Blood clots

Definition

A blood clot is a mass of blood cells and blood components that form to stop the bleeding that occurs when a blood vessel is injured. When a blood vessel is broken, platelets in the blood become sticky and clump together at the site of the injury. They begin to form a mass to stop the flow of blood.

Description

Clotting is the body's normal response to a bleeding injury. It is a necessary function to prevent a person from losing too much blood. Most blood clots dissolve back into the blood when the body has healed the vessel. Blood clots, however, can be potentially dangerous if they occur within healthy blood vessels, or if they do not dissolve when their work is done. A thrombus is a blood clot that forms along the wall of the heart or a blood vessel. This type of clot can slow blood flow, and if the clot becomes large enough, it may stop the flow of blood in the vessel. An embolus is a clot that forms in one area of the body, travels through the bloodstream, and lodges in another vessel in the body. Emboli are less common and more dangerous, because they can cause a sudden blockage in blood flow (embolism), which could be fatal. An embolism occurring in an artery will block blood flow to an organ or tissue, and could cause tissue damage or death. An embolism in:

• a cerebral (brain) artery can cause a stroke
• a coronary artery can cause a heart attack
• a pulmonary (lung) artery can cause shortness of breath or death
• a retinal artery can cause sudden blindness in one eye
• an artery supplying blood to a limb can cause tissue damage and possibly gangrene
• any artery leading to an organ can cause loss of that organ's function

Causes & symptoms

There are several factors that contribute to the formation of blood clots. Phlebitis is a condition that may increase abnormal blood clot formation. Blood diseases or other conditions—especially inflammation—that alter the quality of the blood can also affect clot formation. Plaque formation in the arteries (atherosclerosis ) and damaged blood vessels both increase the chance of blood clots because they slow blood flow and provide a place for platelets to collect and form a clot. Genetic factors also play a role in tendency to form blood clots. Diet can have an effect on clot formation, as well. Cholesterol and saturated fats, which are also implicated in atherosclerosis, can contribute to clot formation. People whose diets are low in essential fatty acids , vegetables, and fish, and who do not take in proper amounts of nutrients and antioxidants are also at a higher risk for clots. Conditions or body positions that slow blood circulation—extended bed rest or sitting in a car or airplane for long periods of time—may also cause blood clots to form; although one recent British study suggests that the risk of so-called "traveler's thrombosis" is not as great as has been thought. Blood clots can be caused by increased fibrinogen (a blood-clotting factor) due to estrogen in the late stages of pregnancy and from long-term use of birth control pills. Other factors include varicose veins, childbirth, sickle cell anemia, smoking, obesity , liver disease, and cardiovascular disorders.

There may be no obvious symptoms of a blood clot. When symptoms do occur, they often appear suddenly, and point to the location of the clot. Extreme dizziness that occurs without warning can indicate a clot in a cerebral artery. Sudden complete or partial blindness in one eye could indicate a clot within the retinal artery. A hard blue bulge in a vein, or unexpected pain in an arm or leg, along with numbness, weakness, or another sign that blood is not reaching the area, could indicate a blood clot. Blisters or ulcers on the skin may occur as well. A clot in an artery near a major organ like the heart or lung will produce pain or decreased activity in that organ. Gangrene (death of tissue) may occur if blood flow to a region is blocked for an extended period of time.

Diagnosis

The patient will describe the severity and location of the pain he or she has been experiencing. A physician may also notice such physical signs of a blood clot as the swelling blue bulge, discoloration of a limb, or an ulcer. Medical personnel will also check for a missing or lowered pulse or blood pressure in a limb. A Doppler ultra-sound examination, angiography, or arteriography may be used to detect the location of the clot.

Treatment

Nutritional therapy may include the following: vitamins B₃ (niacin ), B₆, C, and E; fatty acid and garlic supplements; and the minerals zinc, magnesium , and manganese . Herbal remedies may include cayenne (Capsicum frutescens ), other hot peppers, and gingko (Ginkgo biloba ) to help reduce the protein fibrin, which is a necessary factor in blood clots. Bilberry (Vaccinium myrtillus ), turmeric (Curcuma longa ), and ginger (Zingiber officinale ) help reduce platelets' stickiness, which is essential for clot formation. Onion (Allium sepa ) and garlic (A. sativum ) help reduce fibrin and platelet stickiness. Patients who are taking prescribed anticoagulant drugs should consult their doctors before starting vitamin, nutritional, or herbal therapies.

