Deep Vein Thrombosis

Introduction

You have been resting at home after having surgery a week ago. Suddenly, you notice one of your calves is bright red, swollen, and warm. It hurts when you touch it. These symptoms could mean that you have deep vein thrombosis (DVT). Each year, thousands of people develop DVT, which can have serious complications.

What is it?

Deep vein thrombosis (DVT) is the term used to describe blood clots (also called thrombi) that form in the veins, usually in the lower legs. These clots can grow in size and interfere with blood flow in the legs; and sometimes the clots break loose and travel to the lungs, brain, heart, or other areas of the body. When the clots lodge in other organs or tissues, they can block blood flow, and cause serious damage to these organs. As many as 50% of patients with DVT experience damage to their lungs caused by a clot. This condition is commonly known as a pulmonary embolism (PE).

What causes it?

Deep vein thrombosis (DVT) is caused by decreased blood flow in the veins, injury to the veins, and increased clotting ability of the blood. Many different factors can contribute to the causes of DVT (see Risk Factors).

Who has it?

An estimated 2 million people in the United States develop DVT each year; of those 600,000 are hospitalized and approximately 60,000 die. The incidence of DVT doubles in each decade of life over the age of 50. African Americans appear to be at somewhat higher risk of DVT. Hispanic Americans are thought to be somewhat protected from developing DVT, while Asian Americans and Pacific Islanders appear to have a strikingly lower incidence of DVT.

What are the risk factors?

Conditions that cause slowing of blood flow or thickening of the blood place individuals at highest risk for deep vein thrombosis (DVT). You may be at risk to develop DVT if you have any of the following:

Trauma

  • Surgery on the legs, hips, or knees
  • Surgery on the pelvis or abdominal organs
  • Badly broken leg bones
  • Spinal cord injury
Hereditary Factors
  • Disorders of blood clotting factors (Protein C, Protein S, Antithrombin III, Fibrinogen, Leiden factor V)
  • Polycythemia vera (increased production of red blood cells, white blood cells and platelets by the bone marrow)
  • Sickle cell anemia (inherited disease resulting in abnormally shaped red blood cells)
Diseases
  • Cancer (chemotherapy or radiation can also increase your risk)
  • Heart disease
  • Lung disease
  • Inflammatory bowel disease
  • Systemic lupus erythematosus
  • Bone marrow diseases (for example, granulocytic leukemia)
  • Varicose veins
  • Stroke or paralysis
Other
  • Age (risk increases for persons aged 40 years and older)
  • Immobility (for example, chronic bed rest) or paralysis
  • Pregnancy and up to 1 year after childbirth
  • Estrogen use (birth control or hormone replacement therapy)
  • History of previous DVT or pulmonary embolism
  • History of varicose veins
  • Kidney transplant
  • Obesity
  • Spleen removal
  • Chronic venous insufficiency (decreased blood flow)

What are the symptoms?

While it is common to not experience any symptoms at all, some people may experience any of the following symptoms of a DVT:

  • Leg pain, usually in only one leg
  • Leg tenderness, usually in only one leg
  • Swelling (edema), usually in only one leg
  • Increased warmth, usually in only one leg
  • Changes in skin color (red or bluish), usually in only one leg
  • Joint pain
  • Sharp pain when the foot is bent upward
Laboratory tests:

The following lab tests are commonly performed to help diagnose a DVT:

  • Ultrasound (used to detect DVT)
  • D-dimer (used to rule out a DVT)
  • Chest X-ray (used to detect clots in lungs)
  • Antiphospholipid antibodies (indicators in the blood that a person has an increased risk of DVT)
  • Venography (the most accurate test for detecting a clot in the leg)

How is it treated?

Deep vein thrombosis (DVT) is usually treated with anticoagulants such as heparin and warfarin--medications that prevent the blood from clotting (coagulating) any further. This allows the body's natural defenses to break down existing clots gradually. Occasionally, drugs that actually dissolve clots are used. These "clot busters" are not commonly used for DVT, however, unless a serious risk of life-threatening complications exists.

Injectable and oral anticoagulants are used for treatment. The injectable medication is usually given along with the oral medication during the first week or until the oral medication becomes fully effective. The oral medication is then continued for prevention of a repeat DVT for 3 to 6 months for most patients. Sometimes it may be necessary to remain on the oral medication longer. This is dependent on your previous history of a DVT episode or continuous risk factors such as cancer or hereditary diseases.

When taking the oral anticoagulant, it is important to note that your doctor will require very careful monitoring of the medication, and it may be necessary to change your dose periodically. Your doctor or pharmacist will use a blood test that measures your International Normalized Ratio (INR) to adjust your dose. It is important to take the medication exactly as directed by your doctor or pharmacist to ensure that you are not at risk to develop another DVT or increased bleeding.

