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Chapter 34: Drugs Used in Coagulation Disorders

INTRODUCTION

The drugs used in clotting and bleeding disorders fall into two major groups: (1) drugs used to decrease clotting or dissolve clots already present in patients at risk for vascular occlusion and (2) drugs used to increase clotting in patients with clotting deficiencies. The first group, the anticlotting drugs, includes some of the most commonly used drugs in the United States. Anticlotting drugs are used in the treatment and prevention of myocardial infarction and other acute coronary syndromes, ischemic stroke in patients with atrial fibrillation, and deep vein thrombosis (DVT). Within the anticlotting group, the anticoagulant and thrombolytic drugs are effective in treatment of both venous and arterial thrombosis, whereas antiplatelet drugs are useful only for treatment of arterial disease.

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High-Yield Terms to Learn
Activated partial thromboplastin time (aPTT) test Laboratory test used to monitor the anticoagulant effect of unfractionated heparin and direct thrombin inhibitors; prolonged when drug effect is adequate
Antithrombin III An endogenous anticlotting protein that irreversibly inactivates thrombin and factor Xa. Its enzymatic action is markedly accelerated by the heparins
Clotting cascade System of serine proteases and substrates in the blood that provides rapid generation of clotting factors resulting in a fibrin clot, in response to blood vessel damage
Glycoprotein IIb/IIIa (GPIIb/IIIa) A protein complex on the surface of platelets. When activated, it aggregates platelets primarily by binding to fibrin. Endogenous factors including thromboxane A2, ADP, and serotonin initiate a signaling cascade that activates GPIIb/IIIa
Heparin-induced thrombocytopenia (HIT) A hypercoagulable state plus thrombocytopenia that occurs in a small number of individuals treated with unfractionated heparin
International Normalized Ratio (INR) Measured coagulation time in PT test expressed as ratio to international standard. Ratio of one is normal coagulation time, anticoagulation increases ratio to greater than one
LMW heparins Fractionated preparations of heparin of molecular weight 2000–6000. Unfractionated heparin has a molecular weight range of 15,000–30,000
Prothrombin time (PT) test Laboratory test used to monitor the anticoagulant effect of warfarin; prolonged when drug effect is adequate

ANTICOAGULANTS

A. Classification

Anticoagulants inhibit the formation of fibrin clots. Three major types of anticoagulants are available: heparin and related products, which must be used parenterally; direct thrombin and factor X inhibitors, which are used parenterally and orally; and the orally active coumarin derivatives (eg, warfarin). Comparative properties of the heparins and warfarin are shown in Table 34–1.

TABLE 34–1Properties of heparins and warfarin.
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TABLE 34–1 Properties of heparins and warfarin.
Property Heparins Warfarin
Structure Large acidic polysaccharide polymers Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (minutes) Slow (days); limited by half-lives of preexisting normal factors
Mechanism of action Activate antithrombin III, which inactivates coagulation factors including thrombin and factor Xa Impairs post-translational ...

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