Hydrotherapy treatment for blood clots can include contrast applications. The patient alternates using hot and cold treatments on the body in the area of the clot to increase blood flow. A naturopath will recommend specific remedies based on the symptoms and personality of a particular patient. A remedy for blood clots may include Hamamelis. Massage can be helpful if blood clots are a result of poor circulation, although care should be taken if a person suffers from phlebitis, since a clot could mobilize and lodge elsewhere.

Allopathic treatment

Anticoagulant (anticlotting) drugs are usually prescribed for patients with blood clots. Streptokinase is a drug that will help dissolve clots that are already present in the body. Heparin inhibits platelet clumping, and can be prescribed after surgery, when blood is likely to clot. A new and promising treatment to prevent clot formation associated with septic shock is a recombinant form of activated human protein C, a natural anticoagulant. Doctors may prescribe aspirin for people who are at risk for having blood clots, although aspirin can injure the stomach lining. Patients may want to ask their doctors about what can be done to minimize damage from aspirin. Surgery is only recommended to remove blood clots that appear to be life-threatening or will cause tissue death if not removed.

Expected results

If a clot goes undetected it is potentially dangerous, and could lead to a stroke, heart attack, or other serious complication. It is important to have any sudden unexplained pain or loss of function checked out by a doctor. If the blood flow to a limb is blocked for an extended period of time, gangrene may set in, and the limb may require amputation. Diet and exercise can help prevent future clots.

Prevention

Some risk factors, such as genetically related diseases, cannot be minimized. But minimizing other risk factors will help prevent problems with blood clots. Quitting smoking, controlling obesity, and improving nutrition can help reduce the risk of problematic blood clotting.

A healthy diet with high-fiber, low-cholesterol foods and plenty of fruits and vegetables can help prevent blood clots and many of the conditions that can lead to blood clots, such as atherosclerosis. In addition, such foods as garlic, ginger, onions, and hot peppers can help reduce platelet stickiness and formation of clots. Fish oils and supplements that add nutrients to the diet are recommended as well.

Moderate exercise helps keep off extra weight and improves circulation, both of which help reduce risk factors for formation of blood clots. Exercise can also reduce the risk of blood clots in women who use birth control pills for long periods of time. Those who must sit for long periods of time—on an airplane, in a car, or at work—can help prevent blood clots by wearing loose clothing, walking, and stretching their legs whenever possible. Flexing and releasing the lower body muscles, even while sitting, can help improve circulation as well.

Resources

BOOKS

Cassileth, Barrie R. The Alternative Medicine Handbook: The Complete Reference Guide to Alternative and Complementary Therapies. New York: W.W. Norton and Company, 1998.

Somerville, Robert. The Medical Advisor: The Complete Guide to Alternative & Conventional Treatments. Alexandria, VA: Time Life Inc., 1996.

Strohecker, James. Alternative Medicine: The Definitive Guide. Tiburon, CA: Future Medicine Publishing, Inc., 1994.

PERIODICALS

Adedeji, Moses O., Julio Cespedes, et al. "Pulmonary Thrombotic Arteriopathy in Patients with Sickle Cell Disease." Archives of Pathology and Laboratory Medicine 125 (November 2001): 1436–1441.

"Better Than Aspirin?" Industry Week (July 7, 1997): 32.

Egermayer, Paul. "The 'Economy Class Syndrome': Problems With the Assessment of Risk Factors for Venous Thromboembolism." Chest 120 (October 2001): 1047–1048.

Hinds, C. J. "Treatment of Sepsis With Activated Protein C: Encouraging News for Well Selected Patients. British Medical Journal 323 (October 23, 2001): 881–882.

OTHER

Medline Plus Health Information. "Blood clots." March 1, 2001 [cited October 2002]. <http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm>.

WebMDHealth. <http://my.webmd.com>.

Heather Bienvenue

Rebecca J. Frey, PhD

Blood Clots

Definition

A blood clot is a thickened mass in the blood formed by tiny substances called platelets. Clots form to stop bleeding, such as at the site of cut. But clots should not form when blood is moving through the body; when clots form inside blood vessels or when blood has a tendency to clot too much, serious health problems can occur.

