A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

210 ANTICOAGULANTS AND ANTIPLATELET DRUGS
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 cyclooxygenase),
clopidogrel (through hepatic formation of
its active metabolite) inhibits platelet ADP receptors.
• The main adverse effects of aspirin are on the gastrointestinal
tract, the most severe of these being gastrointestinal
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 lowmolecular-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 nonsteroidal
anti-inflammatory drugs.
FURTHER READING
Hirsh J, O’Donnell M, Weitz JI. New anticoagulants. Blood 2005; 105:
453–63.
Patrono C, Coller B, FitzGerald GA, Hirsh J, Roth G. Platelet-active
drugs: The relationships among dose, effectiveness, and side
effects. Chest 2004; 126: 234S-64S.
Pengo V. New trends in anticoagulant treatments. Lupus 2005; 14:
789–93.
Ringleb PA. Thrombolytics, anticoagulants, and antiplatelet agents.
Stroke 2006; 37: 312–13.
Steinhubl SR, Moliterno DJ. The role of the platelet in the pathogenesis
of atherothrombosis. American Journal of Cardiovascular Drugs
2005; 5: 399–408.