These agents differ in the way they work,
their potency (how strongly they prevent clumping), how rapidly they work, and
their cost.
What are platelets?
Platelets are particles (actually, remnants of cells) circulating in the
blood that are needed in order for blood clots to form. Platelets initiate the
formation of blood clots by sticking together (clumping or aggregating), a
process called platelet aggregation.
Clumps of platelets then are further bound together by a protein (fibrin) formed by clotting factors present in the blood.
The clumps of platelets and fibrin make up the blood clot.
Blood clots are important because they stop bleeding (for example, a cut or
laceration on the skin). When bleeding occurs from a cut, platelets become activated and form a network by attaching to the
blood vessel wall at the site
of bleeding, and by also attracting other clotting factors in the blood (such as
fibrin) to stop ongoing bleeding rapidly.
However, if a blood clot forms inside an artery, it blocks the
flow of blood to the tissue that the artery supplies, which can damage the
tissue. For example, a blood clot that forms in a coronary artery supplying
blood to the muscle of the heart causes a
heart attack, and a blood clot that
forms in an artery supplying blood to the brain causes a stroke.
How do antiplatelet agents work?
Aspirin
Aspirin prevents blood from clotting by blocking the production by platelets
of thromboxane A-2, the
chemical that causes platelets to clump. Aspirin accomplishes this by inhibiting
the enzyme cyclo-oxygenase-1 (COX-1) that
produces thromboxane A-2. While other NSAIDs also inhibit the COX-1 enzyme,
aspirin is the preferred NSAID for use as an antiplatelet agent because its
inhibition of the COX-1 enzyme lasts much longer than the other NSAIDs
(aspirin's antiplatelet effect lasts days while the other NSAIDs' antiplatelet
effects last only hours).
Thienopyridines
In addition to thromboxane A-2, platelets also produce adenosine diphosphate
(ADP). When ADP attaches to receptors on the surface of platelets, the platelets
clump. The thienopyridines, for example,
ticlopidine (Ticlid) and clopidogrel
(Plavix), block the ADP receptor. Blocking the ADP receptor prevents ADP from
attaching to the receptor and the platelets from clumping.
Glycoprotein IIb/IIIa inhibitors
The glycoprotein IIb/IIIa inhibitors, such as
abciximab
(Reopro) and eptifibatide (Integrilin), prevent clumping by inhibiting a
different receptor on the surface of platelets, the receptor for glycoprotein
IIb/IIIa. The glycoprotein IIb/IIIa inhibitors that are approved by the FDA must be given
intravenously (in the veins).
What is the relative potency of the antiplatelet agents?
Since aspirin blocks only one of the several pathways by
which platelet aggregation can occur, aspirin is a weak antiplatelet agent
because platelet aggregation can be stimulated via another pathway.
Since
glycoprotein IIb/IIIa inhibitors block the final common pathway for platelet
aggregation (platelet aggregation is blocked regardless of the nature of the initial stimuli),
glycoprotein IIb/IIIa inhibitors are the most potent antiplatelet agents. The
maximal antiplatelet effect of glycoprotein IIb/IIIa inhibitors is approximately
nine times that of aspirin.
The maximal antiplatelet effect of thienopyridines is
in between that of aspirin and the glycoprotein IIb/IIIa inhibitors.
How quickly do antiplatelet agents work?
Aspirin
When aspirin is given in low doses (75 mg/day), the
complete inhibition of the COX-1 enzyme and hence maximal antiplatelet effect
may take several days. At a dose of 160-325 mg/day, the maximal antiplatelet
effect of aspirin occurs within 30 minutes. Thus, aspirin at low doses (75-150
mg/day) is used for the long term prevention of heart attacks and strokes,
whereas moderate doses (160-325 mg/day) of aspirin are given in situations where
an immediate anti-clotting effects are needed (such as in the treatment of acute
heart
attacks and unstable angina).
Thienopyridines
Like aspirin, the onset of action of clopidogrel (Plavix) is dose related.