Description

As soon as a blood vessel wall is damaged—by a cut or similar trauma—a series of reactions normally takes place to activate platelets to stop the bleeding. Platelets are the tiny particles in the blood released into the bone marrow that gather together and form a barrier to further bleeding. Several proteins in the body are involved in the platelets clotting process. Chief among these proteins are collagen, thrombin, and von Willebrand factor. Collagen and thrombin help platelets stick together. As platelets gather at the site of injury, they change in shape from round to spiny, releasing proteins and other substances that help catch more platelets and clotting proteins. This enlarges the plug that becomes a blood clot. Formation of blood clots also is called "coagulation".

The series of reactions that cause proteins and platelets to create blood clots also are balanced by other reactions that stop the clotting process and dissolve clots after the blood vessel has healed. If this control system fails, minor blood vessel injuries can trigger clotting throughout the body. The tendency to clot too much is called "hypercoagulation". Anytime clots form inside blood vessels, they can lead to serious complications.

The formation of a clot in a blood vessels may be called thrombophlebitis. The term refers to swelling of one or more veins caused by a blood clot. Although some clots occur in the arms or small, surface blood vessels, most occur in the lower legs. When the blood clot occurs in a deep vein, it is called deep vein thrombosis, or DVT. As many as one of every 1,000 Americans develops DVT each year. The danger of DVT comes when pieces of the clot, known as emboli, break off and travel through the bloodstream to an artery.

A blood clot that blocks an artery to the brain can cause a stroke. If the clot blocks blood flow to the lungs pulmonary embolism can occur. A blood clot that blocks a coronary artery can cause a heart attack. Certain people are at higher risk for blood clots than others; surgery, some injuries, childbirth and lying or sitting still for extended periods of time put people at higher risk, as do inherited disorders. Once a person has a blood clot, he or she may have to take bloodthinning drugs to prevent clots from recurring. Men and women are at similar risk for blood clots. A recent study in Austria found that men run a higher risk of recurring blood clots than women, though the reason is unknown.

Causes and symptoms

Many causes can lead to blood clots, some genetic and some environmental. An environmental cause of DVT is prolonged inactivity. For instance, having to sit in a car or airplane for a long period of time decreases blood flow in the lower legs. Recent studies have shown that 1% of air travelers develop blood clots, usually on long flights of five hours or more. However, one study in 2004 found that air travelers developed clots on flights as short as three hours, though they often dissolved naturally and did not lead to complications. Other environmental causes of blood clots include use of hormone replacement therapy to ease menopausal symptoms, oral contraceptives for birth control, pregnancy (and a childbirth within the past six weeks), recent surgery or procedures involving use of a central venous access catheter, and cancer. Smoking also is an important and preventable environmental risk for blood clots.

KEY TERMS

Central venous access catheter— A tube placed just beneath the skin to allow doctors and nurses constant and pain-free access to the veins, often when a patient is in the hospital or has a chronic disease such as cancer. The doctors and nurses can draw blood and give medications and nutrients through the catheter.

Genetic— A trait or condition that is acquired or inherited because it was related to genes and DNA.

Pulmonary embolism— The sudden obstruction of a pulmonary (lung) artery or one of its branches by an abnormal particle (such as a blood clot) floating in the blood.

Some people are born with a higher risk for blood clots. Hypercoagulation disorders are genetic conditions. Usually the body doesn t produce enough of the proteins involved in the clotting process, so they cannot do their job to stop the clotting; in other cases, they have an extra protein that causes too much clotting.

There may be no symptoms of blood clots until they grow so large that they block the flow of blood through the vein. Then, symptoms may develop suddenly around the area and include:

• Pain or tenderness in the affected area.
• Warmth or redness of the skin in the affected area.
• Sudden swelling in the affected limb.

Additional symptoms may indicate serious complications of blood clots such as pulmonary embolism, stroke, and heart attack. If vein swelling or pain are accompanied by high fever or shortness of breath, rapid pulse, or chest pain, or other symptoms that may indicate stroke, heart attack, or pulmonary embolism, it is advised to go to an emergency room immediately.

Diagnosis

A physician will diagnose blood clots based on patient history and one of several diagnostic imaging exams. The patient's history will help determine possible risk factors that may lead to suspected blood clots. In addition to family history or known genetic disorders, the patient may mention an environmental factor such as recent air travel or use of high-risk mediations.

