Read an Excerpt
The Coumadin (Warfarin) Help Book
Anticoagulation Therapy to Prevent and Manage Strokes, Heart Attacks, and Other Vascular Conditions
By Diana M. Schneider
Copyright © 2008
All right reserved.
Chapter One What Is an Anticoagulant, and Why Is Controlling Blood Clotting So Important?
A BLOOD CLOT IS the gelatinous mass that normally forms whenever we experience any type of cut or injury, and normal blood clotting is essential to life. However, blood clots also can develop as the result of a number of medical conditions that involve the heart, lungs, and vascular system. When they form at the wrong time and in the wrong place, clots can lead to a heart attack, stroke, or pulmonary embolism, so it is extremely important that they be prevented.
Anti means against, and coagulant refers to blood clotting, so an anticoagulant helps to prevent clots from forming in the blood. Coumadin[R] and generic warfarin are long-acting oral anticoagulants, as distinct from rapid- and short-acting anticoagulants that must be injected.
Before we can discuss the conditions that lead to unwanted clot formation, the serious conditions that result, and how anticoagulants work, you need to understand a bit about the circulatory system and the process of blood clotting.
The Circulatory System
Figure 1.1 shows the pathway that blood takes through the circulatory system, which includes the heart, lungs, and blood vessels. The system is essentially a large double loop-one between the heart and lungs, and one involving the heart and general circulation. It provides oxygenated blood to the tissues of the body, and then returns this blood to the heart when it is depleted of oxygen, and the cycle begins again.
The right side of this diagram includes the left side of the heart (remember, you are looking at this "head on") and the arterial system that delivers blood to all the tissues of the body, called the systemic circulation. The blood it contains has been provided with oxygen by the lungs. After oxygen is removed from the arterial part of the system by the tissues of the body, it enters the venous system. This blood enters the right side of the heart, where it is pumped to the lungs to be oxygenated. It then enters the left side of the heart to be once again pumped into the arterial system, repeating the cycle. This pumping system depends on a complex system of nerves that runs throughout the heart, causing its muscles to contract in just the right sequence to allow for smooth and continuous pumping.
This smoothly functioning system can develop a number of problems, many of which result in an increased tendency to form clots. Anticoagulants are prescribed for people who are at increased risk for developing harmful blood clots and for those who have already experienced a problem due to clots. Individuals at risk for developing clots include people who have the irregular heart rhythm called atrial fibrillation (AF), a mechanical heart valve, and those with disorders of the clotting system itself. People with a history of developing harmful clots have experienced a stroke, a heart attack, a clot that traveled to the lung (pulmonary embolism or PE), or a blood clot in the leg (deep venous thrombosis or DVT).
The number of people who take the anticoagulant medications Coumadin or warfarin has increased rapidly, because the number of conditions for which they have been shown to be effective has increased. When clots do occur, they reduce blood flow to the organs whose blood supply is provided by the vessel in which the clot formed. A stroke results when a blood vessel leading to a portion of the brain is blocked; a heart attack occurs when a blood vessel leading to the heart is blocked; and a pulmonary embolus occurs when a clot formed in the right side of the heart lodges in the lungs.
What Controls Blood Clotting?
Blood clotting after a cut or injury is essential to life. The process by which clotting occurs is called coagulation, and the total process of blood clotting followed by the clot dissolving and repair of the injured tissue is termed hemostasis.
Hemostasis consists of four steps:
* The blood vessels in the area of the injury constrict, limiting blood flow to the area that has been injured.
* Platelets (cells that circulate in the blood) are activated by a substance called thrombin, which is released when an injury occurs. The platelets then migrate into the area of injury, where they form a loose plug. These platelets then clump by binding to collagen, which is released by damaged blood vessels in the injured area. The platelets then release additional substances that are important for coagulation.
* To stabilize the initially loose platelet plug, a fibrin mesh (the clot) forms around and within the plug.
* Finally, when sufficient healing has occurred, the clot dissolves and normal blood flow to the injured area can resume.
The process of clot formation involves a group of proteins called clotting factors, which are made in the liver. The pathway through which clotting occurs-the coagulation cascade-is shown schematically in Figure 1.2. It is not necessary to understand the details of this complex process, only that Coumadin or warfarin affects the activity of some of the proteins involved, and that this in turn prevents the formation of clots at the wrong time and in the wrong place. The drugs do so by inhibiting the activity of the vitamin K-dependent clotting factors involved in the clotting cascade. The involvement of so many substances and the complexity of the clotting cascade are the reasons why the system is so sensitive to the content of vitamin K in your diet, and why it can be difficult to maintain a constant level of clotting when using an anticoagulant.
