Deep vein thrombosis (DVT), sometimes called “economy class syndrome” is the formation of a blood clot in a vein deep within the body, usually in the legs.  Not only can DVT be painful, but it can also lead to a potentially fatal condition called pulmonary embolism if the clot breaks free and travels through the circulatory system to the lungs.

In addition to environmental factors, there are genetic variations that can raise a person’s chances of having DVT.  But providing genetic testing to everyone is not feasible, leading researchers from the Leiden University Medical Center in the Netherlands to question whether a family history of DVT could also be of value as a risk indicator.

The researchers looked at records and family histories of 3,764 people – 1,605 who had had DVT and 2,159 who had not.  Their results, published online this week in the Archives of Internal Medicine, show that in people with no environmental or genetic risk factors, having a first-degree relative (parentor sibling) with DVT increased the odds of having a first episode of DVT by 2.5 times.  This was about the same as the increase in odds (2.3 times) caused by genetic risk factors in people with no family history or environmental risk factors.

(The researchers considered several genetic risk factors, including the factor V Leiden and prothrombin variations reported in the 23andMe Venous Thromboembolism Clinical Report. A table summarizing the results of the current study is included at the end of this post.)

Only 29.7% of people with family history of DVT carried a known genetic risk factor, but a family history was more common in DVT patients than controls with similar known genetic and environmental risk factors.  This suggests that there are unknown, probably genetic, factors at work.  The researchers say that unknown genetic factors probably have small effects that contribute to DVT only when other, larger risk factors are present, such as the factor V Leiden genetic variation or an environmental risk factor such as surgery, immobilization or oral contraceptive use.

Based on the fact that a positive family history increases the risk of DVT to about the same degree as known genetic risk factors, and the fact that most people with a family history of DVT don’t actually carry a known genetic risk factor, the researchers conclude that genetic testing for variations associated with DVT is of little additional value compared to collecting family history alone.

However, while a cost-effectiveness argument might be made, the authors’ own data shows that known genetic risk factors substantially increase the odds of DVT whether or not a person has a family history of the condition.  A family history of DVT or a known genetic risk factor alone increases the odds of DVT by about two and a half times, but the presence of both increases the odds by 6.3 times.  The presence of an environmental risk factor raises the odds of DVT about nine and half times.  Add in a positive family history and the odds go up to more than 16 times those of someone who lacks known risk factors (both genetic and environmental) as well as a family history of DVT.  But in those unlucky enough to have a family history of DVT, an environmental risk factor and a known genetic risk factor, the odds of DVT are increased a whopping 64 times.


Notes on the results table:

• Odds are given relative to someone with a negative family history and no known risk factors for DVT.
• A family history of DVT is the presence of the condition in any parent, brother or sister.
• Environmental risk factors considered were surgery, injury, immobilization and pregnancy or delivery within three months of the study, use of oral contraceptive or hormone therapy at the time of the study, and cancer diagnosis within five years before or within six months after the start of the study.
• Genetic risk factors considered were the factor V Leiden variation, the prothrombin 20210A variation, and low levels of antithrombin, protein C or protein S.

ShareThis

This Monday acting Surgeon General Steven K. Galson issued a Call to Action to reduce the number of people in the United States affected by two serious blood clotting conditions: deep vein thrombosis and pulmonary embolism.

Deep vein thrombosis (DVT), sometimes called “economy class syndrome” is the formation of a blood clot in a vein deep within the body, usually in the legs. Pulmonary embolism (PE) occurs if the clot breaks free and travels through the circulatory system to the lungs. Together these two conditions affect an estimated 350,000 to 600,000 Americans each year and contribute to at least 100,000 deaths.

“Deep vein thrombosis and pulmonary embolisms are often ’silent’ conditions — they can occur suddenly and without symptoms,” Galson said in a statement. “But we have made a lot of progress in understanding how these disorders develop and how to prevent, diagnose, and treat them. It’s time to put this knowledge into action.”

Researchers have found that DVT and PE usually develop in response to a triggering event – being hospitalized or confined to bed rest, having major surgery, suffering a trauma, or traveling for several hours — in people who either have an inherited predisposition to blood clotting disorders or another risk factor.

23andMe customers have access to their data for the two most common genetic risk factors for DVT and PE (collectively known as Venous Thromboembolism).

Having the riskier version of one or both of the SNPs 23andMe reports data for (Factor V Leiden and Prothrombin 20210) significantly increases the risk of developing DVT or PE. An estimated 15 to 20 percent of DVT/PE patients have the Factor V Leiden mutation, while 6 percent have the Prothrombin 20210 mutation.

The average risk of DVT/PE in people between the ages of 40 and 59 (anyone can be afflicted, but risk does increase with age) is 2.5%. But in those people in this age group who inherit a copy of the Factor V Leiden mutation, the risk jumps to 11%. Having one copy of the Prothrombin 20210 mutation raises the risk to 8.8%. In the unlucky few who have one copy of each of these mutations, the risk is a 32%. And in the extremely rare case that someone inherits two copies of both mutations, the risk of DVT/PE is 69%.

(This information applies only to those with European ancestry. Average risk numbers are different for other groups, and the genetic risk factors discussed here are not usually found in people with African or Asian ancestry.)

Other risk factors for DVT and PE include being overweight or obese, cancer and its treatment, pregnancy and childbirth, use of hormones for birth control or menopause, and smoking.

“We want to increase the awareness and knowledge of these potentially deadly conditions and encourage patients and health care providers to take the steps to prevent them,” Galson said.

For more information:

• Surgeon General’s Fact Sheet on Deep Vein Thrombosis and Pulmonary Embolism
• The Coalition to Prevent Deep-Vein Thrombosis
• Patient and Provider Guides from the Agency for Healthcare Research and Quality (also available in Spanish)

ShareThis