A Textbook of Clinical Pharmacology and Therapeutics

●Introduction 204

●Pathophysiology of thrombosis 204

●Anticoagulants 205

●Antiplatelet drugs 208

●Anticoagulants in pregnancy and puerperium 209

CHAPTER 30

ANTICOAGULANTS AND

ANTIPLATELET DRUGS

INTRODUCTION

The treatment and prevention of thrombosis involves three
classes of drugs, namely anticoagulants, antiplatelet drugs and
fibrinolytics. Fibrinolytics are discussed in Chapter 29. The clini-
cal pharmacology of the anticoagulants and antiplatelet drugs is
described in the present chapter. Anticoagulants inhibit the
coagulation cascade. Their main use is to treat and prevent
venous thrombosis (‘red thrombus’) and its major complication,
pulmonary embolism, whereas antiplatelet drugs are mainly
used in the treatment of platelet-rich coronary and other arterial
thrombi (‘white thrombus’). Nevertheless, there are many links
between platelet activation and the coagulation cascade, so it is
not surprising that anticoagulants can also have beneficial effects
in the prevention of coronary artery disease, or that antiplatelet
drugs have some (albeit a minor) effect on venous thrombosis.

PATHOPHYSIOLOGY OF THROMBOSIS

Haemostasis is achieved by an exquisitely balanced series
of interlocking control systems involving both positive

feedbacks – permitting very rapid responses to the threat of

haemorrhage following sharp injury – and negative feedbacks –

to prevent the clotting mechanism from running out of control

and causing thrombus to propagate throughout the circula-

tion following haemostasis at a site of injury. In addition there

is an endogenous fibrinolytic system that dissolves thrombus

that has done its job. Not surprisingly, these systems some-

times go wrong, resulting in bleeding disorders, such as

haemophilia or thrombocytopenic purpura, or in thrombosis.

Thrombosis is caused by injury to the vessel wall, stasis

and activation of coagulation processes (platelets and the

coagulation cascade), these three processes being referred to

as Virchow’s triad (Figure 30.1). Coagulation involves the

sequential activation of a cascade of clotting factors which

amplifies a small initial event to produce a macroscopic plug

of fibrin. Each factor is present in blood as an inactive zymo-

gen. Several of these factors (II, VII, IX and X) are glycopro-

teins which contain γ carboxyglutamic acid residues introduced

by post-translational modification. This process requires vita-

min K. After activation (indicated by the letter ‘a’ after the

Roman numeral that designates the zymogen), several of the

factors acquire proteolytic activity. Thrombin and factors IXa,

Xa, XIa and XIIa are all serine proteases. Oestrogens increase

IXa

Thrombin Fibrin Endothelium Subendothelium

Platelet

Factor VIII molecule

Von Willebrand

factor

Xa

Figure 30.1:Interactions between the clotting system,

platelets and the blood vessel wall.