Maximal antiplatelet effect occurs several days after initiation of clopidogrel
(75 mg/daily), but can occur within hours after larger doses of 300 or 600 mg.
Therefore, larger doses of clopidogrel are used initially when immediate
antiplatelet actions are needed (such as after placement of intracoronary
stents) while the lower doses are used as maintenance.
Glycoprotein IIb/IIIa inhibitors
The glycoprotein IIb/IIIa inhibitors have a rapid onset of
action. Their maximal antiplatelet effect occur within minutes after an
intravenous infusion, and are used mainly in patients with unstable angina or
acute heart attack (myocardial infarction).
What is dipyridamole?
Dipyridamole (Persantine IV,
Persantine) is another medication that decreases platelet aggregation,
though the exact mechanism of its antiplatelet action is not well understood.
Dipyridamole is not commonly used in heart attack prevention, although it is
sometimes used with aspirin to lessen the chance of stroke.
When is aspirin used for preventing and treating heart attacks and strokes?
Aspirin is widely used either alone or in combination with other antiplatelet
agents to prevent blood clots from forming in arteries. Aspirin is used
specifically in several situations including:
Aspirin often is prescribed in moderate doses (160-325 mg/day) for
patients who are having heart attacks to limit the extent of damage to the
heart's muscle (by preventing blood clot formation in the blood vessels of the
heart), prevent additional heart attacks, and improve survival.
Aspirin often is prescribed to patients undergoing
surgery to open or bypass blocked arteries, including percutaneous transluminal
coronary angioplasty (PTCA) with or without placement of coronary stents and
coronary artery bypass surgery (CABG). Aspirin also is prescribed on a long-term basis to
prevent clotting in the stents and/or the bypassed blood vessels.
Aspirin often is prescribed in low doses (75-160 mg/day) on a long-term
basis to patients with prior heart attacks or strokes and to patients with TIAs
(transient ischemic attacks or mini-strokes) and exertional angina to prevent
heart attacks and ischemic strokes.
Aspirin may be used in low dose (75-160mg/day) for
prevention of heart attack or stroke in patients with risk factors of these
conditions including longstanding diabetes,
vascular disease (previous heart
attack or stroke, or poor circulation to the legs), or angina.
Aspirin is prescribed in moderate doses (160-325 mg/day) to patients who
are having unstable angina to prevent heart attacks and improve survival.
Aspirin is prescribed in moderate doses (160-325 mg/day) to selected
patients who are having ischemic strokes to limit damage to the brain, prevent a
second stroke, and improve survival.
The knee joint is composed of three compartments and ligaments which stabilize the joint. Causes of knee pain may include injury, degeneration, infrequently infection and rarely bone tumors. Although routine x-rays do not revel meniscus tears, they can be used to exclude other problems of the bones and tissues. The knee joint is the most commonly involved joint in rheumatic disease, as well as immune diseases that affect various tissues of the body.
A stroke results from impaired oxygen delivery to brain cells via the bloodstream. A stroke is also referred to as a CVA, or cerebrovascular incident. Symptoms of stroke include: sudden numbness or weakness of the face, arm or leg. Sudden confusion, trouble speaking or understanding. Sudden trouble seeing in one or both eyes, sudden trouble walking, dizziness, or loss of balance, and/or sudden severe headache with no known cause. A TIA, or transient ischemic attack is a short-lived temporary impairment of the brain caused by loss of blood supply. Stroke is a medical emergency.
Systemic lupus erythematosus is a condition characterized by chronic inflammation of body tissues caused by autoimmune disease. Lupus can cause disease of the skin, heart, lungs, kidneys, joints, and nervous
system. When only the skin is involved, the condition is called discoid lupus.
When internal organs are involved, the condition is called systemic lupus
erythematosus (SLE).
Angina is chest pain that is due to an inadequate supply of oxygen to the heart muscle.
Angina can be caused by coronary artery disease or spasm of the coronary
arteries. EKG, exercise treadmill, stress echocardiography, stress thallium, and cardiac
catheterization are important tests used in the diagnosis of angina.
