lymphocyte binding to microvascular endothelium.

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