Gregory YH Lip, MD, FRCPE, FESC, FACC
Graham F Pineo, MD
Kenneth A Bauer, MD
Lawrence LK Leung, MD
Stephen A Landaw, MD, PhD
DEEP VEIN THROMBOSIS OVERVIEW — Venous thrombosis is a condition in which a blood clot (thrombus) forms in a vein. This clot can limit blood flow through the vein, causing swelling and pain. Most commonly, venous thrombosis occurs in the “deep veins” in the legs, thighs, or pelvis (figure 1); this is called a deep vein thrombosis, or DVT.
Venous thrombosis can form anywhere in the venous system. However, DVT is the most common type of venous thrombosis. If a part or all of the blood clot in the vein breaks off from the site where it was created, it can travel through the venous system; this is called an embolus. If the embolus lodges in the lung, it is called pulmonary embolism (PE), a serious condition that leads to over 50,000 deaths a year in the United States. In most cases, PE is caused by a DVT when part of a blood clot breaks off and lodges in the lung. The term “venous thromboembolism” is sometimes used when discussing both DVT and PE.
This topic review discusses the risk factors, signs and symptoms, diagnostic process, and treatment of a deep vein thrombosis. The diagnosis and treatment of pulmonary embolisms are discussed separately. (See “Patient information: Pulmonary embolism”.)
DEEP VEIN THROMBOSIS RISK FACTORS — There are a number of factors that increase a person’s risk of developing a deep vein thrombosis.
Inherited thrombophilia — Inherited thrombophilia refers to a genetic problem that causes the blood to clot more easily than normal. Various factors in the blood clotting process may be involved, depending on the type of genetic problem present.
An inherited thrombophilia is frequently present in people with a venous blood clot (ie, thrombus). Deficiencies of antithrombin, protein C, or protein S can be found in up to 15 percent of patients who have had a venous blood clot and are less than 50 years of age. Other factors, such as factor V Leiden or the prothrombin gene mutation, are more common in Caucasian populations and can be found in all age groups. Venous thrombosis is infrequent before adolescence in people with inherited thrombophilia.
If a person is found to have a DVT and there is no known medical condition or recent surgery that could have caused the DVT, it is possible that an inherited condition is the cause. This is especially true in people with a family member who has also experienced a DVT or pulmonary embolism. In these cases, testing for an inherited thrombophilia is often recommended (see ‘Finding the cause of venous thrombosis’ below).
Elevated clotting factors — Having an increased level of one or more factors involved in blood clotting, such as factor VIII, increases the risk of a blood clot.
Medical conditions or medications — Some medical conditions and medications increase a person’s risk of developing a blood clot
- Heart failure
- Previous DVT or PE
- Increased age
- Cancer — Some cancers increase substances in the blood that cause blood to clot.
- Kidney problems, such as nephrotic syndrome (see “Patient information: The nephrotic syndrome”)
- Certain medications (eg, birth control pills, hormone replacement therapy, erythropoietin, tamoxifen, thalidomide). The risk of a blood clot is further increased in people who use one of these medications and smokes or is overweight.
Surgery and related conditions — Surgical procedures, especially those involving the hip, pelvis, or knee, increase a person’s risk of developing a blood clot. During the recovery period, this risk often continues because the person is less active. Inactivity during long trips can also increase a person’s risk of developing a blood clot. Precautions to reduce the risk of blood clots are discussed below (see ‘Deep vein thrombosis prevention’ below).
- Major surgery (especially orthopedic surgery and neurosurgery)
- Trauma, especially if blood vessels are injured
- Prolonged sitting, especially sitting for six or more hours on a plane, or bed rest
Acquired thrombophilia — Some types of thrombophilia are not inherited, but can increase a person’s risk of developing a blood clot.
- Certain disorders of the blood, such as polycythemia vera or essential thrombocythemia
- Antiphospholipid antibodies (antibodies in the blood that can affect the clotting process) (see “Patient information: The antiphospholipid syndrome”)
DEEP VEIN THROMBOSIS SYMPTOMS — The signs and symptoms of DVT may be caused by the clot, or may be related to another condition. Imaging studies are needed to determine if a clot is present.
Deep vein thrombosis — Classic symptoms of DVT include swelling, pain, warmth, and redness in the involved leg.
Superficial phlebitis — Superficial phlebitis (SP) causes pain, tenderness, firmness, and/or redness in a vein due to inflammation, infection, and/or a blood clot (thrombus). It is most commonly seen in the lower legs.