Heart attack happens when a blood clot completely obstructs a coronary
artery supplying blood to the heart muscle. A heart attack can cause chest pain, heart failure, and electrical
instability of the heart.
Chest pain is a common complaint by a patient in the ER. Causes of chest pain include broken or bruised ribs, pleurisy, pneumothorax, shingles, pneumonia, pulmonary embolism, angina, heart attack, costochondritis, pericarditis, aorta or aortic dissection, and reflux esophagitis. Diagnosis and treatment of chest pain depends upon the cause and clinical presentation of the patient's chest pain.
Ankylosing spondylitis is a type of arthritis that causes chronic inflammation of the spine. The tendency to develop ankylosing spondylitis is genetically inherited.
Psoriatic arthritis is a disease that causes skin and joint inflammation. Symptoms include painful, stiff, and swollen joints, tendinitis, and organ inflammation. Treatment involves antiinflammatory medications and exercise.
Polycythemia (elevated red blood cell count) causes are either primary (aquired or genetic mutations) or secondary (diseases, conditions, high altitude). Treatment of polycythemia depends on the cause.
Heart disease (coronary artery disease) is caused by a buildup of cholesterol deposits in the coronary arteries. Risk factors for heart disease include smoking, high blood pressure, heredity, diabetes, peripheral artery disease, and obesity. Symptoms include chest pain and shortness of breath. There are a variety of tests used to diagnose coronary artery disease. Treatment includes life-style changes, medications, procedures, or surgery.
Peripheral vascular disease (PVD) refers to diseases of the blood vessels (arteries and veins) located outside the heart and brain. While there are many causes of peripheral vascular disease, doctors commonly use the term peripheral vascular disease to refer to peripheral artery disease (peripheral arterial disease, PAD), a condition that develops when the arteries that supply blood to the internal organs, arms, and legs become completely or partially blocked as a result of atherosclerosis. Peripheral artery disease symptoms include: intermittent claudication, rest pain, numbness in the extremities, and more. Treatment for peripheral artery disease include: lifestyle measures, medication, angioplasty, and surgery.
Sickle cell anemia (sickle cell disease), a blood disease which shortens life expectancy, is cause by an inherited abnormal hemoglobin. Symptoms may include bacterial infections, painful swelling of the hands and feet, fever, leg ulcers, fatigue, anemia, eye damage, and lung and heart injury. Treatment for sickle cell anemia aims to manage and prevent the worst manifestations of the disease and focuses on therapies that block red blood cells from stacking together, which can lead to tissue and organ damage and pain.
When a portion of the brain loses blood supply, through a blood clot or embolus, a transient ischemic attack (TIA, mini-stroke) may occur. If the symptoms do not resolve, a stroke most likely has occurred. Symptoms of TIA include: confusion, weakness, lethargy, and loss of function to one side of the body. Risk factors for TIA include vascular disease, smoking, high blood pressure, high cholesterol, and diabetes. Treatment depends upon the severity of the TIA, and whether it resolves.
Kawasaki disease is a rare children's disease characterized by a fever that lasts more than five days and at least four of the following five symptoms are present: rash, swollen neck lymph gland, red tongue, swelling or redness of the hands or feet, and conjunctivitis. High doses of aspirin are used to treat Kawasaki disease. Cortisone and antiinflammatory drugs may also be used during treatment.
Chronic pain is pain (an unpleasant sense of discomfort) that persists or progresses over a long period of time. In contrast to acute pain that arises suddenly in response to a specific injury and is usually treatable, chronic pain persists over time and is often resistant to medical treatments.
Reactive arthritis is a chronic, systemic rheumatic disease characterized by three conditions, including conjunctivitis, joint inflammation, and genital, urinary or gastrointestinal system inflammation. Inflammation leads to pain, swelling, warmth, redness, and stiffness of the affected joints. Non-joint areas may experience irritation and pain. Treatment for reactive arthritis depends on which area of the body is affected. Joint inflammation is treated with antiinflammatory medications.
