Blood, 1 July 2001, Vol. 98, No. 1, pp. 20-20
PERSPECTIVE
Genetic hypercoagulability: screening should be an informed
choice
David Green
From the Division of Hematology/Oncology, Department of
Medicine, Northwestern University Medical School, Chicago, IL.
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Article |
Recently, I received an e-mail from a frantic woman
in another state. She had just learned that her husband's brother had a thrombosis associated with an inherited tendency to
hypercoagulability. Her 12-year-old daughter was about to undergo
hernia surgery. She asked whether the operation should be canceled and
her daughter have genetic testing.
The brother-in-law was heterozygous for the prothrombin gene mutation
(prothrombin G20210A). This mutation occurs in up to 3% of Caucasian
Americans.1 The simplest response to the woman's query
would be to suggest postponement of the surgery and to have the
daughter tested. If the test were positive, a visit to a hematology consultant would be recommended. Although this is the simplest course,
I do not believe it is the right approach.
Proponents of screening observe that knowledge of the presence of a
gene mutation may enable affected individuals to better protect
themselves against thromboembolism by taking various measures. These
measures might include avoiding known risk factors such as prolonged
sitting or standing during travel, as well as not using oral
contraceptive agents or other drugs considered thrombogenic. In
addition, these persons may educate themselves about the signs and
symptoms of venous thromboembolism so that earlier recognition of an
event might occur. Furthermore, they might inform their healthcare
providers about the presence of the mutation, which might lead to more
intensive thromboprophylaxis during periods when the person is at risk
and to earlier diagnosis of thromboembolic events. However, identifying
a specific mutation is not required for introducing these measures.
Simply knowing that a relative has a thrombotic disorder may give
sufficient warning that there is a potential risk of thrombosis. Family
members could communicate this information to their healthcare
providers and inform themselves about the risks of thrombosis.
What is the downside of screening? Yan et al2 listed a
number of reasons for caution. First, they noted that identification of
a gene mutation may lead to insurance and employment discrimination as
well as loss of privacy. Second, testing in the absence of effective
interventions raises ethical concerns; analogy is made to screening for
sickle cell trait.3 Affected individuals with thrombophilic mutations are at risk for thrombosis and there is no
simple intervention that changes that fact. Third, the mutations are
usually associated with a late onset of symptoms. Thrombosis in
childhood is rare; factor V Leiden, prothrombin 20210 mutation, and
heterozygosity for mutations in the protein C, protein S, and
antithrombin genes are almost never the only cause.4 When clinical events occur in persons with these mutations, they are usually
after puberty and in association with other risk factors. Fourth,
learning of the presence of a mutation may provoke considerable anxiety
and may affect important life decisions. For example, female family
members found to have thrombophilia genes would probably be unable to
obtain prescriptions for oral contraceptives or estrogens. If the gene
mutation was not explicitly recognized, a woman's physician might
conclude that, in her specific case, the benefit of hormonal use
outweighed the risk of thrombosis (3.3 in the case of carriers of
factor V Leiden5). Finally, because of technologic
problems, testing may be incomplete or inaccurate.
Ultimately, decisions about screening for mutations should be made by
family members and their physicians. Persons for whom testing is
contemplated should be informed about the risks and benefits of
screening. They should be told that, even if a mutation is discovered,
no more than 5% of persons with the most common mutations, those
involving factor V and prothrombin, will ever experience an
event.6,7 In addition, no major effect of factor V Leiden
on life expectancy may be anticipated.8 There would appear
to be very few instances in which it is justified to screen children;
such testing should be deferred until the child is past puberty and
better able to decide whether the benefits of testing outweigh the
risks. For other family members, thorough counseling is required so
that each person can make a fully informed choice.
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Footnotes |
Submitted November 15, 2000; accepted March 1, 2001.
Reprints: David Green, 345 E Superior St, Rm 1407, Chicago, IL 60611; e-mail: d-green{at}northwestern.edu.
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References |
1.
Rosendaal FR, Doggen CJM, Zivelin A, et al.
Geographic distribution of the 20210 G to A prothrombin variant.
Thromb Haemost.
1998;79:706-708[Medline]
[Order article via Infotrieve].
2.
Yan H, Kinzler KW, Vogelstein B.
Genetic testing
present and future.
Science.
2000;289:1890-1892[Free Full Text].
3.
Beutler E, Boggs DR, Heller P, Maurer A, Motulsky AG, Sheehy TW.
Hazards of indiscriminate screening for sickling.
N Engl J Med.
1971;285:1485-1486.
4.
Rosendaal FR.
Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis.
Thromb Haemost.
1997;78:1-6[Medline]
[Order article via Infotrieve].
5.
Middeldorp S, Henkens CMA, Koopman MMW, et al.
The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis.
Ann Intern Med.
1998;128:15-20[Abstract/Free Full Text].
6.
Rodeghiero F, Tosetto A.
Activated protein C resistance and factor V Leiden mutation are independent risk factors for venous thromboembolism.
Ann Intern Med.
1999;130:643-650[Abstract/Free Full Text].
7.
Simioni P, Prandoni P, Girolami A.
Low rate of venous thromboembolism in asymptomatic relatives of probands with factor V Leiden mutation [letter].
Ann Intern Med.
1999;130:538[Free Full Text].
8.
Hille ETM, Westendorp GJ, Vandenbroucke JP, Rosendaal FR.
Mortality and causes of death in families with the factor V Leiden mutation (resistance to activated protein C).
Blood.
1997;89:1963-1967[Abstract/Free Full Text].
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