Related Terms

• ADAMTS13 enzymes, antiphospholipid syndrome, aspirin, aspirin-induced bleeding, bleeding disorders, blood, blood cells, blood clotting factors, blood pooling, blood vessels, coagulate, coagulation, clotting, clotting disorders, deep vein thrombosis, DIC, disseminated intravascular coagulation, drug-induced immune thrombocytopenia, drug-induced non-immune thrombocytopenia, factor X, factor Xa, hemophilia, hemolytic uremic syndrome, hemorrhage, hemorrhagic disease of the newborn, hemostasis, heparin, homocysteine, HUS, hyperhomocysteinemia, hypoprothrombinemia, idiopathic thrombocytopenic purpura, immune thrombocytopenia, platelet aggregation, platelet inhibition, platelets, pulmonary embolism, red blood cells, thrombocytopenia, thrombin, thrombosis, thrombus, vitamin K deficiency, VKDB, von Willebrand factor, von Willebrand's disease, warfarin.

Background

• Coagulation disorders occur when the blood does not form clots properly. Blood clots are clumps of different types of blood cells and clotting factors that stop bleeding after an injury. Patients with coagulation disorders may develop too many blood clots that eventually block blood vessels, while others may not clot enough and have excessive bleeding in the body. Both of these conditions range from mild to severe and life threatening.

• The process of blood clotting is called coagulation or hemostasis. There are three major phases of coagulation: narrowing of blood vessels, activation of platelets, and activation of blood clotting factors.

• Phase 1: When a blood vessel (vein or artery) becomes injured, it narrows to slow blood flow so that clotting can begin. At the same time, the blood that has leaked outside of the injured blood vessel presses against the vessel to help prevent further blood loss.

• Phase 2: Blood cells called platelets are activated to move towards the site of injury. The platelets produce a substance called von Willebrand factor, which has a major role in blood coagulation and helps platelets stick to the blood vessel's walls.

• Phase 3: Once platelets reach the site of injury, a series of reactions by enzymes called "coagulation factors" lead to the activation of a protein called thrombin. This protein converts a blood clotting factor, called fibrinogen, into long strands that form a net around the platelets and blood cells. This net helps trap more platelets to form a blood clot.

• The blood clot, also called a thrombus, is a temporary plug to control bleeding. Once the platelets are clumped together, they change in shape from round to spiny. Sometimes blood clots are visible, and they appear as bruises on the skin.

• Once the blood vessel is healed, other blood factors are released to destroy the clot. The clot is then dissolved into the blood.

• Abnormalities in the clotting process can lead to coagulation disorders, such as thrombocytopenia or hemophilia. These disorders may be long-term inherited conditions or temporary conditions that are triggered by surgery, severe injuries, or other medical conditions (e.g. arterial fibrillation or heart attack).

• When there is too much clotting, small blood vessels can become clogged. When a patient's vein is blocked with a clot, the condition is called venous thrombosis. As a result of excessive clotting, blood flow is limited or completely blocked through the blood vessel. Depending on where the blockage occurs, the condition can be potentially fatal. For instance, if arteries in the heart are blocked, it may lead to a heart attack.

• In some cases, a blood clot may form and travel through the blood vessels. Eventually, this free-floating clot may become too large to pass through a vein or artery, and the clot may become lodged in the vessel.

• When blood does not clot effectively, as occurs with certain conditions, such as hemophilia or von Willebrand disease, even a minor injury to a blood vessel may lead to serious blood loss.

• Most coagulation disorders affect multiple veins and arteries. The veins in the legs are the most commonly affected blood vessels. Blood clots in the veins of the legs are a potentially life-threatening condition called deep vein thrombosis (DVT). DVT is considered a dangerous condition because small pieces of the blood clot can break off and travel to the heart, lungs, or brain. If a clot blocks an artery in the lungs, it is called a pulmonary embolism. If a blood vessel to the brain becomes blocked, it is called a stroke.

Causes

• General: Coagulations disorders may be long-term inherited conditions, or they may be temporary conditions caused by surgery, severe injury, medications, or infections. Other factors, including age, weight, lifestyle, and coexisting medical conditions, may contribute to the development of coagulation disorders.

