Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

Intrinsic and extrinsic pathways

X

Prothrombin

Fibrinogen Fibrin

Xa Anti-thrombin III

Heparin

Thrombin

Inactive complex

Figure 23.2.Actions of heparin. Heparin augments (−→) the formation of the inactive

‘anti-thrombin–thrombin’ complex, while inhibiting ( )factors Xa, IXa, XIa, and XIIa.

Heparins and protamine

Unfractionated heparin

Heparin is an anionic, mucopolysaccharide, organic acid containing many sulphate

residues. It occurs naturally in the liver and mast cell granules and has a variable

molecular weight (5000–25 000 Da).

Uses

Unfractionated heparin is used by continuous intravenous infusion to treat deep

vein thrombosis (DVT), pulmonary embolus (PE), unstable angina and in critical

peripheral arterial occlusion. Subcutaneous administration helps prevent venous

thrombosis peri-operatively and in the critically ill. It is also used in the priming

of extracorporeal circuits. There has been limited use in disseminated intravascular

coagulation (DIC).

Mechanism of action

When anti-thrombin III combines with thrombin an inactive ‘anti-thrombin–

thrombin’ complex is formed (Figure23.2). The rate of formation of this complex

is increased thousand-fold by heparin. At low concentrations factor Xa is inhibited,

while factors IXa, XIa and XIIa are progressively inhibited as heparin concentra-

tions rise. Platelet aggregation becomes inhibited at high concentrations and plasma

triglyceride levels are lowered due to the release of a lipoprotein lipase from tissues,

which reduces plasma turbidity.

Side effects


Haemorrhage – this is the most common side effect and is due to a relative overdose.