To help get a picture of suspected clots inside the veins, the first test chosen normally is an ultrasound. Doppler or duplex ultrasound uses sound waves that travel through tissue and reflect back. A computer transforms the sound waves into moving images on the screen that may show the clot, as well as blood flow near the clot and any abnormalities. Ultrasound does not use x rays and is a noninvasive method. Computed tomography (CT) scans also might be used to image the blood vessels. It is similar to x rays, except the images are much like cross-section slices with greater detail that can be computerized and even viewed three dimensionally. A special dye called a contrast agent may be injected before the exam to help highlight the veins. Magnetic resonance angiography uses magnetic resonance imaging (MRI) to image the blood vessels. It also may involve injection of a contrast dye. Venography is less commonly used, but involves injecting a contrast and using x rays to image the vein.

Treatment

Medicines can help thin blood, making it less likely to clot. The two most common blood thinners are heparin and warfarin. Heparin works right away, keeping blood clots from growing. It usually is injected. In recent years, more physicians have been prescribing low-molecular weight heparin, purified versions of the drug that can be given with less monitoring. Warfarin (coumadin) often is used for long-term treatment of blood clots and is taken orally. Patients must work closely with their physicians to constantly monitor its effects and adjust dose if necessary. Too little warfarin can lead to clotting, but too much can thin the blood so much that causing life-threatening bleeding can occur. The same can be true of low-molecular weight heparin when used on a long-term, at-home basis.

Other treatments for blood clots include injecting clot busting drugs directly into the clot through a catheter, or in rare instances, installation of a filter to block a clot from lodging in the lungs. Sometimes, surgery also is needed to remove a clot blocking a pelvic or abdominal vein or one that is chronic and disabling. A cardiovascular surgeon or interventional radiologist may perform balloon angioplasty or insert a stent to open a narrowed or damaged vein. In an emergency situation, a drug called tissue plasminogen activator, or tPA, may be given to immediately dissolve a life-threatening blood clot to the brain or heart. In 2004, the U.S. Food and Drug Administration approved a new, small, corklike device that can be used to remove blood clots from the brains of patients who cannot receive clot-busting drugs.

Alternative treatment

Garlic is thought to lower blood clotting potential. Less evidence suggests onions and cayenne pepper may help keep blood thin. New research from Australia adds tomato juice to the list of potential blood thinners. Subjects who drank a glass of tomato juice a day reduced their risk for DVT, stroke and cardiovascular disease. Research has shown that a natural soy and pine product called pinokinase has been effective in controlling DVT in air travelers. Patients seeking alternative treatments for blood clots should work with certified practitioners and should inform their allopathic provider about their alternative care.

Prognosis

If detected and controlled with medications, blood clots can be safely managed. However, if the clots become dislodged and travel to an artery, they can cause nearly instant death. For instance, more than 600,000 people have a pulmonary embolism each year and more than 10% of them die from the embolism, most of them within 30 to 60 minutes after symptoms start.

Prevention

Clots may be avoided by not smoking, and by not using medications that add to the risk. Clotting can be prevented by following physician recommendations concerning medications. Sometimes, physicians will prescribe special support stockings that prevent swelling and reduce chances of DVT. When taking an air flight of six hours or longer, drinking plenty of fluids to avoid dehydration, avoiding tight clothing around the waist, and stretching calves every hour can help prevent DVT. It is advised that those on long flights get up and move about once an hour during the flight. If not possible, moving the legs regularly while seated by flexing the ankles, then pressing the feet against the seat in the row ahead or on the floor can help stretch the calves. A physician may advise those at high risk of DVT wear support stockings during the flight or take low-molecular weight heparin two to four hours before departure.

Resources

PERIODICALS

"Air Travel, Especially Long Flights, May Increase the Risk of Blood Clots." Women's Health Weekly (Dec. 25, 2003):119.

"In-flight Exercises for a Healthy Trip: Prevent Dangerous Blood Clots With These Three Easy Moves the Next Time You Fly." Natural Health (Jan-Feb. 2003):27.

Stephenson, Joan. "FDA Orders Estrogen Safety Warnings: Agency Offers Guidance for HRT Use." JAMA, The Journal of the American Medical Association (Feb. 5, 2003):537-539.

"Study Finds One Percent of Air Travelers Develop Injurious Blood Clots." Heart Disease Weekly (Jan. 25, 2004):41.