• Thrombocytopenia: Thrombocytopenia is the most common cause of coagulation disorders. It is characterized by a lack of circulating platelets in the blood. Healthy individuals have anywhere from 150,000 to 450,000 platelets per microliter of circulating blood in the body. Thrombocytopenia occurs when the platelet count falls below 20,000 platelets per microliter of blood. The risk of bleeding increases as the number of platelets decreases. Mild thrombocytopenia often has no long-lasting effects. When there are less than 10,000 platelets per microliter of circulating blood, the condition is considered severe and internal bleeding (hemorrhage) may occur, especially in the brain or digestive tract.

• Disseminated intravascular coagulation (DIC) is a type of thrombocytopenia that occurs when the blood coagulates through the entire body, which causes a depletion of platelets. This disorder has variable effects. It can result in either clotting symptoms or, more often, bleeding. Bleeding can be severe. DIC may be stimulated by many factors, including bacterial or fungal infections in the blood, severe tissue injury (such as burns or head trauma), cancer, surgery, reactions to blood transfusions, or childbirth complications (such as retained placenta after delivery). Individuals suffering from this condition have an increased risk of bleeding. This disorder is most common among critically ill patients.

• Idiopathic thrombocytopenic purpura, also called immune thrombocytopenia, occurs when the immune system destroys platelets for an unknown reason. The body's immune system, which normally fights against disease and infection, attacks the platelets because they are mistaken for harmful invaders, such as bacteria. When the immune system mistakenly attacks body cells, the condition is called an autoimmune disease.

• Thrombotic thrombocytopenic purpura (TTP) is a rare disorder that is characterized by low levels of platelets, low levels of red blood cells, as well as abnormalities in the kidneys and nervous system. This blood disorder causes blood clots to form in blood vessels throughout the body. Most cases of TTP are the result of a deficiency of the ADAMTS13 enzymes, which are involved in clotting. Not having enough of this enzyme causes platelets to clump together. In TTP patients, clots form throughout the body as platelets bind together abnormally and stick to blood vessel walls. As the platelets clump together, there are fewer platelets available in the bloodstream. This can lead to purpura, which occurs when bleeding under the skin causes purple-colored spots to appear on the skin. It may also cause red blood cells to break apart and be destroyed prematurely. The condition is considered a medical emergency because, if left untreated, it can lead to hemolysis and organ damage.

• Drug-induced immune thrombocytopenia occurs when certain medications lead to the formation of antibodies that attack platelets. These antibodies bind to platelets and trigger other immune cells to destroy them. Some medications may cause the immune system to mistake the platelets for an invading substance and the antibodies set out to destroy the cells. As a result of this autoimmune response, platelets are removed rapidly from the blood circulation. Quinidine and quinine are the most common cause of the condition. However, both heparin and heroin have recently been indicated in an increasing number of reports.

• Drug-induced non-immune thrombocytopenia occurs when a medication reduces the number of healthy platelets in the blood. This is not an immune-mediated reaction. Instead, the drugs either directly destroy the platelets or damage the bone marrow where platelets are produced. Medications, such as heparin, aspirin, quinidine, quinine, sulfa-containing antibiotics, some diabetes medications (e.g. diazoxide), gold salts, and rifampin, may destroy platelets.

• Hemolytic uremic syndrome is a rare type of thrombocytopenia that causes a drastic decline in platelets, as well as the destruction of red blood cells and kidney damage. This condition has been caused by bacterial infections with Escherichia coli (E. coli). E.coli infections may develop after eating raw or undercooked meat, especially beef.

• Hemophilia: Hemophilia, or hemophilia A (Factor VIII deficiency), is an inherited coagulation disorder that causes excessive bleeding. This disorder is inherited as an X-linked recessive trait. Males are affected almost exclusively because they have one X and one Y chromosome, while females have two X chromosomes. If a male inherits one mutated X chromosome, he will have the disease. Females,onthe other hand,need to inherit two X chromosomes in order to develop the condition. Although females who have only one mutated X chromosome do not have the disorder, they can pass the chromosome onto their children.

• Hemophilia B, also called Factor IX deficiency or Christmas disease, is less common than hemophilia A. Patients with this disorder are born with low levels of a clotting factor called Factor IX. Without this factor, the blood is unable to clot properly.

