210 ANTICOAGULANTS AND ANTIPLATELETDRUGS
FURTHER READING
Hirsh J, O’Donnell M, Weitz JI. New anticoagulants. Blood2005; 105 :
453–63.
Patrono C, Coller B, FitzGerald GA, Hirsh J, Roth G. Platelet-active
drugs: The relationships among dose, effectiveness, and side
effects. Chest2004; 126 : 234S-64S.
Pengo V. New trends in anticoagulant treatments. Lupus2005; 14 :
789–93.
Ringleb PA. Thrombolytics, anticoagulants, and antiplatelet agents.
Stroke2006; 37 : 312–13.
Steinhubl SR, Moliterno DJ. The role of the platelet in the pathogen-
esis of atherothrombosis. American Journal of Cardiovascular Drugs
2005; 5 : 399–408.Key points
Thrombosis- Thrombosis occurs when excessive clotting occurs in
blood vessels, thereby occluding them, and thrombi
consist of platelets and fibrin. - In general, arterial thrombosis is prevented by
antiplatelet therapy and can be treated by fibrinolytic
therapy with or without concomitant anticoagulation. - The principal antiplatelet agents in clinical use are
aspirin and clopidogrel. Aspirin inhibits platelet
thromboxane A 2 formation (by inhibition of cyclo-
oxygenase), clopidogrel (through hepatic formation of
its active metabolite) inhibits platelet ADP receptors. - The main adverse effects of aspirin are on the gastro-
intestinal tract, the most severe of these being gastro-
intestinal bleeding. These effects are dose related and
can be countered by suppression of acid secretion by
the stomach if necessary. - Venous and cardiac thromboembolic disease (e.g. in the
context of atrial fibrillation) are best prevented by
anticoagulant therapy. - The principal anticoagulants used clinically are
heparin or, more commonly nowadays low-
molecular-weight heparin, and warfarin. Heparin
and low-molecular-weight heparin are given
parenterally, warfarin is administered orally. - Low-molecular-weight heparins are effective and
convenient. They do not require routine
haematological monitoring (unlike heparin, which
requires frequent monitoring of the APTT), can be
given subcutaneously once a day and patients can be
taught to administer them at home. - Warfarin and other coumadins work by interfering with
the action of vitamin K on factors II, VII, IX and X.
Monitoring is by measurement of the international
normalized ratio (INR). There is very wide variation in
individual dosage requirements. - Drug interactions with warfarin are common and
important, and include interactions with
anticonvulsants, antibiotics, sulphonylureas and non-
steroidal anti-inflammatory drugs.