"Tiny Corkscrew Clears Blood Clots." Hematology Week (Sept. 6, 2004):99.

ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105, Behtesda, MD 20824-0105. 301-592-8573. www.nhlbi.nih.gov.

Society of Interventional Radiology. 10201 Lee Highway, Suite 500, Fairfax, VA 22030. 703-691-1805. http://www.sirweb.org.

OTHER

Avoid Deep Vein Thrombosis: Keep the Blood Flowing. FDA Web site, 2005. www.fda.gov/fdac/features/2004/604_vein.html.

Blood clots

Definition

Blood clots are semi-solid clumps of coagulated blood. Blood clots that form in an uninjured blood vessel are not normal.

Description

Clotting of blood is a natural process in which liquid blood thickens to a jelly-like consistency. Normally, a blood clot stops the flow of blood after an injury to a blood vessel, to prevent blood loss and to allow healing to occur. As healing takes place, the blood clot gradually dissolves and is absorbed by the body. However, blood clots can occur in an abnormal way when an injury has not occurred.

A blood clot that forms in an artery is called an arterial thrombus or thrombosis. A blood clot that forms and blocks a major artery is potentially life-threatening or limb-threatening because blood flow through the artery is compromised and damage to vital organs can occur. A blood clot in a vein is called a venous thrombus or thrombosis. Blood clots are also dangerous because they may travel through the circulation and block distant blood vessels. A blood clot that leaves the site where it formed and travels through the bloodstream is called an embolus. A blood clot anywhere may or may not be life-threatening, and may cause anything from virtually no symptoms to sudden death .

Demographics

A history of mitral valve prolapse , an enlarged heart, atrial fibrillation (an irregular heartbeat), or heart failure increase risk of developing an arterial blood clot. Obesity, varicose veins , heart failure, or a sedentary lifestyle are risk factors for development of a venous blood clot. People who smoke are at an increased risk for blood clots, as are people with a family history of blood clots or blood clotting disorders.

Causes and symptoms

The clotting of blood is a complicated process that may be affected by many factors. Some factors are unknown, but blood clots are often the result of an underlying condition or lifestyle element. The following list is a sample of known causes for an increased risk of blood clots:

• Current diagnosis of cancer: Cancer interferes with normal blood circulation.
• Elevated levels of homocysteine: Homocysteine is an amino acid (building block of protein). Excess levels in the body are associated with an increased risk of arterial blood clots.
• Family or personal history of a blood clot or blood clotting disorder.
• Hormone replacement therapy.
• Long distance travel, immobility, or a sedentary lifestyle.
• Smoking.
• Advancing age.
• Obesity.
• Heart problems such as a history of stroke, heart attack, and heart disease including coronary artery disease.
• Elevated cholesterol levels.
• Hypothyroidism.
• Infection, inflammation, serious trauma, or surgery l High blood pressure.
• Autoimmune disorders such as lupus and rheumatoid arthritis.

The symptoms of a blood clot are dependent upon where the clot is located in the body. A blood clot in the lungs may cause chest pain , an accelerated heart rate, shortness of breath, dizziness or fainting , coughing up blood-tinged mucus, or a low-grade fever. In the artery of an arm or leg, a blood clot may cause pain, especially with moving the limb; difficulty moving the limb; numbness or tingling; and a pale discoloration to the affected extremity. In the vein of an arm or leg a blood clot may cause swelling, redness, tenderness, and discomfort to the affected arm or leg. Chest pain and a heart attack may ensue if a blood clot forms or travels to the heart. A blood clot in the abdomen may cause abdominal pain, vomiting, and/or diarrhea .

Diagnosis

When a blood clot is suspected, certain tests are ordered to confirm the diagnosis. These tests include ultrasound, computerized axial tomography (CAT scan), and magnetic resonance imaging (MRI). An angiogram (also known as an arteriogram) may be done if a blood clot is suspected in an artery.

Ultrasound produces images of the blood vessels and organs in the body to help assess blood flow. CAT scans and MRI provide high quality imaging of blood vessels and blood flow through the arteries. An arteriogram involves injection of a dye to evaluate the condition of the arteries and to determine if there is any blood flow obstruction.

