Effects on blood coagulation, fibrinolysis, and platelet aggregation of normal and atheromatous aortic tissue

1. C. R. M. Prentice,
2. G. P. McNicol,
3. A. S. Douglas

1. University Department of Medicine, Glasgow Royal Infirmary

Abstract

A comparison was made between the effects of atheromatous and normal areas of the same aorta on coagulation,
fibrinolytic, and platelet aggregating systems.

In the thromboplastin generation test it was found that atheromatous aorta possessed significantly greater ability to
generate intrinsic prothrombin activator than did normal aortic tissue. But, by the one-stage prothrombin time
technique, the content of extrinsic thromboplastin in both types of aorta was similar.

Aortic preparations, consisting of intimal and medial layers only, were not found to possess fibrinolytic ability and
did not contain inhibitors of the fibrinolytic system.

The adhesion of platelets to ulcerated atheromatous areas of aorta was significantly greater than to normal or non-
ulcerated atheromatous areas. However, homogenates of atheromatous and normal aorta did not differ in their
ability to accelerate platelet aggregation and fibrin clot formation when tested by a modified Chandler's tube
technique.

The significance of the findings is discussed and the suggestion made that the mechanisms by which atheromatous
aortic tissue might predispose towards intravascular thrombosis in vivo are the ability of such tissue to enhance
intrinsic prothrombin activator formation and platelet aggregation.

Atherosclerosis 

Definition
Atherosclerosis is the build up of a waxy plaque on the inside of blood vessels. In Greek, athere means gruel, and
skleros means hard. Atherosclerosis is often called arteriosclerosis. Arteriosclerosis (from the Greek arteria,
meaning artery) is a general term for hardening of the arteries. Arteriosclerosis can occur in several forms,
including atherosclerosis.

Description
Atherosclerosis, a progressive process responsible for most heart disease, is a type of arteriosclerosis or
hardening of the arteries. An artery is made up of several layers: an inner lining called the endothelium, an elastic
membrane that allows the artery to expand and contract, a layer of smooth muscle, and a layer of connective
tissue. Arteriosclerosis is a broad term that includes a hardening of the inner and middle layers of the artery. It
can be caused by normal aging, by high blood pressure, and by diseases such as diabetes. Atherosclerosis is a
type of arteriosclerosis that affects only the inner lining of an artery. It is characterized by plaque deposits that
block the flow of blood.

Plaque is made of fatty substances, cholesterol, waste products from the cells, calcium, and fibrin, a stringy
material that helps clot blood. The plaque formation process stimulates the cells of the artery wall to produce
substances that accumulate in the inner layer. Fat builds up within these cells and around them, and they form
connective tissue and calcium. The inner layer of the artery wall thickens, the artery's diameter is reduced, and
blood flow and oxygen delivery are decreased. Plaques can rupture or crack open, causing the sudden formation
of a blood clot (thrombosis). Atherosclerosis can cause a heart attack if it completely blocks the blood flow in the
heart (coronary) arteries. It can cause a stroke if it completely blocks the brain (carotid) arteries. Atherosclerosis
can also occur in the arteries of the neck, kidneys, thighs, and arms, causing kidney failure or gangrene and
amputation.
Causes and symptoms
Atherosclerosis can begin in the late teens, but it usually takes decades to cause symptoms. Some people
experience rapidly progressing atherosclerosis during their thirties, others during their fifties or sixties.
Atherosclerosis is complex. Its exact cause is still unknown. It is thought that atherosclerosis is caused by a
response to damage to the endothelium from high cholesterol, high blood pressure, and cigarette smoking. A
person who has all three of these risk factors is eight times more likely to develop atherosclerosis than is a person
who has none. Physical inactivity, diabetes, and obesity are also risk factors for atherosclerosis. High levels of the
amino acid homocysteine and abnormal levels of protein-coated fats called lipoproteins also raise the risk of
coronary artery disease. These substances are the targets of much current research. The role of triglycerides,
another fat that circulates in the blood, in forming atherosclerotic plaques is unclear. High levels of triglycerides
are often associated with diabetes, obesity, and low levels of high-density lipoproteins (HDL cholesterol). The
more HDL ("good") cholesterol, in the blood, the less likely is coronary artery disease. These risk factors are all
modifiable. Non-modifiable risk factors are heredity, sex, and age.

