**Needs of Special Populations**

Andra H. James, MD

Box 3967

Duke University Medical Center

Durham, NC 27710, USA.

Phone: Business - 919 681-5220; Home - 919 309-4475

Fax: 919 681-7861

E-mail: andra.

**Special Needs of Women**

**Contraception**

Older women are more likely to experience a DVT or PE than women during
their childbearing years, but women in their childbearing years who
experience a DVT or PE face certain unique problems. One problem is
contraception. The leading method of contraception in the United States
is the birth control pill. Women who take combined oral contraceptives
(with an estrogen and a progestin), are at a three- to four-fold
increased risk of thrombosis. For the average woman, the absolute risk
is still small, but for the woman with thrombophilia, or the woman with
a history of thrombosis, the risk becomes substantial. The new patches
may increase the risk further since the amount of estrogen absorbed is
60% higher than with the pill. The risk is offset by anticoagulation,
but women who are not taking anticoagulants have limited choices.
Prescribing anticoagulation for the purpose of allowing these women to
use combined hormonal contraception is not justified, as alternative
methods are available. One alternative is progestin-only contraceptives,
which have not been shown to increase the risk of DVT or PE.

**Management of Menopausal Symptoms**

Since postmenopausal hormone therapy with estrogen, or a combination of
estrogen and a progestin, increases the risk of breast cancer, stroke
and thromboembolic disease, hormone therapy should be prescribed only
when clearly indicated, primarily for symptom relief. In contrast to
progestin-only contraceptives which are not associated with an increased
risk of thrombosis, progestin in therapeutic doses for the management of
menstrual abnormalities is associated with a 5- to 6-fold increased risk
of thrombosis. Women with a history of thrombosis or thrombophilia, are
left with few, if any options for symptom relief.

**Heavy Menstrual Bleeding and Hemorrhagic Ovarian Cysts**

Women on anticoagulant therapy are vulnerable to heavy menstrual
bleeding (menorrhagia). While there are multiple reports of menorrhagia
in women on anticoagulant therapy, there is only one small study that
has reported on the prevalence. Menorrhagia, defined as a menstrual
blood loss of more than 80 ml per menstrual cycle, affects less than 5%
of women. In the small study of women on anticoagulant therapy, 5 of 11
complained of menorrhagia, and overall, the mean menstrual blood loss
was 98 ml. Evaluation and management of menorrhagia in women on
anticoagulant therapy is similar to that for other women and requires
consideration of a woman's age and reproductive plans, but surgery may
pose particular hazards in terms of both thrombosis and hemorrhage.

An infrequently considered complication of anticoagulant therapy is
hemorrhagic ovarian cysts. Ovulation is not normally accompanied by any
significant amount of bleeding, but in a woman on anticoagulant therapy,
the potential exists for bleeding into the peritoneal cavity, or
bleeding into the residual follicle resulting in a hemorrhagic ovarian
cyst or retroperitoneal hematoma. While there are multiple case reports
documenting ovarian hemorrhage in women on anticoagulant therapy, there
is little data about the prevalence of the problem, but in one series of
46 women who required surgery for hemorrhagic ovarian cysts, half were
on anticoagulant therapy. Birth control pills, which prevent ovulation,
reduce menstrual blood loss and eliminate the risk of ovarian
hemorrhage, are often withheld due to fear of thrombosis.

**Special Needs of Pregnant Women**

Women have a 4-fold increased risk of DVT and PE during pregnancy and a
20-fold increased risk after delivery. Their hypercoagulable state has
likely evolved as protection against the bleeding challenges posed by
both miscarriage and childbirth. Women with a history of thrombosis who
are not on lifelong anticoagulation will often require anticoagulation
during pregnancy and the first 6 weeks postpartum. Women who are on
lifelong anticoagulation will require conversion from warfarin. Since
warfarin crosses the placenta and is associated with an increased risk
of miscarriage, birth defects, fetal hemorrhage and neuro-developmental
abnormalities in childhood, most women who require anticoagulation
during pregnancy are prescribed some form of heparin, which usually
requires two injections per day. Low-molecular-weight heparin, which is
easier to use and has fewer side effects than traditional,
unfractionated heparin, has a longer half-life, which is an advantage
during pregnancy, but a disadvantage at the time of delivery. Besides
the bleeding risk, anesthesiologists are reluctant to administer
regional anesthesia if low-molecular-weight has been given in the
previous 12 to 24 hours. Planning for delivery requires coordination
among the specialists involved.

While thrombophilia may confer a survival advantage in the face of a
bleeding challenge, thrombophilia does not improve the outcome of
pregnancy. The optimal outcome of pregnancy is achieved by normal
coagulation at the interface of the placenta and the uterus.
Consequently, women with thrombophilia are more likely to experience
poor pregnancy outcome, examples of which are given in Table 1. Women
who are not on anticoagulants prior to pregnancy, but have a history of
thrombosis or have thrombophilia and a history of poor pregnancy
outcome, are also candidates for anticoagulation during pregnancy. Both
mothers and their unborn babies require close monitoring.

While some experts would recommend thromboprophylaxis throughout
pregnancy and for 6 weeks postpartum for all women with thrombophilia,
anticoagulation is not routinely recommended for those who have no
personal history of thrombosis or poor pregnancy outcome. In these
women, the benefits of anticoagulation probably do not outweigh the
risks. Alternative strategies to reduce the risk of venous
thromboembolism in this group should be considered.

