Advanced Emergency Nursing Journal

Vol. 34, No. 1, pp. 1015

C 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright 

Imaging
Column Editor: Denise Ramponi, DNP, CRNP, FAEN, CEN

A 21-Year-Old White Woman

Diagnosed With Cerebral Venous
Sinus Thrombosis Related to Oral
Contraceptive and Factor V Leiden
Holisa C. Wharton, MSN, RN

Abstract
Empirical research has established the fact that the use of oral contraceptives in young women
with the Factor V Leiden mutation increases the relative risk of cerebral venous sinus thrombosis.
Cerebral venous sinus thrombosis is a rare cerebral vascular injury whose ambiguous presentation
contributes to delayed and often-inaccurate diagnosis. This case report presents a 21-year-old White
woman with a severe headache who presented to the emergency department and was diagnosed
with cerebral venous sinus thrombosis. The purpose of this article is to educate advanced practice
emergency care nurses on the importance of understanding genetic and acquired risk factors in
diagnosing cerebral venous sinus thrombosis. A genetic risk assessment tool is introduced that
advanced practice nurses may incorporate into their routine assessments to evaluate the likelihood
of a genetic predisposition for illness, such as shown in this case study. Key words: cerebral venous
sinus thrombosis, Factor V Leiden, genetic red flags, oral contraceptive pill

HE USE of oral contraceptives (OCs)

by young women with Factor V Leiden (FVL) mutation increases the risk
of clotting disorders such as deep vein thrombosis (DVT), pulmonary embolism (PE), and
a rare cerebral vascular injury, known as
cerebral venous sinus thrombosis (CVST;
Cushman et al., 2004; Spannagl, Heinemann,

& Schramm, 2000; Welker, Lookinland, Tiedeman, & Beckstrand, 2004). Clot formation in
the brain more commonly develops in the
cerebral arteries that supply blood to the brain
tissue. Cerebral venous sinus thrombosis is a
clot in the veins that drain blood from the
brain tissue. Because of the low incidence
and highly variable clinical presentation, it is
important that advanced practice emergency
department (ED) nurses are aware of the risk
factors, clinical presentation, and diagnostic
methods used to identify this rare and lifethreatening cerebral vascular injury. Timely
diagnosis and treatment can significantly
contribute to positive health care outcomes in

Author Affiliation: School of Nursing, Clemson University, Clemson, South Carolina.

Disclosure: The author reports no conflicts of interest.
Corresponding Author: Holisa C. Wharton, MSN, RN,
School of Nursing, Clemson University, 528 Edwards
Hall, Clemson, SC 29634 (holisaw@clemson.edu).
DOI: 10.1097/TME.0b013e318243552c

10

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JanuaryMarch 2012

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patients with CVST. When indicated, prompt

initiation of anticoagulation reduces risk of fatal outcomes and severe disability. This case
report describes how health care providers
diagnosed a patient with a severe headache
with a CVST who presented in an ED. More
importantly, it emphasizes how knowledge of
genetic and acquired risk factors, along with
information gathered through patient history,
physical examination, and diagnostic evaluation, was used to properly diagnose and treat
this patient with atypical stroke.
RISK FACTORS
Risk factors for CVST are classified as either
acquired risk factors or genetic risk factors.
Acquired risk factors for venous thrombosis include smoking, surgery, trauma, pregnancy, and the use of estrogenic drugs such
as OCs (Lalouschek et al., 2005; Pezzini et al.,
2005; Zuber, Toulon, Marnet, & Mas, 1996).
The Dutch Venous Sinus Thrombosis Study
found that 85% of cases were using OC at
the time of their CVST (de Bruijn, Stam, &
Vanderbroucke, 1998; Kimber, 2002). Similarly, there is a long list of genetic risk factors, two of the more common being, Prothrombin 20210A and FVL (Gadelha, Andre,
Juca, & Nucci, 2004; Legnani et al., 2002). Prothrombin 20210A refers to a polymorphism
of the prothrombin gene. The prothrombin
gene produces the protein prothrombin in response to certain signals in the clotting cascade. The mutated version of this gene, Prothrombin 20210A, causes an overexpression
of its protein product leading to excessive clot
formation.
Factor V Leiden is the common name used
to reference a mutation of the F5 gene. F5
produces the protein, coagulation Factor V,
that promotes clot formation. In normal physiology, once the clot is formed and bleeding is
controlled, another protein, activated protein
C (APC), inactivates Factor V. The mutated F5
produces an altered form of Factor V protein
that is resistant to the inactivation by APC.
As a result of resistance to APC, thrombin
generation is prolonged. Individuals who

Cerebral Thrombosis Related to Oral Contraceptive

11

have one copy (heterozygous) of the mutated

F5 have an increased risk of abnormal clotting
three to eight times greater than the general
population (Kujovich, 2007). The risk of abnormal clotting in individuals who have two
copies (homozygous) of mutated F5 can be
as great as 80 times that of the general population (Kujovich, 2007). Although the FVL
mutation is less common in African Americans and Hispanics, approximately 5.1%
of Whites are heterozygous for the FVL
(Kujovich, 2007). Whereas FVL mutation is an
inherited cause of APC resistance, OCs are a
potential source of acquired APC resistance.
Therefore, young women who are unknowingly heterozygous or homozygous for FVL
and take OCs have an increased risk of developing a DVT, PE, and/or CVST. Young women
experiencing any of these conditions are most
likely to seek medical attention at a local emergency care facility. Deep vein thrombosis and
PE are relatively common and more easily recognized by advanced emergency care nurses.
Therefore, the focus of this case report is
the less common and ambiguous presentation
of CVST secondary to acquired and genetic
thrombophilia.