• Hemorrhagic disease of the newborn (vitamin K deficiency bleeding/VKDB): Hemorrhagic disease of the newborn is a bleeding disorder that occurs during an infant's first few days of life. This happens when a baby is born with low levels of vitamin K, which is an important element in the clotting cascade. Patients with this disorder experience increased bleeding until they have adequate levels of vitamin K in the blood. In order to prevent this condition, newborns are given an injection of vitamin K shortly after birth.

• Von Willebrand's disease: Von Willebrand's disease is an inherited disorder that causes prolonged bleeding time. Patients are born with low or non-existent levels of a clotting factor called von Willebrand factor. In healthy patients, the platelets produce this clotting factor, which helps them stick to the blood vessel walls. Patients with this disease suffer from impaired platelet function.

• Hypoprothrombinemia: Hypoprothrombinemia occurs when a patient is born with low or non-existent levels of a clotting factor called prothrombin. As a result, the patient experiences an increased risk of bleeding.

• Hyperhomocysteinemia: Hyperhomocysteinemia occurs when a patient has high levels of an amino acid called homocysteine in the blood. As a result, the blood in the veins and arteries is more likely to clot.

• Hyperhomocysteinemia may be inherited or it may be caused by low levels of vitamin B6, vitamin B2, or folic acid. Less common causes of hyperhomocysteinemia include chronic kidney failure and the use of certain medications, including an anti-cancer drug called methotrexate, some anti-seizure drugs (e.g. phenytoin or carbamazepine), some cholesterol-lowering drugs (e.g. fibric acid derivatives or niacin), and the antibiotic isoniazid.

• Antiphospholipid syndrome: Antiphospholipid syndrome is a rare inherited disorder in which the body produces antibodies to proteins in the blood. Antiphospholipid syndrome may cause clots to form in the large veins of the legs and sometimes the arms. This potentially life-threatening condition is called deep vein thrombosis (DVT).

• Obesity: Patients who are obese have an increased risk of developing blood clots because the extra body weight puts pressure on the veins, which slows the flow of blood. Also, physical activity in obese patients is limited. This may cause blood pooling, which leads to clot formations, especially in the legs.

• Co-existing medical conditions: Certain medical conditions, including atherosclerosis (hardening of the arteries), arterial fibrillation, heart attack (myocardial infarction or MI), polyarteritis nodosa, which causes the blood vessels to swell, and giant cell arteritis, which causes the medium and large blood vessels in the head to swell, may make blood more likely to clot in the arteries. These disorders damage the arteries, which stimulate blood clot formation.

• Immobility: Individuals who have sedentary lifestyles have an increased risk of developing blood clots. This is because sitting still for extended periods of time may slow blood flow, causing blood to accumulate in the veins, especially in patients who are at risk of developing blood clots. For instance, patients who are paralyzed or who are on bed rest for a long time have an increased risk of developing blood clots, especially in the deep veins in their legs. This condition is called deep vein thrombosis (DVT).

• Even sitting still for several hours on an airplane or in a car may increase the risk of blood clots, especially DVT.

• Age: The risk for blood clots increases with age. Men who are older than 55 years and women who are older than 60 years have the greatest risk of developing blood clots. The reason for this remains unknown. Some researchers suggest that the increased risk of blood clots in the arteries may be associated with an increased risk of atherosclerosis (hardened arteries).

Signs and Symptoms

• General: In general, patients with anticoagulation disorders suffer from either increased bleeding or clotting. However, patients with disseminated intravascular coagulation may have symptoms of both bleeding and clotting.

• Increased clotting: Symptoms depend on which blood vessels are blocked with clots.

• If a blood vessel in an arm or leg is blocked, it may cause swelling and pain. The area may also become itchy and reddish brown in color. When this happens, the skin may be easily injured, often resulting in an ulcer.

• Pieces of blood clots from the veins in the legs, abdomen, or pelvis can travel through the bloodstream to the lungs and block major arteries. If blood vessels in the lungs are blocked, the condition is called a pulmonary embolism. Symptoms may include shortness of breath, wheezing, chest pain, increased heartbeat, leg swelling, dizziness, or coughing up blood. Patients who develop any of these symptoms should seek immediate medical treatment because a pulmonary embolism may lead to death.