Superficial phlebitis differs from a deep vein thrombosis because the veins that are affected are near the surface of the skin. Symptoms of SP typically develop over hours to days and resolve in days to weeks. The area may continue to be firm for several weeks to months. Treatment usually includes heat, elevation of the leg, and an NSAID medication, such as ibuprofen (Advil, Motrin). In most people with SP, there is a low risk of developing a pulmonary embolism. Therefore, anticoagulation is not usually needed for patients with SP.
DEEP VEIN THROMBOSIS DIAGNOSIS — If the patient’s history, symptoms, and physical exam suggest a DVT, tests are needed to confirm this. Tests to diagnose DVT may include compression ultrasonography, contrast venography, magnetic resonance imaging (MRI), computed tomography (CT scan), and/or a blood test called D-dimer.
If a person with a DVT also has signs or symptoms of a pulmonary embolus, additional testing will be needed. (See “Patient information: Pulmonary embolism”.)
D-dimer — D-dimer is a substance in the blood that is often increased in people with venous thromboembolism or PE. The test can be used to eliminate the possibility of deep venous thrombosis. If the D-dimer test is negative and the patient has a low risk of DVT or PE based upon their history and physical examination, DVT or PE are unlikely and further testing may not be needed.
Compression ultrasonography — Compression ultrasonography uses sound waves to generate pictures of the structures inside the leg. For this type of exam, a person lies on their back and then their stomach as an ultrasound wand is applied to the leg. In most circumstances, compression ultrasonography is the test of choice for patients with suspected DVT.
Contrast venography — During contrast venography, a catheter is threaded into a vein and a dye is injected. This allows the clinician to see the vein with x-ray. Venography is generally reserved for situations in which ultrasound is not feasible, when other tests have not been helpful, or when other tests are negative but the clinician feels strongly that a venous thrombosis is present.
Magnetic resonance imaging (MRI) — MRI uses a strong magnet to produce detailed pictures of the inside of the body. Magnetic resonance venography is as accurate as contrast venography. MRI is expensive, and its use may be limited to situations in which contrast venography cannot be performed, such as in patients with poor kidney function, during pregnancy, or because of allergy to the dye required in contrast venography.
Finding the cause of venous thrombosis — After determining that a venous thrombosis is present, the clinician will want to know what caused it. In many cases, there are obvious risk factors such as recent surgery or immobility. (See ‘Acquired thrombophilia’ above.) In other cases, the clinician may test for the presence of an inherited form of thrombophilia or for another medical condition associated with an increased risk for venous thrombosis. (See ‘Inherited thrombophilia’ above.)
Persons with an acquired or inherited abnormality may require additional treatment or prevention measures to reduce the risk of another thrombosis. Some experts recommend that the family members of a person with an inherited thrombophilia be screened for the inherited condition if this information would impact their care, although this issue is controversial.
DEEP VEIN THROMBOSIS TREATMENT — The treatment of deep vein thrombosis and pulmonary embolism is similar. In DVT, the main goal of treatment is to prevent a PE. Other goals of treatment include preventing the clot from becoming larger, preventing new blood clots from forming, and preventing long-term complications of PE or DVT.
The primary treatment for venous thrombosis is anticoagulation. Other available treatments, which may be used in specific situations, include thrombolytic therapy or a filter in a major blood vessel (the inferior vena cava).
Anticoagulation — Anticoagulants are medications that are commonly called “blood thinners”. The medication does not actually thin the blood, but rather helps to prevent new blood clots from forming. Patients with venous thrombosis are usually treated first with an injectable anticoagulant. There are several such anticoagulants available, including:
- Unfractionated heparin, often given into a vein (intravenous)
- Low molecular weight heparin (enoxaparin/Lovenox®, dalteparin/Fragmin®, or tinzaparin/Innohep®)
- Fondaparinux (Arixtra®)
The choice of anticoagulant usually depends upon the healthcare provider’s preference, the patient’s medical condition, as well as cost issues.
These agents can all be injected under the skin (ie, subcutaneous injection) by the patient, a family member, or a home health nurse. This allows selected patients to be treated at home. Heparin, low molecular weight heparin, or fondaparinux are usually continued for at least five days, along with another medication called warfarin (Coumadin®). Warfarin is a pill that is taken by mouth. After approximately five days, the heparin, low molecular weight heparin or fondaparinux are discontinued while the warfarin is continued for at least three months.
