**The Epidemiology of Venous Thromboembolism**

John A. Heit, M.D.

**From the Divisions of Cardiovascular Diseases (Section of Vascular
Diseases) and Hematology (Section of Hematology Research), Department of
Internal Medicine; and the Divisions of Hematopathology and Laboratory
Genetics, Department of Laboratory Medicine and Pathology; Mayo Clinic
and College of Medicine, Rochester, MN.**

**Short title: VTE Epi**

** Funded, in part, by grants from the National Institutes of Health
(HL-66216, HL-83141, HL-83797, U-195457, and AR-30582), and the Centers
for Disease Control and Prevention (TS-1255), U.S. Public Health
Service; and by Mayo Foundation.**

** Correspondence to: Dr. John A. Heit, Hematology Research, Stabile
660, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; Telephone:
(507)284-4634; Facsimile: (507)266-9302; e-mail: .**

**Word Count: 1,338**

**© 2006 Mayo Foundation**

**Introduction**

Deep vein thrombosis consists of one or more blood clots within the
inside ("deep") veins of the leg and pelvis. These clots may be as large
around as ones thumb and may be quite long, extending from below the
knee all the way up to above the groin. The most frequent symptoms of
deep vein thrombosis are swelling and pain of the lower leg. If the clot
becomes dislodged, it flows with the blood returning from the leg to the
heart. The heart pumps this blood to lungs where the blood clot becomes
lodged, obstructing the flow of blood through the lungs. This is called
pulmonary embolism, and the most frequent symptom is shortness of
breath. As one can imagine, a pulmonary embolism can be quite serious,
even fatal. The overall term for deep vein thrombosis and its
complication, pulmonary embolism, is venous thromboembolism.

The following discussion addresses several fundamental questions about
venous thromboembolism, such as how often does it occur and in whom does
it most often occur; can venous thromboembolism recur and if so, how
often; how often do people die from venous thromboembolism; for those
survive, what are the long-term complications and do they affect ones
quality of life; and what has happened to the occurrence of venous
thromboembolism over time? Together, these questions address what is
termed the "epidemiology" of venous thromboembolism, including the
incidence, survival, recurrence and complications of the disease.

**How often does venous thromboembolism occur, and in whom does it most
often occur?**

It's been difficult to determine just how many people actually develop
deep vein thrombosis and pulmonary embolism in the U.S. each year. Leg
swelling and pain, and shortness of breath, may be caused by many
diseases and are not specific for deep vein thrombosis and pulmonary
embolism, respectively. Often, a deep vein thrombosis may cause no
symptoms until it suddenly dislodges and travels to the lungs (now a
pulmonary embolism), leading to sudden death. Thus, many people have
venous thromboembolism that is unrecognized. Recent studies from several
investigators now show that among a group of 100,000 persons observed
for one year, about 120 will develop a first-lifetime venous
thromboembolism. Said a different way, the incidence of venous
thromboembolism is about 120 per 100,000 person-years.^1,2,3^ However,
the incidence varies markedly depending on an individual's age and sex.
For example, the incidence among persons that are 14 years of age or
younger is less than 1 per 100,000 person-years. The incidence begins to
increase dramatically around age 50, such for 85 year olds or older the
incidence approaches 1000 per 100,000.^1^ The incidence is higher among
women during childbearing years, while the incidence is higher among men
after age 50.^1^

The incidence of venous thromboembolism also varies by race. Compared to
whites, African-Americans have an incidence that is about 30% higher
while Asian- and Native-Americans have an incidence that is about 70%
lower; the incidence among Hispanics is intermediate between whites and
Asian-Americans.^4,5^ Based on this information, researchers have
estimated that over 300,000 US residents develop a first lifetime venous
thromboembolism each year.^6^

**How often does venous thromboembolism recur?**

About 30% of venous thromboembolism patients will develop a second
episode within the next 10 years.^7,8^ The risk of recurrence is
greatest within the first two years. However, the risk never falls to
zero; compared to persons who have never suffered a deep vein thrombosis
or pulmonary embolism, patients with one episode remain at higher risk
for developing one or more additional venous thromboembolism events for
the remainder of their lives.