• If blood vessels in the liver are blocked, symptoms may include yellowing of the skin and eyes (jaundice) and abdominal tenderness. Patients who develop any of these symptoms should seek immediate medical treatment.

• If blood vessels in the brain become blocked, the patient may suffer from a stroke. Symptoms may include sudden onset of numbness or weakness, difficulty speaking, confusion, difficulty seeing with one or both eyes, headache, dizziness, and imbalance. Patients who develop any of these symptoms should seek immediate medical treatment.

• If arteries to the heart become clogged, the patient may have a heart attack. Symptoms may include chest pain or pressure, shortness of breath, nausea, weakness, as well as pain radiating to the arms, neck, or jaw, Patients who develop any of these symptoms should seek immediate medical treatment.

• Small areas on the fingers or toes may turn black in color if fibrin, a component of blood clots, accumulates in the blood vessels.

• Increased bleeding: Patients with bleeding disorders, such as hemophilia, bleed for prolonged periods of time after injury. It may take hours for a small cut or nosebleed (epistaxis) to stop without treatment.

• Tiny red dots, called petechiae, may occur if there is bleeding under the skin. This condition is called purpura. Patients may bruise easily. The gums may bleed, and blood may appear in the stool or urine. Internal bleeding may cause the joints to swell and become painful.

• Patients may develop internal bleeding that may lead to organ damage or even death. Internal bleeding may not cause any distinctive symptoms.

Diagnosis

• General: If a coagulation disorder is suspected, a healthcare provider will take a detailed medical history and perform a physical examination. It is important for patients to tell their healthcare providers if they are trying a new diet or taking any new drugs (prescription or over-the-counter), herbs, or supplements (e.g. aspiring, salicylate-containing agents, nonsteroidal anti-inflammatory drugs, or vitamin K) because they may be causing the disorder or worsening symptoms

• Blood tests: Coagulation disorders are diagnosed after blood tests are performed. A sample of the patient's blood is analyzed for the presence of clotting factors, including platelets, vitamin K, Factor VIII, Factor IX, von Willebrand factor, and other blood proteins. Patients with abnormal levels of these proteins are diagnosed with coagulation disorders.

• DNA analysis: A DNA analysis may be performed to determine whether or not the patient has inherited a disorder, such as hemophilia. During the procedure, a sample of blood is taken from the patient and sent to a laboratory for analysis. If a mutated gene associated with a specific disorder is present, a positive diagnosis is made.

• Antibody testing: If it is suspected that the condition may be autoimmune-related, such as idiopathic thrombocytopenia, a healthcare provider will take a sample of the patient's blood to determine whether or not autoantibodies are present. Autoantibodies bind to the patient's own cells, causing the immune system to attack the body. If autoantibodies are present, the patient has an autoimmune disorder.

Treatment

• General: Treatment varies depending on the specific type and severity of the coagulation disorder. Patients should tell their healthcare providers if they are taking any other drugs (prescription or over-the-counter), herbs, or supplements because they may interact with treatment.

• Anticoagulants: Anticoagulants, such as warfarin (Coumadin®), enoxaparin (Lovenox®), or heparin, are used to prevent blood clots from forming. These drugs are commonly called blood-thinners. Patients typically receive a combination of warfarin and heparin when they are first diagnosed with a blood clotting disorder. Then, depending on the specific condition, warfarin may need to be taken for the rest of the patient's life. Enoxaparin is commonly used to prevent deep vein thrombosis (DVT) in patients who are on bed rest.

• Anti-platelet drugs: Anti-platelet drugs, also called platelet aggregation inhibitors, have been used to prevent platelets from forming clots. Examples include aspirin, clopidogrel (Plavix®), and cilostazol (Pletal®).

• Clotting factors: Hemophiliacs may receive injections with clotting factors, either taken from donated human blood or produced in a laboratory using recombinant technology. This helps the body clot properly. Some patients may require repeated infusions if the internal bleeding is severe. Some healthcare providers may recommend preventative treatment with injections of clotting factors to help avoid future bleeding episodes.

