Thrombosis and thrombus

ANATOMY OR SYSTEM AFFECTED: Blood, blood vessels, brain, circulatory system, head, heart, lungs, respiratory system

DEFINITION: Thrombosis is an abnormal blood condition in which blood cells called thrombocytes (platelets) produce clots that move through the bloodstream and eventually clog blood vessels; a thrombus is such a clot.

CAUSES: Heart attacks, strokes, blood-clotting abnormalities, compromised immune system, bone marrow abnormalities, phlebitis (from surgery or prolonged confinement)

SYMPTOMS: Sudden pain or tenderness along course of vein, skin discoloration, swelling and edema below obstruction, rapid pulse, mild fever

DURATION: Acute

TREATMENTS: Anticoagulants, compression stockings

Causes and Symptoms

Clotting is a critical process in the maintenance of damaged bodily tissue and the prevention of blood loss leading to conditions of shock within the organism. Shock involves the disorientation and collapse of major organ systems within the body when excessive blood has been lost; it can be fatal if it is not treated immediately.

When the body is damaged from a cut or other breach of the body’s epithelial and defense layers in the skin, chemical signals called chemoattractants stimulate a white blood cell type called a thrombocyte to secrete proteins, leading to the sealing of the damaged tissue region. Thrombocytes, also called platelets, are versatile cells floating in the approximately 10 to 12 liters of blood flowing through roughly 100,000 kilometers of blood vessels within the average human body. There are roughly 500,000 per cubic millimeter of blood. Their clotting response to tissue damage is rapid and efficient, although very intricate in the chemical signaling between cells.

Once activated by alarmones, emergency chemical-signaling hormones released from the damaged tissue, the thrombocytes are activated to respond at the site of tissue damage. Each thrombocyte releases the proteins and fibrinogen. The thrombin modifies the to produce fibrin, the principal sealant protein for the damaged region. The is secreted massively from thousands of thrombocytes within only a few minutes of the initial tissue damage. Fibrin protein is put down by the cells in intricately connected layers from the outer edges of the tissue damage progressively inward, eventually forming a plug.

Following the sealing of the damaged tissue by the clotting thrombocytes, other of the immune system, called leukocytes, move into the region to immobilize and destroy contaminating and viruses, as well as to break down damaged cells. Surrounding healthy cells initiate mitotic cell divisions to grow into the damaged region, thereby regenerating the missing tissue. White blood cells such as leukocytes and thrombocytes are termed “white” because they do not produce and hence are not “red.” The two white blood cell types work intricately in the maintenance of body tissue primary defense layers.

When the clotting process of thrombocytes and other related cells does not occur properly, problems can arise. Normally, a will form at a breach in a blood vessel, whether that vessel is an artery carrying blood away from the heart to the body or a vein returning blood to the heart from the body. Abnormal clotting of thrombocytes and fibrin proteins, however, can form masses that break off from a blood clot and float through the bloodstream. Such a floating blood clot is called a thrombus.

A is a type of embolism, an object that floats through the bloodstream and can cause a blockage in small arteries, veins, and capillaries. Emboli can be pockets of air or solid clots such as thrombi. Both air emboli and thrombus emboli can cause serious blockages of important vessels supplying blood to particular body regions. As a thrombus or other flows along with blood, it will eventually float through a vessel that becomes progressively smaller in diameter. The thrombus blocks the vessel so that nothing can pass any farther through it—not the thrombus, not blood, and not the oxygen and within the blood.

As a result, cells downstream from the blockage will be starved for essential oxygen, sugar, and other nutrients necessary for carrying out the cellular chemical reactions of life. Most cells have only about a ten-minute supply of chemical and oxygen reserves needed for life. These cells depend on a continuous supply of blood to provide oxygen, sugar, and other nutrients and to carry away and other waste products. The blood clot occludes the artery going to a cell region, thereby preventing blood flow and causing the death of these cells. In many parts of the body, these dead cells cannot be replaced, particularly within the heart, brain, and spinal cord.