**How often do people die from venous thromboembolism?**

Overall, about 30% of venous thromboembolism patients die within the
next three months.^9^ Compared to persons of similar age and sex,
survival after venous thromboembolism is worse than would be expected.
As indicated above, survival after pulmonary embolism is much worse than
after deep vein thrombosis alone; almost one-quarter of pulmonary
embolism patients die suddenly and without forewarning, and almost 40%
die within three months. Venous thromboembolism often affects persons
with other concurrent diseases that reduce survival. However, after
controlling for other common medical causes of death, pulmonary
independently reduces survival for up to three months.

**So, what is the total number of people who develop venous
thromboembolism in the US each year?**

Using a specially-developed computer model, researchers have
conservatively estimated that over 900,000 persons develop incident or
recurrent, fatal or non-fatal venous thromboembolism each year.^10^ This
number is much larger than previously thought. Of even greater concern,
almost one-third of these persons developed fatal venous
thromboembolism. Clearly, venous thromboembolism is a major national
health problem of a magnitude similar to other thrombotic diseases, such
as heart attack and stroke. For example, the total number of venous
thromboembolism events each year exceeds the estimated number of heart
attacks (n=865,000) and of strokes (n=700,000). Moreover, the number of
venous thromboembolism-related deaths exceeds the number of deaths
related to heart attack (n=171,000) and stroke (n=158,000). Furthermore,
the number of deaths due to pulmonary embolism each year is predicted to
increase. As discussed above, the incidence of venous thromboembolism
increases dramatically with age, and the relative proportion of those
events that are pulmonary embolism (with its associated poor survival)
also increases with age.^1^ So, as the average US population age
increases, the total number of pulmonary embolism events (and associated
deaths) occurring each year will increase.

**Among those who survive, what are the long-term complications of
venous thromboembolism, and how do they affect quality of life?**

Recall that blood in veins is flowing back to the heart. However, while
in the standing position, gravity tends to "pull" the blood in the wrong
direction. This tendency toward reversal of blood flow is prevented by
venous valves located periodically throughout the course of the deep
veins of the leg. A deep vein thrombosis may destroy one or more of
these valves as well as cause persistent complete or partial obstruction
of veins. The long-term consequence of this venous valvular dysfunction
and/or venous outflow obstruction is a symptom complex of leg pain and
swelling in the standing position. For those most severely affected, the
skin at the inside ankle becomes thickened and darkened, and is prone to
recurrent skin breakdown and painful ulcers that are difficult to heal.
This symptom complex has been termed "venous stasis syndrome". About 12%
of patients with venous stasis syndrome have had a previous deep vein
thrombosis^11^, and about 30% of deep vein thrombosis will subsequently
develop venous stasis syndrome (often called post thrombotic syndrome)
within the next 10-20 years.^8,12,13^ Almost 400,000 people suffer from
post thrombotic syndrome in the US.^10^ Recent research shows that
patients with postthrombotic syndrome have a significant reduction in
quality of life that is of a similar magnitude to patients with chronic
heart, lung or arthritic disease.^14,15^

Our bodies have an internal ability of dissolve ("lyse") blood clots.
Hence, for most patients with pulmonary embolism, the blood clot in the
lungs lyses and blood flow is restored to normal. However, for unclear
reasons, some pulmonary embolism patients fail to completely lyse these
lung blood clots. This leads to another complication of venous
thromboembolism, termed chronic thromboembolic pulmonary hypertension
(**CTEPH**). These patients often are severely impaired due chronic
shortness of breath and heart failure. Fortunately, this complication is
relatively rare, with an incidence of about 6.5 per million person-years
or about 1400 first lifetime cases of CTEPH each year.^6,16^
Nevertheless, over 4000 people are estimated to have CTEPH in the
US.^10^

**What has happened to the occurrence of venous thromboembolism over
time?**

As can be seen from the discussion above, to improve survival, prevent
recurrence and avoid the complications of venous thromboembolism, the
occurrence of the disease must be reduced. Unfortunately, the occurrence
(or "incidence") of this disease has not changed over recent time.^1,6^
Compared to the 10-year period, 1981-1990, when the incidence of venous
thromboembolism was 116 per 100,000 person-years, the incidence for the
subsequent 9-year period, 1991-1999 is virtually unchanged at 118 per
100,000. Clearly, more effort should be directed at reducing the
incidence of this disease.

**References**

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    Melton, III LJ. Trends in the incidence of deep vein thrombosis and
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2.  **Heit JA, Melton LJ III, Lohse CM, Petterson TM, Silverstein MD,
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16. Dunn WF, Heit JA, Farmer SA, Petterson TM, Ballman KV. The incidence
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