How Is Vitamin K Involved in the Clotting Process?
Vitamins are nutrients that are required in very small amounts in order for essential metabolic reactions to occur in the body. All vitamins act as catalysts in chemical reactions that are essential to life. In this role, they bind to enzymes and are termed cofactors. The "K" in vitamin K is from the Danish word for coagulation, "koagulering," in honor of the Danish scientist who discovered it.
Vitamin K is an essential cofactor for the action of an enzyme that allows substances needed in the clotting pathway to bind calcium, without which clotting cannot occur. Of particular importance is its role in the synthesis of prothrombin in the liver. Remember, your regular blood tests while on Coumadin measure "prothrombin time" or PT; the INR is a normalized version of this measurement. You can see from Figure 1.2 that prothrombin and its derivative molecule thrombin are central components in the clotting process, so your INR actually measures the activity of this essential component of the clotting process.
Coumadin and warfarin block the availability of vitamin K and limit production of the clotting factors. As a result, it takes longer for the blood to clot.
The interaction between vitamin K and anticoagulants is competitive in nature. The more vitamin K in the diet, the less effective Coumadin or warfarin becomes. However, as long as your diet remains constant with respect to vitamin K, the dose of anticoagulant can be adjusted to overcome this effect.
Only small amounts of vitamin K are stored in the body, and it must be constantly replenished through the diet. Coumadin and warfarin prevent its reuse, essentially causing a deficiency of the vitamin and thus inhibiting clot formation. The medication does this by inhibiting two important chemical reactions in the clotting system. So, a sort of "push-pull" interaction occurs between the anticoagulant medication and vitamin K. The trick is to keep them in balance, which you probably already know since you are reading this book!
Sources of Vitamin K
There are actually two sources of vitamin K. One-called vitamin K1-is probably already familiar to you because of the need to maintain a constant level of leafy greens and other vitamin K-containing foods in your diet. The other-vitamin K2-is made by bacteria in the gut. The K2 form can be affected by illnesses such as influenza (the "flu"), which can deplete the level of these helpful bacteria. Vitamin K1 is manufactured for medicinal use as Mephyton[R], and is occasionally used to rapidly decrease the rate of clotting should your INR become extremely high or should you need emergency surgery.
The next two chapters discuss what happens when clots form in the vascular system, and what conditions can lead to clot formation.
Chapter Two The Consequences of Abnormal Clot Formation: Stroke, Heart Attacks, and More
WHEN CLOTS FORM anywhere in the blood vessels of the vascular system, they can break away from the vessel wall and travel through the vascular system. Eventually, they lodge in blood vessels that are smaller than the size of the clot. Most often, this means the brain, heart tissue, or lungs, where they cause strokes, heart attacks, or pulmonary emboli. This can be fatal, or it can result in significant disability. What are these conditions, and why is it so important to do everything possible to avoid them?
Stroke is the third largest cause of death annually in the United States, after heart disease and cancer, and the leading cause of adult disability. Over 5 million Americans have survived a stroke. Worldwide, approximately 10 percent of all deaths are due to stroke. The Centers for Disease Control puts the number of new or recurrent strokes at about 700,000 each year, and the annual number of deaths at 150,000.
The term stroke, also referred to as a cerebrovascular accident (CVA), is used for any rapid loss of brain function that occurs as the result of a problem in the vessels that supply blood to the brain. This can be due either to ischemia-a lack of blood supply and oxygen caused by a blood clot, or to a hemorrhage-a leakage of blood from these vessels. Eighty percent of all strokes are of the ischemic type; 20 percent are hemorrhagic.
Both types of stroke are important for people who take Coumadin[R] or warfarin. The most common reason for taking these anticoagulants is to prevent the development of a blood clot that can cause an ischemic stroke by blocking a blood vessel. They are prescribed to people at high risk for developing blood clots, and to those who have already experienced a stroke.
Maintaining the INR in the desired therapeutic range is critical to avoiding both problems. The risk of stroke doubles as the INR decreases from 2.0 to 1.7 in people with atrial fibrillation (AF) whose target range INR is 2.0 to 3.0, and it more than doubles again if the INR is reduced to 1.4.
Conversely, bleeding from a hemorrhagic stroke is one of the most dangerous consequences of too high a level of anticoagulant and a seriously increased INR. To put "seriously increased" into perspective, an INR of 4.0 nearly doubles the risk of a bleeding incident over that with an INR of 3.0 or less-and the risk of a serious bleed increases nearly sevenfold with an INR of over 6.0.
