Heparin Sodium

Heparin is an injectable anticoagulant, nowadays usually made synthetically. It is used both as an anticoagulant in people, and in various medical devices such as test tubes and extracorporal circulation devices such as renal dialysis machines. Heparin was originally isolated from liver cells, hence its name (hepato- means "of the liver"). Scientists were looking for an anticoagulant that could work safely in humans and researchers in Johns Hopkins found a compound extracted from liver that could work. Heparin sodium and calcium occur as white or pale-colored, amorphous, hygroscopic powders having a faint odor. Both are soluble in water and practically insoluble in alcohol; the commercial injections have a pH of 5-7.5. Heparin potency is expressed in terms of USP Heparin units and values are obtained by comparing against a standard reference from the USP.

The key structural unit of heparin is a unique pentasaccharide sequence. This sequence consists of three D-glucosamine and two uronic acid residues. The central D-glucosamine residue contains a unique 3-O-sulfate moiety that is rare outside of this sequence. Four sulfate groups on the D-glucosamines, encircled in the figure below, are found to be critical for retaining high anticoagulant activity. Elimination of any one of them results in a dramatic reduction in the anticoagulant activity. Removal of the unique 3-O-sulate group results in complete loss of the anticoagulant activity. Removal of sulfate groups other than the critical ones seems to not affect the anticoagulant activity.

Heparin is a mucopolysaccharide with a molecular weight ranging from 6,000 to 40,000 Da. The average molecular of most commercial heparin preparations is in the range of 12,000 - 15,000. The polymeric chain is composed of repeating disaccharide unit of D-glucosamine and uronic acid linked by 1-->4 interglycosidic bond. The uronic acid residue could be either D-glucuronic acid or L-iduronic acid. Few hydroxyl groups on each of these monosaccharide residues may be sulfated giving rise to a polymer with that is highly negatively charged. Heparin works by potentiating the action of antithrombin III, as it is similar to the heparan sulfate proteoglycans which are naturally present on the cell membrane of the endothelium. Because antithrombin III inactivates many coagulation proteins, the process of coagulation will, slow down. In case of overdose, a chemical protamine can be given to counteract the heparin action. The effects of heparin are measured in the lab by the APTT, (the time it takes the blood plasma to clot).

Heparin sodium is reportedly compatible with the following intravenous solutions and drugs: amino acids 4.25%-dextrose 25%, dextrose-Ringer’s combinations, dextrose-lactated Ringer’s solutions, fat emulsion 10%, Ringer’s injection, Normosol R, aminophylline, amphotericin B w/ or w/o hydrocortisone sodium phosphate, ascorbic acid injection, bleomycin sulfate, calcium gluconate, cephapirin sodium, chloramphenicol sodium succinate, clindamycin phosphate, dimenhydrinate, dopamine HCl, erythromycin gluceptate, isoproterenol HCl, lidocaine HCl, methylprednisolone sodium succinate, metronidazole with sodium succinate, nafcillin sodium, norepinephrine bitartrate, potassium chloride, prednisolone sodium succinate, promazine HCl, sodium bicarbonate, verapamil HCl and vitamin B-complex w/ or w/o vitamin C. Heparin sodium is reported incompatible with the following solutions or drugs: sodium lactate 1/6 M, amikacin sulfate, chlorpromazine HCl, codeine phosphate, cytarabine, daunorubicin HCl, diazepam, doxorubicin HCl, droperidol HCl w/ & w/o fentanyl citrate, erythromycin lactobionate, gentamicin sulfate, hyaluronidase, kanamycin sulfate, levorphanol bitartrate, meperidine HCl, methadone HCl, morphine sulfate, pentazocine lactate, phenytoin sodium, polymyxin B sulfate, streptomycin sulfate and vancomycin HCl.