INR Testing

Patients who take warfarin should have their International Normalized Ratio (INR) monitored frequently throughout the duration of their therapy. An INR indirectly indicates the amount of time it takes for your blood to clot. There are specific INR values that are optimal for treatment of DVT. Your doctor can tell you what your specific goal is.

  • For prevention and treatment of a current DVT, an INR value in the range of 2 to 3 with a goal of 2.5 is desired.

  • If a person has other medical conditions (for example, a mechanical heart valve), the INR value in the range of 2.5 to 3.5, with a goal of 3.0 is desired.

It is extremely important to have your INR regularly monitored for the following reasons. Too much warfarin could potentially increase your INR and as a result, put you at risk for excess bleeding. On the other hand, too little warfarin could potentially decrease your INR and put you at risk for developing a clot.

Make sure you have your INR initially monitored twice during the first week you begin treatment. Then once your INR has stabilized, have your INR monitored every 4-6 weeks or more often (as recommended by your doctor or pharmacist) if the INR is not within goal range.

Dietary Considerations

It is important to eat a normal, well-balanced diet everyday. The amount of vitamin K in your body affects the way warfarin works; unusual and/or inconsistent consumption of foods with a high amount of vitamin K may affect the safety and effectiveness of warfarin. Foods with a high amount of vitamin K include liver meat, broccoli, spinach, cauliflower, cabbage, brussel sprouts, kale, and other dark green leafy vegetables. Because of this fact, strictly vegetarian diets that consist of high amounts of vitamin K containing foods should be avoided. If you use any dietary supplements or vitamin products, check with your doctor or pharmacist to make sure they do not contain high amounts of vitamin K.

Avoid drinking alcohol while taking warfarin because it may increase the risk of stomach bleeding.

What to Watch For

Because warfarin can cause bleeding if not properly monitored, notify your doctor as soon as possible if you experience any of the following:

  • Excessive nose bleeds
  • Excessive bleeding from cuts or scrapes
  • Excessive bleeding from your gums
  • Discoloration of your stools (dark and tarry) or bright red blood in stools
  • Heavy menstrual bleeding
  • Unusual or easy bruising
  • Persistent nausea or vomiting
  • Stomach pain
  • Yellowing of eyes/skin
  • Persistent, severe back pain

Although unlikely, immediately notify your doctor if you experience a severe allergic reaction to warfarin. Symptoms of an allergic reaction include rash, itching, swelling, severe dizziness, and trouble breathing.

Drug Interactions

Due to the fact that warfarin interacts with many commonly used medications and medication ingredients, it is important that you inform your doctor or pharmacist about any new prescription and non-prescription medications, supplements, vitamins, and herbals that you may be taking.

Some common interacting drugs include:

  • acetaminophen
  • medications that dissolve blood clots
  • medications that lower cholesterol
  • alcohol
  • allopurinol
  • amiodarone
  • antibiotics or medicines for treating bacterial, fungal or viral infections
  • antiinflammatory drugs, NSAIDs, such as ibuprofen
  • aprepitant
  • aspirin
  • azathioprine
  • barbiturate medicines for inducing sleep or treating seizures
  • bosentan
  • cimetidine
  • cyclosporine
  • disulfiram
  • female hormones, including contraceptive or birth control pills
  • fish oil (omega-3 fatty acids) supplements
  • herbal products such as danshen, garlic, ginkgo, ginseng, green tea, or kava kava
  • influenza virus vaccine
  • male hormones
  • medicines for some types of cancer
  • certain medicines for heart rhythm problems
  • certain medicines for high blood pressure
  • quinidine, quinine
  • seizure or epilepsy medicine such as carbamazepine, phenytoin, and valproic acid
  • testolactone
  • thyroid medicine
  • tolterodine
  • vitamin K (including vitamin, mineral, and food supplements that contain vitamin K)

You can also check if the medication you are currently taking interacts with warfarin by using our drug interaction checker.

Importance of Compliance

It is extremely important that you take warfarin exactly as prescribed by your physician. Any unmonitored changes in your warfarin treatment could result in serious bleeding or clotting complications.

It is best to take warfarin around the same time everyday. If you miss a dose of warfarin at the scheduled time, take the dose as soon as you remember if its the same day. If you miss a dose and do not remember until the next day, do not double the dose to make up for the missed dose. Be sure to report any missed doses or mistakes in taking doses to your healthcare provider.

Finally, be sure you do not run out of your warfarin tablets. Get your prescription refilled on time and alert your doctor if you need additional refills on your warfarin prescription.

