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Old 06-12-2008, 05:41 PM
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Default Disorder Magnifies Blood Clot Risk


When David Bloom, 39, went to Iraq in 2003 to cover the war for NBC News, his wife, Melanie, naturally feared for his safety. Would a bullet or a bomb claim him? A land mine? An ambush?
Instead it was a blood clot lodged in his lungs that ended his life. Ms. Bloom subsequently learned that her husband carried a genetic abnormality, factor V Leiden, that greatly increased his risk for developing blood clots.
Mr. Bloom had three other risk factors for clots: a long plane ride to Iraq, erratic eating habits that could have caused dehydration, and cramped sleeping space in Army vehicles. But had he not had this genetic quirk — or had he known about it and the higher risks it carried — he might have escaped his fate.
A Hidden Problem
Factor V Leiden (pronounced factor five) is the most common hereditary clotting disorder in the United States, present in 2 percent to 7 percent of Caucasians, less often in Hispanics and rarely in Asians and African-Americans.
The disorder accounts for 20 percent and to 40 percent of cases of deep vein thrombosis, or D.V.T., the clot that Mr. Bloom developed in his leg before it broke loose and traveled to his lungs, resulting in a pulmonary embolism that caused his death.
Factor V Leiden is more often than not a hidden disorder, until someone in a family — often someone like Mr. Bloom, who was athletic and healthy — develops a deep vein thrombosis or another unexpected clot. Because screening for this problem is not routine, factor V Leiden is usually not detected until several members of a family develop clots or one person develops a succession of clots.
Even then, a possible carrier of the gene defect may not be tested.
Dr. Rinah Shopnick, medical director of the Hemophilia and Thrombosis Center of Nevada, described the case of Ann, 20, who reported to the center about her doctors’ reactions to her family history. Ann told doctors that her otherwise healthy cousin had suffered a major heart attack in his 40s and was found to have factor V Leiden. Her grandmother died while pregnant, and her aunt, uncle and grandfather died of heart problems.
Ann reported that she had had blood pressure problems since age 8, and developed a serious blood pressure disorder during pregnancy and that her brother had just tested positive for the defect.
Yet she was advised by two doctors not to be tested, she said. The reasoning was that the disorder was rare, that she would have to pay for the test (it is not expensive) and that if she was found to carry the gene it could affect her ability to buy affordable life and health insurance. (Federal legislation has just been passed to protect against such discrimination.)
Inherited Risk
In someone with factor V Leiden, clots can arise in veins anywhere. The abnormality can increase the risk of heart attack, stroke, miscarriage, gallbladder dysfunction and toxemia of pregnancy. Clots are also more likely to develop after surgery and childbirth and in women taking oral contraceptives or estrogen therapy.
The disorder results from a mutation in the factor V gene that participates in forming clots in response to an injury, for example. Without two fully functional factor V genes, the body’s ability to put a brake on clot formation is inhibited.
Normally, a molecule called activated protein C, or APC, prevents clots from becoming too large by inactivating coagulation factor V. But factor V Leiden impairs this protein’s ability to suppress the coagulation factor because it is longer lasting and stickier.
A parent who carries the mutated gene has a 50 percent chance of passing it on to each child. Someone who inherits one mutated gene faces a five- to seven-fold increased risk of developing a serious and potentially life-threatening clot. Someone with two of the damaged genes has a 25- to 50-fold increased risk. Approximately one person in 5,000 among whites in the United States and Europe has two of the mutated genes.
Because the risk of suffering a clot is about one in 1,000 people a year in the general population, the increased risk associated with factor V Leiden is not to be taken lightly: 5 to 7 in 1,000 people each year for those with one mutant gene and 25 to 50 per 1,000 in those with two mutant genes. The risk is greatest in individuals who have more than one clotting defect, as well as in people who smoke or are overweight.
A Danish study of 9,253 adults found that in people who did not smoke, were not overweight and were younger than 40, the 10-year risk of clots and emboli was 1 percent in those with one mutated gene and 3 percent in those with two damaged genes. But the risk increased to 10 percent in people with one mutated gene and 51 percent in those with two abnormal genes if they smoked, were overweight and were older than 60.
Screening
Two blood tests can detect factor V Leiden. One, the APC resistance assay, is 95 percent accurate and could be used for screening. It measures the anticoagulant response to activated protein C. A definitive but more costly diagnosis, also performed on blood, can be made by genetic analysis of the factor V gene.
One or both tests is recommended for people with D.V.T., pulmonary embolism, premature stroke, repeated miscarriage, a family history of clots or a known factor V mutation in a blood relative. Thus, Mr. Bloom’s three daughters should be tested, because each has a 50 percent chance of carrying the defective gene.
For people with a personal or family history of clots, testing can help avert clotting complications when they undergo major surgery, are treated for cancer, anticipate pregnancy or plan to take oral contraceptives, estrogen therapy or a drug like tamoxifen.
In women with factor V Leiden, for example, treatment with an anticoagulant during pregnancy can reduce the risk of pregnancy loss. Women needing contraception might be wise to avoid birth control pills and instead choose a method that would not increase their risk of clots. And a person who is hospitalized or needs surgery can be treated with blood thinners and mechanical compression boots.
Though factor V Leiden alone does not seem to raise the risk of arterial clots, something as simple as daily therapy with low-dose aspirin may help prevent a heart attack or stroke in people with factor V Leiden if they have additional risk factors.
Preventive action is also important during long periods of immobilization, including long car and plane rides. Drinking plenty of water to prevent dehydration, avoiding alcohol, taking frequent walks and wearing elastic stockings can lower the risk of clots on such excursions.
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