• Blood transfusions: Patients who suffer from severe bleeding may receive blood transfusions with donated blood. This helps restore the lost blood.

• Patients with severe cases of thrombocytopenia may receive platelet concentrates.

• Plasmapheresis: Thrombotic thrombocytopenic purpura (TTP) requires emergency treatment with plasmapheresis. During plasmapheresis, plasma (which contains platelets) from a blood donor is transfused into the TTP patient's blood. Plasmapheresis is continued until the platelet count normalizes and there is minimal breakdown of red blood cells (hemolysis).

• Corticosteroids and/or immunosuppressants: Patients with mild idiopathic thrombocytopenic purpura usually do not require treatment. Patients who have moderate to severe cases typically receive medications that block the antibodies that attack platelets, such as corticosteroids (like prednisone), or medications that suppress the immune system to reduce antibody formation, such as cyclophosphamide (Cytoxan®) or azathioprine (Imuran®). Treatment is generally continued for the rest of the patient's life.

• Desmopressin: Patients who have coagulation disorders that cause increased bleeding may receive a slow injection of the hormone desmopressin (DDAVP). This hormone stimulates the body to release clotting factors to stop bleeding. Sometimes desmopressin is given as a nasal spray.

• Vitamin K: Low levels of vitamin K may lead to increased bleeding, especially in infants. That is why newborns typically receive injections of vitamin K shortly after birth. Vitamin K is found in green leafy vegetables, such as spinach, broccoli, asparagus, watercress, cabbage, cauliflower, green peas, beans, olives, canola, soybeans, meat, cereals, and dairy products. Patients should talk to their healthcare providers and/or pharmacists before taking vitamin K supplements.

• Patients who are already receiving coagulation therapy should not drastically change their eating habits unless they consult their healthcare providers first. Significant changes in vitamin K consumption may have an impact on the effectiveness of treatment.

Integrative Therapies

• Strong scientific evidence:

• Policosanol: Policosanol is a natural product made from the waxy coating of sugar cane that helps lower cholesterol. Various studies have found that policosanol causes inhibition of platelet aggregation.

• Avoid if allergic or hypersensitive to policosanol. Use cautiously with nitrates, aspirin, or drugs that lower cholesterol or blood pressure. Avoid if pregnant or breastfeeding.

• Vitamin K: Vitamin K is found in green leafy vegetables, such as spinach, broccoli, asparagus, watercress, cabbage, cauliflower, green peas, beans, olives, canola, soybeans, meat, cereals, and dairy products. Vitamin K deficiency in infants may lead to hemorrhagic disease of the newborn, also known as vitamin K deficiency bleeding (VKDB). Although almost half of newborns may have some degree of vitamin K deficiency, serious hemorrhagic disease is rare. Because vitamin K given by injection has been shown to prevent VKBD in newborns and young infants, the American Academy of Pediatrics recommends administering a single intramuscular injection of vitamin K1 to all newborns. Oral dosing is not considered adequate as prevention, particularly in breastfeeding infants. Initial concerns of cancer risk have not been proven and are generally not considered clinically relevant. In cases of true VKDB, bleeding may occur at injection sites, at the umbilicus, or in the gastrointestinal tract. Life-threatening bleeding into the head (intracranial) or in the area behind the lower abdomen (retroperitoneum) may also occur. Evaluation by a physician is imperative.

• Warfarin (Coumadin®) is a blood-thinning drug that inhibits vitamin K-dependent clotting factors. Warfarin is prescribed by doctors for people with various conditions, such as arterial fibrillation, artificial heart valves, history of serious blood clot, clotting disorders (hypercoagulability), or placement of indwelling catheters/ports. Usually, blood tests are done regularly to evaluate the extent of blood thinning, using a test for prothrombin time (PT) or International Normalized ratio (INR). The range for the PT/INR depends on the condition being treated. Elevated PT/INR may result from many causes and sometimes can be dangerously high and increase the risk of serious bleeding. Patients taking warfarin should be aware of these potential causes, which include many drugs that interact with warfarin, liver disorders, or accidental warfarin overdose. Because the effects of warfarin on anticoagulation are usually delayed several days, the PT/INR may not increase immediately at the time of overdose. If a person's blood becomes too "thin," treatment should be under strict medical supervision and may include oral or injected vitamin K to help reverse the effects of warfarin.