**Thromboses in Unborn Babies**

Thromboses in unborn babies are relatively rare events but have
devastating consequences. Early in gestation, during the critical period
for fetal development, thromboses can obstruct blood flow to developing
organs or extremities and result in birth defects. Later in gestation,
thromboses that have been reported in the fetal renal veins, vena cavae,
cerebral venous sinuses, umbilical veins and placental vessels sometimes
with lethal results. There are no data on how to treat these fetal
events during pregnancy and only speculation on how to prevent
recurrences in future pregnancies.

**Thromboses in Infants **

In infants, the single most important risk factor for the development of
thrombosis is the presence of an indwelling catheter. 80% of venous
thromboembolism in newborns is due to intravenous lines either in the
upper body or the umbilical veins. 13% of umbilical vein catheters
develop thromboses resulting in long term consequences for survivors.
Spontaneous events, unrelated to catheters are rare and occur in sites
similar to those that occur in utero such as those involving the renal
veins, which can cause kidney damage, and those involving the cerebral
venous sinuses, which can cause stroke. Treatment of thromboembolism in
newborns consists of either anticoagulation or thrombolysis.

A rare but potentially lethal condition, purpura fulminans, may occur in
infants homozygous for inherited thrombophilia (with two copies of the
defective gene). The classical presentation consists of cerebral or eye
damage before birth, skin lesions, and thromboses. Survivors require
replacement therapy with fresh frozen plasma.

**Thromboses in Children**

Like in infancy, most deep vein thromboses and pulmonary emboli are
related to catheters used in the treatment of acute or chronic illness.
Like in adults, other events are associated with trauma, surgery,
autoimmune disease, sickle cell disease, malignancy or thrombophilia.
There are important differences, however, in the epidemiology, diagnosis
and treatment of DVT and PE in children compared to adults. These issues
are summarized in Table 2. Current approaches are extrapolated from
adult patients. The development of thrombosis in children and the
responses to treatment, however, are distinct from those in adults and
deserve special attention.

**Assembling a Team to Meet the Needs of Individuals **

** **Unlike in cases of arterial thrombosis where patients who have had
a heart attack have a cardiologist and those who have had a stroke have
a neurologist, individuals who experience DVT or PE often find that
there is no specialist who directs their care. They may be followed by
an internist, family practitioner, nurse practitioner or physician
assistant who may or may not have any special interest or expertise in
DVT or PE. Community hematologists, who devote approximately 90% of
their time to the care of cancer patients, may have little experience
with thrombosis patients. The ideal team, on the other hand, includes a
hematologist who has expertise in coagulation and is able to provide
consultation, a pharmacist who is knowledgeable about anticoagulation, a
nurse who is able to educate the patient and a primary provider.

**Assembling a Team to Meet the Needs of Families**

** **Families have needs above and beyond the needs of individual
patients. Young adults and children with a spontaneous DVT or PE often
have an inherited risk factor for thrombosis (inherited thrombophilia).
Inherited thrombophilia has implications for family members,
particularly whom should be tested and whom should be treated. The ideal
team to meet the needs of families includes a genetic counselor who is
knowledgeable about the implications of familial thrombosis and is able
to provide guidance concerning testing.

**Creating a Center that Meets the Needs of the Community**

** **The ideal center provides consultative services for both inpatients
and outpatients and provides direct care in complex cases. The ideal
center also includes a coagulation laboratory that provides a full-range
of coagulation testing on site. The idea center provides education for
consumers and providers through websites, presentations, printed
materials and protocols.

**Meeting the Needs of the Nation**

** **Recently, Spyropoulos and Haire described the Clinical Thrombosis
Center as an entity developing from an already established
anticoagulation management service under the direction of a physician
with expertise in the management of DVT, PE and anticoagulation. Of
note, this model does not include expertise in the management of
bleeding disorders, even though major hemorrhagic complications occur in
1-2% of patients on warfarin each year, nor does the model address the
needs of special populations.

** ** In 2001, the Division of Hereditary Blood Disorders of the Centers
for Disease Control and Prevention initiated a program to conduct
research in the reduction and prevention of complications of thrombosis,
thrombophilia, and bleeding disorders. The intended purpose of the
program was to:

-   Determine the value of a multi-disciplinary team in providing care
    to persons with coagulation disorders.

-   Assess unmet needs and identify outreach strategies to improve
    access to care.

-   Develop effective messages aimed at disease management and
    prevention.

-   Foster the development of training programs to enhance provider
    skills.

A total of 8 centers now receive federal support in the initial pilot
program. They serve as models for the delivery of care and form a
network to investigate how care is delivered.

**Table 1. Examples of Poor Pregnancy Outcome**

-   Spontaneous abortion (miscarriage)

-   Fetal growth restriction (inadequate growth of an unborn baby)

-   Intrauterine fetal demise (stillbirth)

-   Placental abruption (premature separation of the placenta)

-   Preeclampsia (high blood pressure of pregnancy)

**Table 2. Issues in the Diagnosis and Treatment of DVT in Children**^,^

-   The coagulation system changes with age.

-   Children have high circulatory demands and may be more crippled with
    the post-thrombotic syndrome than adults.

-   Children suffer different illnesses and take different medications
    than adults.

-   Children may not be able to cooperate with diagnostic procedures and
    anesthesia may be required.

-   Maintaining intravenous access may be difficult.

-   There are no pediatric formulations of any anticoagulants.

-   There is no liquid warfarin or pediatric doses of injectables in
    pre-filled syringes.

-   Different diets and formulas contain vastly different vitamin K
    levels.

-   Infants and small children my not understand the need for therapy
    and adolescents may not want to cooperate.

-   Children are dependent on their parents who may not do what is in
    their child's best interest.

**References**