Helping Yourself

Although effective medications to treat DVT are available, doing whatever you can to prevent a clot is especially important if you are at risk. This can be accomplished by modifying as many of your risk factors as possible. The following are good ways to decrease your risk:

  • Lose weight
  • Stop smoking
  • Exercise moderately and regularly
  • Keep your blood pressure under control
  • Keep your cholesterol levels in a healthy range
  • Maintain an active lifestyle
  • Resume activity as soon as possible after surgery (follow the advice of your doctor)
  • Elevate your feet above your heart when you are immobile
  • Wear support stockings or use other products that promote circulation such as a bed wedge or leg wedge
  • Keep Moving! If you must stay seated for long periods of time, move your feet regularly.

What is on the horizon?

Thrombolytic agents are injected slowly into the bloodstream to dissolve dangerous clots rapidly. They are usually reserved for life-threatening pulmonary embolism (blood clot in the lung) since, they have a greater risk of causing serious bleeding. They are given under close supervision in hospitals. However, studies are now investigating the effectiveness and safety of these agents when they are injected directly into blood clots.

An oral direct thrombin inhibitor, dabigatran, is currently being investigated in Stage III clinical trials and has been found to be as effective as enoxaparin for prevention of DVT when taken for one month after total hip replacement surgery. Although the researchers in this study did not find a difference in major bleeding (a common side effect of these medications) between the dabigatran and enoxaparin groups, larger studies will be done in the future to further assess this risk. The only other oral anticoagulant available today is warfarin, which requires extensive monitoring through regular blood tests. Dabigatran has not yet been approved by the FDA, but if future studies continue to find positive results it could become a very important drug in the prevention and possibly treatment of DVTs.

Therapies such as low molecular weight heparin used to prevent DVTs have also gained the interest of many healthcare providers. It is believed that measures used to prevent a DVT after neurosurgery may have a significant effect on decreasing the rate of death after surgery. More clinical studies are needed at this point to determine the use of preventative treatments.

Idraparinux (a Factor Xa Inhibitor) is a new pentassacharide that has been found in one study to have similar efficacy as standard therapy (heparin or low molecular weight heparin plus warfarin) in treating DVT, but was less efficacious in patients with pulmonary embolism (PE). Idraparinux is similar to fondaparinux but lasts much longer in the body, which allows it to be given as a weekly injection instead of daily or twice daily. But the fact that it did not show effectiveness against PE may limit its use because the other injectable anticoagulants have similar efficacy for both DVT and PE.

Rivaroxaban (a Factor Xa Inhibitor) is also currently being studied for prevention and treatment of DVT. It is another oral anticoagulant and is in the beginning of Phase III clinical trials, mainly being studied for prevention of DVT after total knee and hip replacement surgeries. Neither of these drugs has been approved by the FDA yet. However, if they are found to be effective in the clinical trials, they may gain FDA approval in the next few years.

References

Haines ST, Racine E, Zeolla M. Venous Thrombosis. In: Dipiro JT, Talbert RL, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. McGraw-Hill. 6th ed. 2005:357-414.

Holbrook A, Labiris R, Crowther M. Systematic Overview of Warfarin and Its Drug and Food Interactions. Archives of Internal Medicine. 2005;165:1095-1106

Medlineplus: Health Information. Deep Vein Thrombosis. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000156.htm. Accessed May 2005, June 8, 2006, March 28, 2007, and March 24, 2008.

Neurosurgical Focus. Volume 18, Issue 4. Prophylaxis for Deep Venous Thrombosis in Neurosurgery: A Review of the Literature. Available at Medscape: http://www.medscape.com/viewarticle/491476?src=search. Accessed May 2005, June 8, 2006, March 28, 2007, and March 25, 2008.

Chang R, Horne MK 3rd, Mayo DJ, Doppman JL. Pulse-spray treatment of subclavian and jugular venous thrombi with recombinant tissue plasminogen activator. Journal of Vascular and Interventional Radiology. 1996;7:845-851.

Elliot MS, Immelman EJ, Jeffery P, et al. A comparative randomized trial of heparin versus streptokinase in the treatment of acute proximal vein thrombosis: an interim report of a prospective trial. British Journal of Surgery. 1979;66:838-843.

van Gogh Investigators, Buller HR, Cohen AT, et al. Idraparinux versus standard therapy for venous thromboembolic disease. New England Journal of Medicine. 2007 Sep 13;357(11):1094-104.

Eriksson B, Dahl OE, Rosencher N, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomized, double-blind, non-inferiority trial. The Lancet. 2007 Sep 15;370:949-956.

Deep Vein Thrombosis Health Condition Last Updated: March 2008

Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.

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