• Avoid if allergic or hypersensitive to vitamin K. Injection into the muscle or vein should only be done by a healthcare professional. Many serious side effects have occurred after injection. Menadiol, a type of vitamin K that is not available in the United States, should be avoided with glucose-6-phosphate dehydrogenase deficiency. Avoid if pregnant. Large amounts of vitamin K may cause serious side effects or death. Vitamin K is generally considered safe for breastfeeding mothers.

• Unclear or conflicting scientific evidence:

• Aortic acid: Aortic extract is usually made from the hearts of animals, usually sheep, cows, or pigs. There are many substances in this extract, including aortic acid, which is a broad term encompassing several constituents. Mesoglycan is the most studied of these constituents. Further research is needed to determine whether or not aortic acid may help treat patients with deep vein thrombosis (DVT).

• Allergic reactions have not been reported in the available literature. Due to the heparan sulfate content of mesoglycan, patients with an allergy to heparin or heparinoid derivatives should use caution. Use cautiously with coagulation (blood) disorders or in patients taking anticoagulation therapy. Use cautiously with hypertension (high blood pressure) or in patients taking antihypertensive drugs. Avoid if pregnant or breastfeeding.

• Garlic: The garlic bulb is made of many cloves that are wrapped in a paper-thin, white skin. Garlic, which is often used as a spice in food, has also been used to treat many medical conditions. In humans, garlic has been studied for its anti-platelet effects and potential use as an anticoagulant therapy. Because garlic has been associated with several cases of bleeding, therapy should be used cautiously, especially in patients who are taking other medications, herbs, or supplements that may increase the risk of bleeding.

• Avoid if allergic or hypersensitive to garlic or other members of the Lilaceae(lily) family (e.g. hyacinth, tulip, onion, leek, or chive). Avoid with a history of bleeding problems, asthma, diabetes, low blood pressure, or thyroid disorders. Stop using supplemental garlic two weeks before and immediately after dental/surgical/diagnostic procedures to avoid bleeding problems. Avoid supplemental doses if pregnant or breastfeeding.

• Ginger: The underground stems (rhizomes) and above ground stems of ginger have been used in Chinese, Japanese, and Indian medicine for hundreds of years. One study suggests that ginger may increase the anti-platelet effects of the medication nifedipine in patients who have high blood pressure. Further research is necessary to determine if ginger might be used as an anticoagulant therapy.

• Avoid if allergic to ginger or other members of the Zingiberaceaefamily, including red ginger, Alpinia purpurata, shell ginger, Alpinia zeru, green cardamom, or Balsam of Peru. Use cautiously if driving or operating machinery because ginger may cause drowsiness. Stop two weeks before and immediately after surgery/dental/diagnostic procedures due to risk of bleeding. Avoid with a history of irregular heartbeat (arrhythmia). Use cautiously with a history of ulcers, acid reflux, heart conditions, inflammatory bowel disease, blocked intestines, or bleeding disorders. Use cautiously if pregnant or breastfeeding.

• Grape seed: Early human and animal studies show that extracts of grape seed may block the ability of platelets to form a clot (resulting in "thinner" blood). In clinical study, grape seed constituents have resulted in inhibition of platelet aggregation, however additional research is needed to better determine these effects and applicable patient populations.

• Avoid if allergic or hypersensitive to grapes or other grape compounds. Use cautiously if taking blood thinners such as warfarin, aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), or anti-platelet agents. Use cautiously with bleeding disorders or if taking drugs that may increase the risk of bleeding. Use cautiously with drugs processed using the liver's "cytochrome P450" enzyme system. Use cautiously with blood pressure disorders or if taking ACE inhibitors. Avoid with disorders that increase the risk of bleeding or with active bleeding disorders (stomach ulcers, bleeding into the brain, etc.). Avoid if pregnant or breastfeeding.