The existence of thrombi within the circulatory system is a serious medical condition known as thrombosis. The five principal types of thrombi are agonal, ball, hyaline, laminated, and white thrombi. An agonal thrombus is a type of blood clot that forms from clumping blood cells when a person is dying. A ball thrombus is a spherically shaped blood clot composed of platelets, red blood cells, and fibrin. A hyaline thrombus is a mass of depigmented, hemoglobinless, clumped red blood cells. A laminated thrombus is an array of clumped cell types accumulated at differing times, creating a snowball effect. A white thrombus is a clump of leukocytes of varying types. Regardless of type, all thrombi can seriously impede efficient blood flow and thereby contribute to localized cellular and tissue death, damage that is often irreparable.

Two of the most serious cases of localized cellular and tissue death brought about by thrombi are myocardial infarctions and strokes. A myocardial infarction, also called a heart attack, occurs when the muscular layer of cells within the heart (the myocardium) is starved for oxygen and nutrients, and dies, because of a blockage to one of the branches of the coronary supplying blood to the heart. If only a small branch of the coronary artery is blocked by a thrombus or other occlusion, then only a few hundred myocardial cells will die and the will be mild.

If the thrombus blockage is to a major coronary artery, however, then many thousands of cells in the will die, and a major heart attack will occur. It should be emphasized that the death of myocardial cells is permanent; they cannot be replaced. Therefore, a thrombus-induced heart attack causes permanent death of a region of heart muscle, whether large or small. In many cases, the heart attack is so severe that the normal, rhythmic contraction of the heart is disrupted, thereby leading to and death.

In the same manner, a stroke, also called a cerebrovascular accident, occurs when an artery transporting blood to a region of cells is blocked by a thrombus or other embolus. Brain cells downstream from the blockage are starved for oxygen and nutrients; they die within minutes. If a small artery or capillary is blocked, only a few brain cells will die and the will be minimal, perhaps not even noticeable to the individual. It is possible that many people have such “microstrokes” repeatedly during the course of their lives, although the effects of these small strokes are cumulative over time. Decreased and impaired neurological and motor functioning throughout the body ensue from damaged brain regions in stroke victims.

If the thrombus-induced blockage is to an artery supplying blood to a large brain cell region, however, then millions of brain cells will die. The stroke is severe, perhaps deadly, if the affected brain region is essential for certain bodily life processes. If the severe stroke victim survives, then the effects will be noticeable as sluggish neuromuscular motor activity on the opposite side of the body from the affected brain region. Heart attacks and strokes are manifestations of the same problem: arteries occluded by thrombi and other emboli.

Treatment and Therapy

Thrombosis is a problem of major concern for the physician facing patients with certain types of medical conditions and patients who recently have had major internal surgery. Furthermore, individuals with blood-clotting abnormalities, compromised immune systems, and abnormalities also are prone to forming thrombi and other solid emboli. Phlebitis is an of a vein brought about by surgery, prolonged confinement to bed, or prolonged sitting, in which blood clots form in deep veins, a condition called (DVT). These blood clots can break off and flow through the general blood circulation, eventually clogging an artery or vein leading to a critical bodily region.

Consequently, thrombi and are of major concern to medical doctors because they represent potential complications and side effects from other medical conditions and certain needed surgical treatments. People who have had abdominal or pelvic surgery (such as the removal of certain organs such as the and portions of the stomach because of cancer) or individuals who have been bedridden with leg fractures are prone to forming thrombi and emboli.

The elderly are particularly prone to thrombi because of the gradual decline of the and the breakdown of bone development that accompany the process. Moreover, the natural chemical substances in the blood that dissolve floating blood clots are not as prevalent in the elderly. As a result, more cases of thrombi are seen in elderly patients, particularly individuals above the age of seventy.

Once thrombi and other solid emboli have formed, they may float for a long time through an individual’s blood vessels. They usually can pass through the heart unimpeded without causing any serious disruptions of cardiac rhythm. Occasionally, large thrombi can become lodged in one of the four of the heart, creating an and triggering a heart attack, but this is very rare. More commonly, the thrombi become trapped in the general in progressively smaller arteries and going to a localized tissue region.