Less commonly, the patient does not take warfarin but takes a daily injection of low molecular weight heparin or fondaparinux for the entire treatment period. Low molecular weight heparin and fondaparinux are more expensive than warfarin, but they do not need to be monitored with blood clotting tests.
For patients taking warfarin, the clotting factors in the blood need to be measured on a regular basis with a blood test called the International Normalized Ratio (INR). The target level INR for people on warfarin is usually between 2 and 3. (See “Patient information: Warfarin (Coumadin®)”.)
Duration of treatment — Warfarin (Coumadin®) is recommended for a MINIMUM of three months in a patient with DVT.
- In patients who had a reversible risk factor contributing to their DVT, such as trauma, surgery, cancer, or being confined to bed for a prolonged period, the person is often treated with anticoagulation for 3 months or until the risk factor is resolved.
- Expert groups recommend that people who develop a venous thrombosis and who do not have a known risk factor for thrombosis be treated with an anticoagulant for an indefinite period of time . However, this decision should be discussed with the person’s healthcare provider, beginning after three months of treatment and continuing on a regular basis thereafter. Some people prefer to continue the anticoagulant, which carries an increased risk of bleeding, while others prefer to stop the anticoagulant at some point, which may carry an increased risk for repeat thrombosis.
- People who have an underlying medical risk factor for thrombosis, such as the antiphospholipid syndrome, are advised to continue anticoagulation indefinitely after a first spontaneous DVT or PE.
- Most experts recommend continuing anticoagulation indefinitely for people with two or more episodes of venous thrombosis or if a permanent risk factor is present (eg, a mechanical heart valve).
Walking during DVT treatment — Once warfarin/heparin has been started and symptoms (eg, pain, swelling) are under control, the person is strongly encouraged to get up and walk around. Studies show that there is no increased risk of complications (eg, pulmonary embolus) in people who get up and walk, and walking may help the person to feel better faster.
Thrombolytic therapy — In some cases, a clinician will recommend an intravenous medicine to dissolve blood clots. This is called thrombolytic therapy. This therapy is more likely to be used in patients who have serious complications related to PE or DVT, or in patients with large blood clots in the leg who are at low risk of serious bleeding as a side effect of the therapy. The response to thrombolytic therapy is best when there is a short time between the diagnosis of DVT/PE and the start of thrombolytic therapy.
Inferior vena cava filter — An inferior vena cava (IVC) filter is a device that blocks the circulation of clots in the bloodstream. It is surgically placed in the inferior vena cava (the large vein leading from the lower body to the heart). An IVC filter is often recommended in patients with venous thromboembolism who cannot use anticoagulants because of recent surgery, a stroke caused by bleeding, bleeding in another area of the body.
It is also recommended in patients who develop recurrent thromboembolism despite anticoagulation, and in patients with pulmonary problems due to chronic recurrent embolism. It can also be used along with surgical procedures to remove blood clots.
DEEP VEIN THROMBOSIS PREVENTION
Surgical patients — Certain high-risk patients undergoing surgery (especially bone or joint surgery and cancer surgery) may be given anticoagulants to decrease the risk of blood clots. Anticoagulants may also be given to women at high risk for venous thrombosis during and after pregnancy.
In surgical patients with a moderate to low risk of blood clots, other preventive measures may be used. For example, some surgical patients are fitted with inflatable compression devices that are worn around the legs during and immediately after surgery and periodically fill with air. These devices apply gentle pressure to improve circulation and help prevent clots.
Graduated compression stockings may also be recommended; these stockings apply pressure to the lower legs, with the greatest pressure at the ankle. The pressure gradually decreases up to the knee. For all patients, walking as soon as possible after surgery can decrease the risk of a blood clot.
Extended travel — Prolonged travel appears to confer a two- to fourfold increase in risk of venous thromboembolism (VTE) . There are a few tips that may be of benefit during extended travel (table 1).
SPECIAL PRECAUTIONS FOR PEOPLE WITH DEEP VEIN THROMBOSIS
Second thrombosis — Patients being treated for venous thrombosis are at an increased risk for developing another blood clot, although this risk is significantly smaller when heparin or warfarin (Coumadin®) is used. The patient should watch for new leg pain, swelling, and/or redness. If these symptoms occur, the patient should speak to their healthcare provider or seek medical attention as soon as possible.