• Pycnogenol: Pycnogenol® is the patented trade name for a water extract of the bark of the French maritime pine (Pinus pinaster ssp. atlantica), which is grown in coastal southwestern France. Pycnogenol® contains oligomeric proanthocyanidins (OPCs), as well as several other bioflavonoids: catechin, epicatechin, phenolic fruit acids (such as ferulic acid and caffeic acid), and taxifolin. According to the results of limited available human study, Pycnogenol® may cause inhibition of platelet aggregation in smokers. However, further research is needed before a firm conclusion can be made.

• Pycnogenol® treatment may effectively decrease the number of thrombotic events (deep vein thrombosis and superficial vein thrombosis) in moderate- to high-risk subjects, during long-haul flights. Edema (swelling) may also be reduced. Further research is needed to confirm these results.

• Avoid if allergic or hypersensitive to Pycnogenol®, its components, or members of the Pinaceae family. Use cautiously with diabetes, hypoglycemia, bleeding disorders. Use cautiously if taking hypolipidemic agents (drugs that lower cholesterol), medications that may increase the risk of bleeding, hypertensive medications, or immune stimulating or inhibiting drugs. Avoid if pregnant or breastfeeding.

• Rutin: Rutin is a yellow crystalline flavonol glycoside that occurs in various plants, especially the buckwheat plant, black tea, apple peels, onions, and citrus. Limited available clinical study suggests that a rutin-containing drug called Venoruton®, in combination with elastic compression or thrombectomy, may offers benefit as compared to these treatments alone for patients with superficial vein thrombosis (SVT). Additional study is needed in this area.

• Avoid if allergic or hypersensitive to O-(beta-hydroxyethyl)-rutosides or plants that rutin is commonly found in, such as rue, tobacco, or buckwheat. Use cautiously in elderly patients. Use cautiously with skin conditions. Use cautiously if taking medications for edema, diuretics, or anticoagulation medications (e.g. heparin or warfarin). Use cautiously if pregnant or breastfeeding.

• Seaweed, kelp, bladderwrack: Bladderwrack (Fucus vesiculosus) is a brown seaweed found along the northern coasts of the Atlantic and Pacific oceans and North and Baltic seas. Another seaweed that grows alongside bladderwrack is Ascophyllum nodosum, andit is often combined with bladderwrack in kelp preparations. Laboratory study has found anticoagulant properties in fucans or fucoidans, which are components of brown algae such as bladderwrack. However, there are no high quality human studies available to support this use.

• Avoid if allergic or hypersensitive to Fucus vesiculosus or iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.

• Shea butter: In clinical trials, shea butter/oil was shown to lower increases in postprandial factor VII coagulant concentrations. Additional trials with larger sample sizes are needed to confirm the anticoagulant effects of shea butter.

• Use cautiously in patients taking anticoagulants. Use cautiously in patients with a latex allergy as anecdotal information suggests that some formulations of shea butter may contain latex.

• TENS (transcutaneous electrical nerve stimulation): TENS (transcutaneous electrical nerve stimulation) is a non-invasive technique in which a low-voltage electrical current is delivered through wires from a small power unit to electrodes located on the skin. Electrodes are temporarily attached with paste in various patterns, depending on the specific condition and treatment goals. TENS has been suggested as a possible treatment for skin flap ischemia. TENS has been tested for its effects on blood flow to skin flaps used in plastic surgery procedures, such as breast reconstruction. Currently, there is not enough reliable evidence to draw a firm conclusion in this area.

• Avoid with implantable devices, such as defibrillators, pacemakers, intravenous infusion pumps, or hepatic artery infusion pumps. Use cautiously with decreased sensation (such as a nerve disorder called neuropathy) or with seizure disorders. Avoid if pregnant or breastfeeding.

• Turmeric: Early research suggests that turmeric may prevent the formation of blood clots. More research is needed before turmeric can be recommended for blood clot prevention.

• Avoid if allergic or hypersensitive to turmeric, curcumin, yellow food colorings, or plants belonging to the Zingiberaceae (ginger) family. Use cautiously with a history of bleeding disorders, immune system deficiencies, liver disease, diabetes, hypoglycemia, or gallstones. Use cautiously with blood-thinners, such as warfarin (like Coumadin®), and blood sugar-altering medications. Avoid in medicinal amounts if pregnant or breastfeeding. Turmeric should be stopped prior to scheduled surgery.