Vascular disease includes any condition that affects your circulatory system. Vascular disease ranges from diseases of your arteries, veins and lymph vessels to blood disorders that affect circulation.
Heart disease, particularly coronary artery disease is the leading cause of heart attacks. Women are more likely to die from a heart attack than men. High cholesterol, high blood pressure, obesity, and high triglycerides are contributors to heart disease. Some of the common symptoms of a heart attack in women include chest pain, shortness of breath, nausea, feeling faint or woozy, and more. Heart disease can be prevented by lifestyle changes and controlling high blood pressure, cholesterol, weight, and diseases such as diabetes.
Reye's syndrome (RS, or Reye syndrome) is a sudden, sometimes fatal, disease of the brain with degeneration of the liver. Reye syndrome occurs in children and comes after the chickenpox or an influenza-type illness, is also associated with taking medications containing aspirin. Symptoms include vomiting, listlessness, irritability or combativeness, confusion, delirium, delusions, convulsions, and loss of consciousness. Treatment depends on early diagnosis and focuses on protecting the brain against irreversible damage by reducing brain swelling, reversing the metabolic injury, preventing complications in the lungs, and anticipating cardiac arrest.
Nonsteroidal antiinflammatory drugs (NSAIDs) are prescribed medications for the treatment of inflammatory conditions. Examples of NSAIDs include aspirin, ibuprofen, naproxen, and more. One common side effect of NSAIDs is peptic ulcer (ulcers of the esophagus, stomach, or duodenum). Side effects, drug interactions, warnings and precautions, and patient safety information should be reviewed prior to taking NSAIDs.
Heart attacks are the major causes of unexpected, sudden death among men and women. A heart attack is also a significant cause of heart failure. Learn the risk factors for heart attack such as high blood pressure, diabetes, and other heart conditions. Lowering your risk factor, lifestyle changes, and in some cases medication are the most effective way of preventing a heart attack.
SAPHO syndrome is a chronic disorder that involves the skin, bone, and joints. SAPHO syndrome is an eponym for the combination of synovitis, acne, pustulosis, hyperostosis, and osteitis. SAPHO syndrome is related to arthritic conditions such as ankylosing spondylitis and reactive arthritis. Treatment is directed toward the individual symptoms that are present, and includes medications such as nonsteroidal antiinflammatory drugs (NSAIDs), and cortisone medications.
Eosinophilic fasciitis is a skin disease that causes thickening and inflammation of the skin and fascia. Symptoms include redness, warmth, and hardening of the skin, as well as occasional tissue and joint pain. Treatment for eosinophilic fasciitis aims to eliminate inflammation through the use of aspirin, NSAIDs, and cortisone. Aggressive forms of eosinophilic fasciitis may require the use of immune suppression medications.
A heart attack is a layperson's term for a sudden blockage of a coronary artery. This photo essay inlcudes graphics, pictures, and illustrations of diseased heart tissue and the mechanisms that lead to coronary artery disease, and possible heart attack.
Stroke is the third leading killer in the United States. Some of the warning signs of stroke include sudden confusion, trouble seeing with one or both eyes, dizziness, loss of balance, and more. Stroke prevention and reatable risk factors for stroke include lowering high blood pressure, quit smoking, heart disease, diabetes control and prevention.
Guinea worm disease (GWD or dracunculiasis) is an infection caused by the parasite Dracunculus medinensis. After a person drinks water contaminated by water fleas that harbor Guinea worm larvae, the larvae grow into adult worms (2-3 feet) in the small intestine and then migrate and emerge from the skin. Symptoms and signs include fever, swelling, and pain near the blister on the skin where the worm will emerge. As there is no medication to treat GWD and no vaccine to prevent infection, treatment focuses on minimizing pain and swelling (with the use of ibuprofen or aspirin) as the worms are slowly pulled from the wound over the course of a few days to a few months.
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