Treatment

Treatment depends on whether the blood clot is an arterial or venous embolus or thrombus, the size of the blood clot, and the patient's general medical condition. If a blood clot has resulted in a heart attack or stroke , intravenous (IV) medication may be used to break up the clot. This treatment is followed by anticoagulant (blood-thinning) medication. Medication that interferes with the blood's ability to clot, called anti-platelets, may also be used. Aspirin is an example of an anti-platelet medication.

If anticoagulant medication is not effective, a special device called a vena cava filter may be used.

The filter is placed by a physician into the vena cava (the large vessel that transports blood from the lower extremities to the heart and lungs) to trap blood clots in the lower extremities before they reach the heart and lungs. Surgical intervention may be attempted to aspirate or remove the blood clot. Surgery may involve bypassing the area of obstruction caused by the clot in an attempt to improve blood flow or dilatation (with or without a balloon catheter called a stent) of the obstructed blood vessel.

Nutrition/Dietetic concerns

A diet low in fats and cholesterol can help reduce the risk for blot clot development. Individuals who are overweight or obese should take measures to lose weight through improved nutrition and exercise . Ginseng, a nutritional supplement, may interfere with the effects of blood-thinning medication. Use of ginseng and other supplements or medications should be discussed with a physician. Individuals who smoke are encouraged to quit as smoking significantly increases risk for blood clots.

Therapy

Special support hose called compression stockings can be used to help improve blood circulation. Blood-thinning medication may be prescribed for individuals with a history of a blood clot.

Prognosis

The location of the blood clot and how much the clot has obstructed blood flow determines the prognosis. The death rate for arterial embolism is 25-30%.

Approximately 25% of arterial embolism cases require amputation .

Prevention

Regular exercise enhances blood circulation and helps to prevent blood clots. Performing frequent leg exercises when immobile for extended periods of time, such as long distance travel, can maintain adequate blood flow. Not crossing the legs and not wearing tight-fitting clothes below the waist are also beneficial. Individuals should take measures to prevent the development of coronary artery disease, which increases the risk of blood clot formation. These measures include losing weight if overweight, decreasing stress , maintaining physical fitness, and not smoking.

QUESTIONS TO ASK YOUR DOCTOR

• What steps can I take to reduce my risk of serious complications from a blood clot?
• Am I at increased risk for a heart attack, stroke, or pulmonary (lung) embolism?
• What lifestyle changes can I make to decrease my risk of a blood clot?
• Will I always be at risk for development of a blood clot?
• Will I need to take medication to reduce my risk of developing a blood clot?

Caregiver concerns

Knowing the warning signs and symptoms of a blood clot may enable rapid diagnosis and treatment and thus avoid serious complications. It is important to know the side effects of anticoagulant and antiplatelet medications. Unusual bruising , bleeding that does not stop, headache, dizziness, trouble breathing, chest pain, nosebleed, bleeding gums, red or dark urine, or red or black color in the stool should be reported to a physician immediately.

Anticoagulant medication therapy requires regular blood testing. Activities that can result in serious injury should be avoided if anticoagulation or anti-platelet medication is being used. Vitamin K is involved in the blood clotting process so intake of Vitamin K foods in the diet should be closely monitored. Some over-the-counter (OTC) and prescription medications interfere with certain anticoagulant medicines; a physician should be consulted before starting any medication. An identification card listing the medication being taken should be carried by patients on either of these two types of medication.

Resources

OTHER

“Are You at Risk for Blood Clots?” DNADirect. December 6, 2007 [cited April 5, 2008]. http://www.dnadirect.com/patients/tests/blood_clotting/more_about/GH_Thr_Risk.jsp.

“Blood Clot Prevention: Battling a Dangerous Condition.” LifeExtension January 19, 2006 [cited April 5, 2008]. http://www.lef.org/protocols/heart_circulatory/blood_clot_01.htm

Matsui, William. “Blood Clots.” MedlinePlus. November 2, 2006 [cited April 5, 2008]. http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm.

June G. Borazjani RN, MSN, CPHQ

Blood Clotting

Blood clotting (coagulation) is the process by which blood vessels repair ruptures after injury. Injury repair actually begins even before clotting does, through vascular spasm, or muscular contraction of the vessel walls, which reduces blood loss. Clotting itself is a complex cascade of reactions involving platelets, enzymes , and structural proteins .