• Vitamin E: Preliminary data suggests that supplementation with vitamin E may reduce the risk of venous thromboembolism (VTE) in women, and those with a prior history or genetic predisposition may particularly benefit. Additional research is needed to confirm these results.

• Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid above the recommended daily level in pregnant women and breastfeeding women.

• Yohimbe bark extract: The terms yohimbine, yohimbine hydrochloride, and yohimbe bark extract are all related. However, they all have slightly different meanings. Yohimbine is found in the bark of the Pausinystalia yohimbe tree. Yohimbine hydrochloride is a standardized form of yohimbine that is available as a prescription drug in the United States. Pre-clinical studies report that yohimbine alkaloids, constituents of yohimbe bark, may cause inhibition of platelet aggregation. Research in humans is limited, and more research is necessary in this area.

• Yohimbine is generally well tolerated in recommended doses. However, many side effects have been reported with yohimbine hydrochloride and may apply to yohimbe bark. Avoid if allergic to yohimbe, any of its components, or any ingredients in yohimbine-containing products. Use cautiously with peptic ulcer disease, kidney disease, high blood pressure, heart disease, or if taking drugs that affect blood sugar levels. Avoid with benign prostate hypertrophy (enlarged prostate), anxiety, mania, depression, stress disorders, post-traumatic stress disorders, bipolar disorders, or schizophrenia. Avoid use in children or in pregnant or breastfeeding women.

• Fair negative scientific evidence:

• Boron: Boron is an element that is found around the world. Boron can enter the body through the skin, lungs, or mouth. It has been proposed that boron may affect the activity of certain blood clotting factors. Study results are conflicting and there is therefore currently not enough evidence to form a clear conclusion of boron's potential to cause prevention of blood clotting.

• Avoid if allergic or sensitive to boron, boric acid, borax, citrate, aspartate, or glycinate. Avoid with a history of diabetes, seizure disorder, kidney disease, liver disease, depression, anxiety, high blood pressure, skin rash, anemia, asthma, or chronic obstructive pulmonary disease (COPD). Avoid with hormone-sensitive conditions, such as breast cancer or prostate cancer. Avoid if pregnant or breastfeeding.

Prevention

• General: Some types of coagulation disorders, such as those that are inherited, cannot be prevented. However, individuals can take steps to reduce their risks of developing blood clots or excessive bleeding that can be caused or made worse by certain lifestyle or nutritional habits.

• Exercise: Regular exercise may help reduce the risk of blood clots. This is because sitting still for extended periods of time may slow blood flow, causing blood to accumulate in the veins, especially in patients who are at risk of developing blood clots.

• Patients who are paralyzed or on bed rest after surgery should talk to their healthcare providers about recommended exercises. A physical therapist may be recommended to improve mobility in patients who are injured or suffer from disabilities.

• Patients who are sitting on airplanes for several hours should stand up and stretch every hour. If possible, walk up and down the aisle a few times during a flight to increase blood flow. Patients on long car, bus, or train trips are likewise advised to get up every couple of hours and stretch their legs. Avoid crossing the legs because that may increase the pressure on the blood vessels.

• Weight control: Weight control may help prevent blood clots from forming. Obese patients are more likely to develop blood clots because the extra weight puts pressure on the veins and reduces blood flow.

• Vitamin K: Low levels of vitamin K in the blood may lead to an increased risk of bleeding. Therefore, patients should consume a healthy and balanced diet that is rich in vitamin K. Vitamin K is found in green leafy vegetables like spinach, broccoli, asparagus, watercress, cabbage, cauliflower, green peas, beans, olives, canola, soybeans, meat, cereals, and dairy products. Newborns should receive an injection of vitamin K shortly after birth to avoid bleeding problems. Patients should consult their healthcare providers before taking vitamin K supplements.

• Patients who are already receiving coagulation therapy should not drastically change their eating habits unless they consult their healthcare providers first. Significant changes in vitamin K consumption may have an impact on the effectiveness of treatment.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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6. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

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8. Teitel J, Berntorp E, Collins P, et al. A systematic approach to controlling problem bleeds in patients with severe congenital haemophilia A and high-titre inhibitors. Haemophilia. 2007 May;13(3):256-63. View Abstract.