J Thromb Thrombolysis (2008) 25:6–9
DOI 10.1007/s11239-007-0056-2
Genetic counseling for inherited thrombophilias
Elizabeth A. Varga
Published online: 19 October 2007
Springer Science+Business Media, LLC 2007
Abstract Genetic testing for inherited thrombophilia, Introduction
including mutation analysis for factor V Leiden and pro-
thrombin G20210A, is commonly performed. Yet, tests for Genetic tests for inherited hypercoagulability, including
inherited thrombophilia are frequently ordered inappropri- mutation analysis for factor V Leiden and prothrombin
ately, and without proper counseling about the risks, G20210A, are the two most frequently ordered molecular
benefits and limitations of testing. Genetic counselors are genetic tests in the United States [1]. Yet, there is still con-
uniquely trained to help people understand and adapt to siderable controversy regarding appropriate indications for
medical, psychological and familial implications of genetic thrombophilia testing, in part because testing may have
contributions to disease. In the context of thrombophilia, limited clinical utility. Consensus statements by the Amer-
genetic counselors may serve as a resource to other clini- ican College of Medical Genetics and the College of
cians to: (a) identify individuals and families at increased American Pathologists have provided a framework for cli-
risk for inherited thrombophilia, (b) offer and explain nicians regarding appropriate indications for thrombophilia
testing to patients and families, as appropriate, (c) facilitate testing [2–4]. However, discrepancies between these
patient-focused decision-making and informed consent guidelines do exist, as do ‘‘gray’’ areas where a patient may
prior to testing, (d) interpret test results, (e) explain or may not fit testing criteria. Due to these complexities,
inheritance patterns and discuss implications of thrombo- clinicians are often encouraged to discuss the advantages and
philia for family members and (f) provide education and disadvantages of testing with patients, so that individualized
support resources. This article will provide insight into the decisions can be made. Genetic counselors, who are uniquely
training and roles of genetic counselors, review indications trained to help people understand and adapt to medical,
for thrombophilia testing, and highlight specific issues psychological and familial implications of genetic contri-
related to genetic testing, including genetic discrimination butions to disease, can assist clinicians with this process.
concerns.
Keywords Genetic counseling Thrombophilia Who are genetic counselors?
Factor V Leiden Prothrombin
Genetic counselors are health professionals with special-
ized graduate degrees (typically a Master in Science in
genetic counseling or medical genetics) and experience in
the areas of medical genetics and counseling. Graduates
from accredited training programs are certified by the
American Board of Genetic Counseling (ABGC). Most
E. A. Varga (&) often, genetic counselors are employed by University or
Division of Molecular and Human Genetics, Columbus
private medical centers, but increasingly, counselors may
Children’s Research Institute, 700 Children’s Dr., Wexner 4,
Columbus, OH 43205, USA also work for public health agencies, industry, laboratories
e-mail: vargae@[Link]; eavarga@[Link] or at educational institutions [5].
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Genetic counseling—inherited thrombophilias 7
What happens at a genetic counseling session? thrombosis and/or thrombophilia. First, genetic counselors
may help identify individuals and families who are at
In the medical setting, genetic counselors are responsible increased risk to have hereditary thrombophilia by thor-
for providing clear and comprehensive information about oughly reviewing patient and family histories. When
any medical condition that may have a genetic component. appropriate, genetic counselors can offer and explain
The key components of a genetic counseling session genetic testing to patients and families. The limitations of
include: contracting (or establishing rapport); obtaining a genetic testing and how testing may or may not impact
medical history; constructing a 3–4 generation pedigree; management, as well as the potential for false reassurance,
performing a risk assessment; reviewing genetic concepts may also be explored. Furthermore, any concerns about
and explaining genetic testing and inheritance; discussion genetic discrimination, in the workplace or by insurers,
of implications of testing as well as advantages and dis- may be addressed.
advantages; and providing support and resources for the
individual and family as appropriate. Follow-up visits
typically include a discussion of test results and their Exploring the family history
implications for management (for the individual and
family), and psychosocial counseling and support. Exploring the family history with clients may serve a dual
purpose. Facts and information are obtained for risk
assessment purposes, but performing the intake also creates
The need for genetic counseling
the opportunity to explore family relationships, miscon-
ceptions, fears or anxieties. Often, the client’s
Is genetic counseling required for all patients prior to
misconceptions about inheritance (i.e. skipping genera-
thrombophilia testing? A recent study shed light on this
tions; males or females only being affected) or disease risk
issue. Their findings suggest that not all patient’s find
(i.e. everyone in my family will be affected), can be
genetic counseling necessary, but that it may be perceived
explored and addressed during this time.
as beneficial in some select sub-populations. Saukko et al.
Genetic counselors typically construct at least a 3-gen-
(2006) found that genetic counseling may be particularly
eration pedigree. A history of venous thromboembolism
important for (a) less informed patients who indicate that
(VTE) in the individual or his/her relatives, a history of
they only have a vague understanding of thrombosis or
pregnancy losses (recurrent, early or late), pregnancy
thrombophilia and its implications prior to testing, (b) those
complications (such as preeclampsia, placental abruption,
who are more worried about the testing, and c) those at
and preterm delivery and intrauterine growth restriction)
higher-risk for thrombosis or thrombophilia due to a strong
and a history of stroke and heart attack at young ages are
family history [6].
indicative of hereditary thrombophilia in the individual or
Studies have demonstrated that testing positive for
family. All health care practitioners should note, however,
inherited thrombophilia has the potential to influence daily
that the sensitivity of family history is highly dependent on
life by inducing concerns (about the need for treatment,
the reliability of the information and may range from 27–
lifestyle choices), feelings of stigmatization, distress and
49% [10, 11]. Therefore, verification of history through
confusion [7]. In another study, 43% of individuals with
medical documentation is essential.