High-risk cardiac causes of ischemic stroke include AF, rheumatic disease of the mitral or aortic valve, and artificial heart valves. In people who have AF without any damage to the heart valves, anticoagulation can reduce the risk of stroke by 60 percent.
A major focus in treating people with these conditions is called secondary prevention-actions that can be taken to reduce the risk of a stroke in those who already have diseases or risk factors that are known to cause stroke, as well as in people who have already had one or more strokes. Medication or drug therapy is the most common method of stroke prevention. Aspirin-usually low-dose or "baby" aspirin-is often recommended. People with abnormalities of the heart that put them at risk for developing an ischemic stroke, or who have already had one, often require anticoagulation with medications such as Coumadin or warfarin.
See the Resources at the end of this book for information on websites that have detailed information about stroke.
Over 25 million people in the United States have heart disease, and nearly a million people have a heart attack-an acute myocardial infarction-each year. Heart disease is the leading cause of death in the United States-one in five deaths, or over 650,000 annually. Worldwide, over 12 percent of deaths are due to ischemic heart disease.
A heart attack occurs when the blood supply to the heart is interrupted. A blood clot is the most common cause of a blocked coronary artery. Usually, the artery is already partially narrowed by an atherosclerotic plaque. This can rupture or tear, narrowing the artery still further and making blockage by a clot more likely. The ruptured plaque material reduces the flow of blood through the artery, and it also releases substances that make platelets stickier, further encouraging clots to form. The resulting ischemia or oxygen shortage causes damage and potential death of heart tissue. One of the more important risk factors for a heart attack is an arrhythmia, one of the reasons that AF is normally treated with an oral anticoagulant.
Following a heart attack, the injured heart tissue conducts electrical impulses more slowly than normal heart tissue. The imbalance between normal conduction in the undamaged tissue and slowed conduction in the damaged area is believed to be the cause of many of the arrhythmias that occur following a heart attack. The most serious of these is ventricular fibrillation, an extremely fast and chaotic heart rhythm that is the leading cause of sudden cardiac death.
A substantial number of people who have had a heart attack subsequently experience clot formation in the left ventricle, as the result of damaged heart tissue. These clots, or parts of them, can break off and travel through the bloodstream; if they travel to the brain, they will cause a stroke.
Anticoagulants are commonly prescribed to help prevent clot formation after a heart attack, especially if the heart attack was massive, or if areas of the heart are not beating well. An anticoagulant is usually taken for three to six months after a heart attack, often maintaining the INR at 2.5 to 3.5.
For more detailed information about myocardial infarction, see the Resources section at the end of this book.
Venous Thromboembolism: Deep Vein Thrombosis and Pulmonary Embolism
An estimated 2 million people in the United States develop a venous thromboembolism (VTE) each year. About 600,000 are hospitalized, and 60,000 die.
The term VTE refers both to deep vein thrombosis (DVT) and pulmonary embolism (PE). A venous thrombosis is a blood clot that forms in the venous system, most commonly in the legs. It can cause calf pain and tenderness, sometimes accompanied by redness, warmth, and swelling of the leg. However, some people are not aware of any symptoms.
Although it can occur in young, otherwise healthy adults, DVT most frequently occurs following trauma, major surgery, prolonged immobility (including airline travel), or in people who have a clotting disorder. Other risk factors include obesity, smoking, and hypertension. Chronic medical conditions such as heart failure and cancer, as well as oral contraceptives and hormone replacement therapy (HRT), also increase the risk of DVT. Any risk factor for DVT also increases the risk that the venous clot will dislodge and migrate to the lung circulation. This happens in up to 15 percent of all DVTs.
Pulmonary embolism most often occurs when one or more of these dislodged clots lodges in the pulmonary artery or one of its branches, causing a partial or complete obstruction of blood flow to a portion of lung tissue. Symptoms can include the sudden onset of shortness of breath, rapid breathing, chest pain, and coughing. More severe cases might be associated with a bluish discoloration, usually of the lips and fingers (cyanosis), collapse, and circulatory instability. About 15 percent of all cases of sudden death are attributable to PE.
The duration of anticoagulant therapy following a VTE varies, depending on whether it is the first time a clot has occurred or if they have occurred previously, the location of the clot(s), and any medical conditions that increase your chances of subsequent clot formation. However, you will require anticoagulant therapy for a minimum of three to six months.
Excerpted from The Coumadin (Warfarin) Help Book by Diana M. Schneider Copyright © 2008 by DiaMed, LLC. Excerpted by permission.
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