Platelets are not whole cells, but rather small packets of membrane-bounded cytoplasm . There are approximately one million platelets in a drop of blood. Damage to the lining of a blood vessel (the endothelial lining) exposes materials that cause platelets to stick to the endothelial cells; additional platelets then stick to these. These aggregating platelets release factors that promote accumulation of fibrin, a circulating protein. A blood clot is a meshwork of platelets and blood cells woven together by fibrin.

Accumulation of fibrin must be tightly regulated, of course, to prevent clot formation where there is no wound. Thrombosis is an abnormal localized activation of the clotting system. Disseminated intravascular coagulation is a pathological condition in which the clotting system is activated throughout the circulatory system in response to bacterial toxins, trauma, or other stimuli. A clot may break off, forming an embolus, which can lodge in a small blood vessel, cutting off circulation. If this occurs in the heart, it may cause ischemia (lack of blood flow) or myocardial infarction (heart attack). In the lungs, it causes pulmonary embolism, with loss of capacity for oxygen exchange. In the brain, it can cause stroke.

Because of this need for tight regulation, and the need for rapid response, the clotting mechanism involves a multistep cascade of enzymes, most of whose jobs are to activate the next enzyme in the cascade. In this way, the effect of the initial stimulus (the damaged blood vessel) can be quickly magnified, as a single enzyme at the first stage activates many copies of another enzyme at the next stage, each of which activates many more at the next, and so on. At the same time, the many levels of interaction provide many points of control over the process. This coagulation cascade begins from thirty seconds to several minutes after the injury.

Coagulation can begin with either of two pathways, called the extrinsic and intrinsic pathway, both of which feed into a common pathway that completes the process. The extrinsic pathway begins with a substance called tissue factor (tissue thromboplastin) released by damaged blood vessels and surrounding tissues. In the presence of other plasma proteins (clotting factors) and calcium ions , this leads to the activation of a protein called factor X. The intrinsic pathway begins with a substance called factor XII, released by blood platelets. Through a series of additional clotting factors, and again in the presence of calcium ions, this pathway also leads to the activation of factor X. One of the necessary factors of the intrinsic pathway is called factor VIII. A mutation in the gene for this factor is the most common cause of hemophilia.

The common pathway begins with the activation of factor X. In the presence of calcium ions and other clotting factors, factor X activates an enzyme called prothrombin activator. This enzyme them converts the plasma protein prothrombin into thrombin. Thrombin is an enzyme that, in turn, converts fibrinogen to fibrin. Here the cascade ends, because fibrin is not an enzyme, but a fibrous protein. It forms strands that stick to the platelets and endothelial cells at the wound, forming a meshwork that, in turn, traps other cells.

Once the clot forms, contraction of the platelets pulls the edges of the wound closer together, and fresh endothelial cells then grow across it, repairing the damaged blood vessel. Over time, fibrin is degraded by plasmin. This enzyme is formed from circulating plasminogen by tissue plasminogen activator (t-PA). Synthetic t-PA is used to dissolve blood clots in stroke, myocardial infarction, pulmonary embolism, and other conditions.

see also Blood; Blood Vessels; Control Mechanisms

Richard Robinson

Bibliography

Guyton, Arthur C., and John E. Hall. Textbook of Medical Physiology, 10th ed. Philadelphia, PA: W. B. Saunders, Co., 2000.

Stiene-Martin, E. Anne, Cheryl A. Lotspeich-Steininger, and John A. Koepke. Clinical Hematology: Principles, Procedures, Correlations, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 1998.

blood clotting Blood which is withdrawn or spilt from the body will separate within minutes into dark red clot and straw-coloured serum. It is normally prevented from clotting (or ‘coagulating’) in the circulation, but there are substances always present in the blood which will cause clotting when there is a need to plug a damaged vessel. Clotting at a site of injury involves enzymes, several specific proteins made in the liver, calcium ions, and platelets — all present in the blood — together with substances released from damaged tissue. Their interaction produces fibrin, the stringy framework of a clot. Clots may form inside intact blood vessels where there is an abnormality of the lining, or where blood is unduly static. A clot is also known as a thrombus, and the condition of abnormal clot formation, thrombosis. A tendency to thrombosis can be counteracted by substances which interfere at some stage of the process: e.g. heparin or warfarin, and aspirin is used as a long-term preventative measure. The downside of such anticoagulant treatments is a tendency to bleed more easily.

Stuart Judge