Blood coagulation, or hemostasis, is necessary to prevent excessive hemorrhage from damaged blood vessels. Under normal conditions, clotting factors in the bloodstream interact with damaged vessels to create a blood clot that plugs the leaking vessel. Obviously, inadequate blood clotting is harmful in that even minor vessel damage can lead to excessive blood loss. Overactive clotting is also detrimental because it will lead to thrombogenesis (i.e., the abnormal formation of blood clots, or thrombi).1 Thrombus formation may lead directly to vessel occlusion and tissue infarction. Also, a piece of a thrombus may dislodge, creating an embolism that causes infarction elsewhere in the body, such as in the lungs or brain.
Consequently, normal hemostasis can be regarded as a balance between too much and too little blood coagulation.2,3 This balance is often disrupted by several factors. Insufficient levels of blood-clotting factors typically cause inadequate clotting, as in patients with hemophilia. Excessive clotting often occurs during prolonged bed rest or when blood flow through vessels is partially obstructed, as in coronary atherosclerosis.
Restoration of normal hemostasis is accomplished through pharmacological methods. Excessive clotting and thrombus formation are rectified by drugs that prevent clot formation (anticoagulants, antiplatelet drugs) or facilitate the removal of previously formed clots (fibrinolytics). Inadequate clotting is resolved by replacing the missing clotting factors or facilitating the synthesis of specific clotting factors.
Hemostasis can also be influenced by hyperlipidemia, which is a chronic and excessive increase in plasma lipids. With hyperlipidemia, cholesterol and other lipids are progressively deposited onto arterial walls, forming plaquelike lesions indicative of atherosclerosis. These atherosclerotic lesions progressively occlude the arterial lumen, and atherosclerotic plaques can suddenly rupture, thus leading to thrombosis and infarction. Atherosclerotic heart disease is one of the leading causes of morbidity and mortality in the United States. Pharmacological methods to lower plasma lipids are often used in conjunction with dietary and lifestyle modifications to treat hyperlipidemia and prevent atherosclerosis.
Drugs that can normalize blood clotting or reduce hyperlipidemia are among the most common medications used clinically, and you will encounter many patients taking these agents. Many patients, in fact, will be treated in therapy for problems relating directly to thrombus formation (e.g., ischemic stroke, myocardial infarction, pulmonary embolism). You will also routinely see individuals with inadequate clotting, such as patients with hemophilia, who are in rehabilitation because of the intrajoint hemorrhaging and other problems associated with this disease. Consequently, the purpose of this chapter is to acquaint you with several common and important groups of drugs used to treat coagulation disorders and hyperlipidemia.
NORMAL MECHANISM OF BLOOD COAGULATION
To understand how various drugs affect hemostasis, it is necessary to review the normal way in which blood clots are formed. The physiological mechanisms involved in hemostasis are outlined in Figure 25-1, with clot formation and breakdown illustrated in the upper ...