Within the body, oxygenated blood leaves the left ventricle of the heart through the largest artery in the body, the aorta, and subsequently branches and subbranches through thousands of successively smaller arteries, arterioles, and capillaries until reaching each of the quadrillion cells of the body. These cells extract oxygen and nutrients from the blood and deposit carbon dioxide and waste products into the bloodstream. Small capillaries combine to produce small venules that combine to produce small veins, which in turn combine into larger veins. These eventually come together into the inferior and vena cavae, returning blood to the right atrium of the heart for eventual delivery to the lungs. Once in the heart, blood flows from the right atrium to the right ventricle and then through the arteries branching to the tissues of the lungs, where the blood is oxygenated through breathing. Oxygenated blood returns to the left atrium of the heart via the pulmonary veins and then flows through the left ventricle to the to make another trip through the body.

Thrombi can flow through this system repeatedly. They usually become caught, however, in the progressively smaller arteries and capillaries transporting blood to the tissues. The resulting blockage and starvation of cells downstream from the blockage leads to the death and decay of the affected tissue region, resulting in a localized tissue infarction. The two most serious types of infarctions are the myocardial and the stroke, but both of these infarctions can be caused by other types of blockages, including arterial rupture and fatty clogging of arteries from the conditions and arteriosclerosis. Nevertheless, thrombi are a major contributory factor to the occurrences of strokes and heart attacks, two leading killers in the United States and other stressful, technological Western nations. In both strokes and heart attacks, thrombal blockages to key cellular regions lead to localized cellular death. Heart cells and brain cells cannot be regenerated. The tissue death is permanent, and the resulting effects will remain with the victims for the rest of their lives if they survive the stroke or heart attack.

Another serious thrombal blockage can occur in the pulmonary arteries and arterioles transporting blood to lung tissue for oxygenation. Such blockages lead to the localized death of lung tissue and sudden shortness of breath in affected individuals. About 10 percent of cases of pulmonary thrombosis and end in death, resulting in a fatality figure much smaller than the hundreds of thousands of deaths from heart attacks and strokes in the United States each year.

Scuba divers who spend excessive periods of time at great depths and then ascend rapidly are prone to decompression sickness, or “the bends,” in which nitrogen bubbles form emboli that create the same blockages as thrombi in localized tissue spaces. Nitrogen bubble emboli can accumulate in the heart, lung, and brain tissue and are fatal if not immediately treated in a decompression chamber.

Perspective and Prospects

Thrombi and thrombosis are serious problems that can arise in any individual, although the likelihood increases with age and the corresponding decline in individuals’ immune systems. Care must be taken with various surgical procedures, particularly abdominal and pelvic surgery and the treatment of leg fractures, to reduce the chances of thrombi forming. Any severe cut has the potential to form thrombi, but the status of an individual’s immune system is an important factor in determining whether these thrombi are captured and dissipated.

In many surgical procedures, including open heart surgery, physicians and surgeons will administer anticlotting agents to minimize the risk of thrombi forming during and following the surgery and in the recovery phase of the operation. These anticlotting agents are administered intravenously and diffuse throughout the patient’s circulatory system so that any thrombi and other blood clots dissolve before they can occlude various tissue regions. Medical doctors are versed in the science of thrombi and thrombosis because these conditions often are associated with other medical conditions. Physicians are aware of contributory factors to thrombosis and can take action to guard against thrombal occurrence early in the medical treatment process.

Since the 1950s, the drug warfarin has been given to patients for a period of three to six months. Studies showed an increased risk of severe bleeding with longer use of warfarin, thus preempting its use after six months. However, without warfarin, nearly one-third of patients will form another blood clot within eight years. In 2003, findings showed that after several months of full doses of warfarin, moderate doses of the medicine can follow and can reduce the risk of further clots without introducing the risk of hemorrhage. A study published in the International Journal of Cardiology in May 2013 reported that the drug Pradaxa (dabigatran) was comparably effective against stroke. In the 2020s, doctors also prescribed other anticoagulants that can reduce the risk of blood clots with less bleeding. These include Eliquis (apixaban), Lixiana or Savaysa (edoxaban), and Xarelto (rivaroxaban).

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