Other symptoms may indicate that a clot in the leg has broken off and traveled to the lung, causing a pulmonary embolism. These may include:
- New chest pain with difficulty breathing
- A rapid heart rate and/or a feeling of passing out
This complication may be life-threatening and requires immediate attention. Emergency medical services are available in most areas of the United States by calling 911.
Bleeding — Anticoagulants such as heparin and Coumadin® can have serious side effects and should be taken exactly as directed. If a dose is forgotten, the patient should call their provider or clinic for advice. The dose should not be changed to make up for missed doses. Patients should immediately report to the pharmacist or physician if the pill or tablet looks different than the previous bottle. Other precautions are necessary when taking Coumadin, which are outlined in a separate topic review. (See “Patient information: Warfarin (Coumadin®)”.)
Patients may bleed easily while taking anticoagulants. Bleeding may develop in many areas, such as the nose or gums, excessive menstrual bleeding, bleeding in the urine or feces, bleeding or excessive bruising in the skin, as well as vomiting material that is bright red or like coffee grounds. In some cases, bleeding can develop inside the body and not be noticed immediately. Bleeding inside the body can cause a person to feel faint, or have pain in the back or abdomen. A healthcare provider should be notified immediately if there is any sign of this problem.
Wear an alert tag — People who take warfarin should wear a bracelet, necklace, or similar alert tag at all times. If medical treatment is required and the person is too ill to explain their condition, the tag will alert responders about the patient’s use of warfarin and risk of excessive bleeding.
The alert tag should list the person’s medical conditions, as well as the name and phone number of an emergency contact. One device, Medic Alert®, provides a toll-free number that emergency medical workers can call to find out a person’s medical history, list of medications, family emergency contact numbers, and healthcare provider names and numbers.
Reduce the risk of bleeding — Some simple modifications can limit the risk of bleeding:
- Use a soft bristle toothbrush
- Floss with waxed floss rather than unwaxed floss
- Shave with an electric razor rather than a blade
- Take care when using scissors or knives
- Avoid potentially harmful activities (eg, contact sports)
- Do not take aspirin or other NSAIDS (eg, ibuprofen, Advil, Aleve, Motrin, Nuprin). Other nonprescription pain medications, such as acetaminophen, may be a safe alternative.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed every four months on our Web site (www.uptodate.com/patients).
Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient Level Information:
Patient information: Pulmonary embolism
Patient information: The nephrotic syndrome
Patient information: The antiphospholipid syndrome
Patient information: Warfarin (Coumadin®)
Professional Level Information:
Anticoagulation during pregnancy
Approach to the diagnosis and therapy of lower extremity deep vein thrombosis
Deep vein thrombosis and pulmonary embolism in pregnancy: Epidemiology, pathogenesis, and diagnosis
Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention
Deep vein thrombosis and pulmonary embolism in pregnancy: Treatment
Diagnosis of suspected deep vein thrombosis of the lower extremity
Etiology, clinical features, and diagnosis of cerebral venous thrombosis
Evaluation of the patient with established venous thrombosis
Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis
Hypercoagulable disorders associated with malignancy
Inferior vena cava filters
Low molecular weight heparin for venous thromboembolic disease
Management of anticoagulation before and after elective surgery
Management of inherited thrombophilia
Overview of the causes of venous thrombosis
Prevention of venous thromboembolic disease in medical patients
Prevention of venous thromboembolic disease in surgical patients
Therapeutic use of heparin and low molecular weight heparin
Therapeutic use of warfarin
Treatment of lower extremity deep vein thrombosis
The following organizations also provide reliable health information.
- National Library of Medicine
- National Heart, Lung, and Blood Institute
- American Heart Association
- Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:454S.
- Kelman CW, Kortt MA, Becker NG, et al. Deep vein thrombosis and air travel: record linkage study. BMJ 2003; 327:1072.
- Chee YL, Watson HG. Air travel and thrombosis. Br J Haematol 2005; 130:671.
- Martinelli I. Risk factors in venous thromboembolism. Thromb Haemost 2001; 86:395.
- Hyers TM. Venous thromboembolism. Am J Respir Crit Care Med 1999; 159:1.
- Qaseem A, Snow V, Barry P, et al. Current diagnosis of venous thromboembolism in primary care: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med 2007; 146:454.
- Segal JB, Streiff MB, Hofmann LV, et al. Management of venous thromboembolism: a systematic review for a practice guideline. Ann Intern Med 2007; 146:211.
- Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Fam Med 2007; 5:74.
- Blann AD, Lip GY. Venous thromboembolism. BMJ 2006; 332:215.