Risk factors that can be changed:

 Cigarette/tobacco smoke-Smoking increases both the chance of developing atherosclerosis and the
chance of dying from coronary heart disease. Second hand smoke may also increase risk.
 High blood cholesterol-Cholesterol, a soft, waxy substance, comes from foods such as meat, eggs, and
other animal products and is produced in the liver. Age, sex, heredity, and diet affect cholesterol. Total
blood cholesterol is considered high at levels above 240 mg/dL and borderline at 200-239 mg/dL. High-
risk levels of low-density lipoprotein (LDL cholesterol) begin at 130-159 mg/dL.
 High triglycerides-Most fat in food and in the body takes the form of triglycerides. Blood triglyceride levels
above 400 mg/dL have been linked to coronary artery disease in some people. Triglycerides, however, are
not nearly as harmful as LDL cholesterol.
 High blood pressure-Blood pressure of 140 over 90 or higher makes the heart work harder, and over time,
both weakens the heart and harms the arteries.
 Physical inactivity-Lack of exercise increases the risk of atherosclerosis.
 Diabetes mellitus-The risk of developing atherosclerosis is seriously increased for diabetics and can be
lowered by keeping diabetes under control. Most diabetics die from heart attacks caused by
atherosclerosis.
 Obesity-Excess weight increases the strain on the heart and increases the risk of developing
atherosclerosis even if no other risk factors are present.

Risk factors that cannot be changed:

 Heredity-People whose parents have coronary artery disease, atherosclerosis, or stroke at an early

The progression of atherosclerosis.

age are at increased risk. The high rate of severe hypertension among African-Americans puts them at
increased risk.

 Sex-Before age 60, men are more likely to have heart attacks than women are. After age 60, the risk is
equal among men and women.
 Age-Risk is higher in men who are 45 years of age and older and women who are 55 years of age and
older.

Symptoms differ depending upon the location of the atherosclerosis.

 In the coronary (heart) arteries: Chest pain, heart attack, or sudden death.
 In the carotid (brain) arteries: Sudden dizziness, weakness, loss of speech, or blindness.
 In the femoral (leg) arteries: Disease of the blood vessels in the outer parts of the body (peripheral
vascular disease) causes cramping and fatigue in the calves when walking.
 In the renal (kidney) arteries: High blood pressure that is difficult to treat.
Diagnosis
Physicians may be able to make a diagnosis of atherosclerosis during a physical exam by means of a stethoscope
and gentle probing of the arteries with the hand (palpation). More definite tests are electrocardiography,
echocardiography or ultrasonography of the arteries (for example, the carotids), radionuclide scans, and
angiography.

An electrocardiogram shows the heart's activity. Electrodes covered with conducting jelly are placed on the
patient's body. They send impulses of the heart to a recorder. The test takes about 10 minutes and is performed
in a physician's office. Exercise electrocardiography (stress test) is conducted while the patient exercises on a
treadmill or a stationary bike. It is performed in a physician's office or an exercise laboratory and takes 15-30
minutes.

Echocardiography, cardiac ultrasound, uses sound waves to create an image of the heart's chambers and valves.
A technician applies gel to a hand-held transducer, presses it against the patient's chest, and images are
displayed on a monitor. This technique cannot evaluate the coronary arteries directly. They are too small and are
in motion with the heart. Severe coronary artery disease, however, may cause abnormal heart motion that is
detected by echocardiography. Performed in a cardiology outpatient diagnostic laboratory, the test takes 30-60
minutes. Ultrasonography is also used to assess arteries of the neck and thighs.

Radionuclide angiography and thallium (or sestamibi) scanning enable physicians to see the blood flow through
the coronary arteries and the heart chambers. Radioactive material is injected into the bloodstream. A device
that uses gamma rays to produce an image of the radioactive material (gamma camera) records pictures of the
heart. Radionuclide angiography is usually performed in a hospital's nuclear medicine department and takes 30-
60 minutes. Thallium scanning is usually done after an exercise stress test or after injection of a vasodilator, a
drug to enlarge the blood vessels, like dipyridamole (Persantine). Thallium is injected, and the scan is done then
and again four hours (and possibly 24 hours) later. Thallium scanning is usually performed in a hospital's nuclear
medicine department. Each scan takes 30-60 minutes.

Coronary angiography is the most accurate diagnostic method and the only one that requires entering the body
(invasive procedure). A cardiologist inserts a catheter equipped with a viewing device into a blood vessel in the
leg or arm and guides it into the heart. The patient has been given a contrast dye that makes the heart visible to x
rays. Motion pictures are taken of the contrast dye flowing though the arteries. Plaques and blockages, if present,
are well defined. The patient is awake but has been given a sedative. Coronary angiography is performed in a
cardiac catheterization laboratory and takes from 30 minutes to two hours.

Treatment
Treatment includes lifestyle changes, lipid-lowering drugs, percutaneous transluminal coronary angioplasty, and
coronary artery bypass surgery. Atherosclerosis requires lifelong care.

Patients who have less severe atherosclerosis may achieve adequate control through lifestyle changes and drug
therapy. Many of the lifestyle changes that prevent disease progression-a low-fat, low-cholesterol diet, losing
weight (if necessary), exercise, controlling blood pressure, and not smoking-also help prevent the disease.