factor V Leiden reported increased worry after learning of
The personal and family history may help to assess the
test results [8]. Increased anxiety may be due, in part, to
likelihood of a genetic thrombophilia in the individual or
overestimation of personal risk. In the case of factor V
family. Up to one-third of unselected patients with VTE
Leiden, one survey showed that at least 31% of patients
and more than 50% of patients with familial thrombosis
overestimate the risk of thromboembolism associated with
will have an identifiable thrombophilia [12]. Familial VTE
a positive test result [8]. Providing information pre- and
may be indicative of the co-inheritance of two or more
post-testing can be helpful in reducing distress and
thrombophilias [13]. The likelihood of identifying inherited
improving knowledge [7–9]. Therefore, it is important that
thrombophilia may also be higher in certain clinical situ-
adequate information and support be provided to those
ations, as discussed in latter sections of this article. The
undergoing testing and receiving test results—especially in
construction of a pedigree may help identify the most
those with increased worry.
appropriate candidate for evaluation, since it is most
helpful to begin thrombophilia testing in the person who
Genetic counselors and thrombophilia counseling has been clinically affected or is known to be at 50% risk
(i.e. have an affected parent or sibling). Testing appropriate
Genetic counselors may play a number of important roles individuals in the family can also avoid unnecessary test-
in the evaluation of individuals and families affected by ing; for example, knowing a thrombophilia is present in a
123
8 E. A. Varga
paternal aunt, it is unnecessary to test 3 nieces if their However, both agree that the implications of testing for the
father is negative. patient’s medical management, the familial nature of test
results, issues of confidentiality, and insurance ramifica-
tions, be discussed. A more thorough discussion of these
When should testing for thrombophilia be offered? issues should be undertaken with asymptomatic individuals
[19].
Consensus is emerging that genetic testing for thrombo- Concerns about confidentiality and insurance discrimi-
philia should be offered in certain situations. Both the nation are frequently raised in the context of genetic
American College of Medical Genetics (ACMG) and the testing. It is important that practitioners be able to answer
College of American Pathologists (CAP) agree that testing questions related to these topics, although this is no easy
for inherited thrombophilia should be offered to: individ- task, since protections related to genetic discrimination are
uals with venous thromboembolism (VTE) under age 50; evolving. At the time of this writing, current genetic non-
recurrent VTE; VTE at any age with a strong family history discrimination legislation in the United States includes The
of thrombotic disease (i.e. several affected relatives or Health Insurance Portability and Accountability Act
relatives with VTE under age 50); and VTE in an unusual (HIPAA), state laws, which provide added protection and
site (such as the hepatic, mesenteric, portal and cerebral the Genetic Information Non-discrimination Act (GINA).
veins) at any age [14, 15]. Testing should also be offered to
women with VTE who are pregnant or post-partum or
taking oral contraceptives [14, 16]. There is also general Genetic non-discrimination laws
agreement that women with pregnancy loss that is either
recurrent or late in pregnancy should be offered testing for HIPAA protects people with group health insurance from
thrombophilia [14, 16, 17]. It is less clear whether testing being denied insurance, having it cancelled, or having their
should be offered in cases of VTE in the setting of post- individual rates increased based on genetic test results.
menopausal hormonal therapy [14, 16, 18] or unprovoked HIPAA does have certain limitations, however; for exam-
VTE over age 50. Whether or not women with other ges- ple, it does not protect those who have individualized
tational vascular complications should be offered an health insurance plans. In addition, disability and life
evaluation is also controversial [14, 16]. insurance are not subject to these regulations. Because of
Testing is not recommended in certain scenarios, and the the gaps in HIPAA, many states have laws to provide
reader is encouraged to consult the previously referenced additional protection. Most states laws:
guidelines for a full review of the rationale for these con-
– prevent insurers from requiring genetic tests
traindications. Some scenarios in which testing is
– prevent insurers from using genetic test results to make
precluded are:
decisions about eligibility or rates
• General population screening: for all individuals, – apply to individual health plans as well as group health
before or during oral contraceptive or other hormone plans
therapy, during pregnancy, prenatally or in the newborn – prevent disclosure of genetic test results to third parties
period (for asymptomatic newborns), or in patients with without a patient’s knowledge
heart attack/stroke
Full, up-to-date Information on state laws is available at
• In healthy individuals with known risk factors for VTE
[Link].
(such as surgery, trauma, paralysis, or cancer), or
On April 25, 2007, the Genetic Information Non-dis-
• Venous thromboembolism (VTE) in patients over age
crimination Act (GINA) was passed in the US House of
50 who have known risk factors
Representatives. GINA will now go to vote in the senate
Genetic testing for hereditary thrombophilia is not gener- before approval by the president. GINA prohibits insurers
ally recommended for asymptomatic individuals prior to in both the group and individual health insurance industry,
adolescence. However, some exceptions exist—such as and employers, from ‘‘requesting or requiring’’ genetic
testing of siblings of children who have had arterial or testing of an individual or family or from using genetic
venous thrombosis in childhood. information to determine eligibility or establish premiums.
GINA also prohibits employers, including employment
agencies or labor organizations from using genetic infor-
Issues to be discussed with patients prior to testing mation to make hiring or promotional decisions or to
determine eligibility for training programs. More infor-
Both the CAP and the ACMG agree that written informed mation about the components and status of this law is
consent is not required prior to thrombophilia testing. available at [Link].
123
Genetic counseling—inherited thrombophilias 9
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