CASE STUDY REPORT

History of Current Illness
The medical records reported that a 21-yearold White, woman, accompanied by her parents, presented to the ED of a large universitybased medical center. The patient stated that
she developed a severe headache 4 days ago.
She described headache as a throbbing pain
in both the front of her head and the left side
of her neck. She stated that she was seen at
the ED of a small private hospital near her
college campus, and underwent a computed
tomographic (CT) scan of the head and a lumbar puncture, both of which were normal.
She was told that she had a migraine and was
prescribed oxycodone/acetaminophen (Percocet) and promethazine (Phenergan). The
patient returned home, but her pain did
not alleviate and was associated with several

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12

episodes of nausea and vomiting. She returned to the local ED the next morning and was discharged with instructions
to continue oxycodone/acetaminophen and
promethazine. Later that same day she went
to the ED at another larger area medical
center. She was evaluated and treated for
postlumbar puncture headache. Upon evaluation, she continued to complain of a headache
and weakness and numbness on the left side
of her body. Headache was worse with standing. She rated pain a 10/10 and denied any
fever or chills, vision or speech changes and
unsteady gait or history of head trauma.
Review of Systems
The review of systems was negative except
for the positive findings in the current history.
Medical/Surgical History
The medical and surgical histories were negative.
Medications
Ethinyl estradiol/levonorgestrel (Seasonale)
for the past 24 weeks.
Allergies
No known drug allergies.
Family History
She was an only child. Parents were alive. Her
mother had no significant medical history,
and her father had rheumatoid arthritis. No
bleeding or clotting problems were reported.

Advanced Emergency Nursing Journal

General appearance: Healthy, White female in physical distress.

Neck: supple.
Cardiovascular: regular rate and rhythm
without murmur or S3.
Respiratory: Lungs clear.
Gastrointestinal: Bowel sounds are normoactive.
Skin: No ecchymosis, warm, dry.
Neurologic: Slightly drowsy but arousable
oriented to person, place, time, and date. Language fluent. Speech without dysarthria.
Cranial nerves: Fund: no papilledema, no
spontaneous venous pulsations are noted.
Pupils were equal, round, and reactive to light
and accommodation. Extraocular movements
were intact. There was no facial droop. Palate
elevates symmetrically.
Motor examination: There was no pronator drift on the left. Deltoid is 5/5 on the left.
Hand grip was 4/5 on the left. Wrist extensors
4/5 on the left. Biceps 5/5 on the left. Triceps
5/5 on left. Deltoid 5/5 on left. Handgrip 4/5
on left. Left lower extremity was 5/5 throughout. Right side was 5/5 throughout with no
drift. Sensation was decreased to light touch
and pinprick to the shoulder of the left upper
extremity. Joint position sense was decreased
to the elbow in the left upper extremity.
Vibration was intact. Cerebellar: There was
a slight tremor in the left upper extremity;
otherwise intact. Gait: intact. Romberg Test
negative. Reflexes 1 + in the left brachioradialis, 1 + in the left triceps, 2 + in the left
biceps, 1 + in the right biceps, triceps and
brachioradialis, 2 + in bilateral patella, and
1 + bilateral Achilles.

Social History
The patient drank alcohol occasionally, denied smoking, was single, and lived with a
college roommate, active soccer player.
Physical Examination
Vital signs: Temperature, oral 36.6 C;
pulse rate 83 beats/min; respirations 18
breaths/min; blood pressure 128/90 mmHg;
and pulse oximetry 100% on 1 L per nasal
cannula.

Clinical Decision Making

According to Masuhr, Mehraein, and Einhaupl
(2004), the clinical presentation of CVST depends on the extension, localization and activity of the thrombotic process as well as on
the presence of venous collaterals (p. 12).
Headache is the most frequent symptom of
CVST and occurs in 75%95% of all cases
(Masuhr et al., 2004). The patient rated her

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JanuaryMarch 2012

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headache a 10/10 and described it as a rippling sensation. She equated the sensation to
concentric circles that extend away from a
pebble dropped in a pond. The patient also
experienced a generalized seizure. Focal or
generalized seizures are more frequently seen
in CVST than in arterial stroke and occur in
35%50% of all patients (Masuhr et al., 2004).
In the present case, the patient reported
weakness in her left upper extremity. The
association of focal deficits with headache,
seizures, or an altered consciousness is suggestive of CVST (Masuhr et al., 2004).
Other signs and symptoms, though not reported by the patient, include blurred vision,
vomiting, ataxia, cranial nerve palsies, and
the more life-threatening symptom isolated
intracranial hypertension. Intracranial hemorrhage occurs in 35%50% of patients with
CVST (Masuhr et al., 2004). Besides coma,
the presence of intracranial hemorrhage is
the most important prognostic factor for poor
outcomes (Masuhr et al., 2004). Masuhrs
study found that 53% of patients with stupor
or coma at the start of anticoagulation therapy
died whereas all patients with no more than
a mildly impaired vigilance survived (Masuhr
et al., 2004).
Diagnoses
Cranial CT is usually the first diagnostic technique performed in the ED for patients complaining of severe headache. However, in the
case of CVST, CT is normal in 25%30% of patients and its main value is to rule out other
conditions such as arterial stroke, tumors, or
brain abscess (Masuhr et al., 2004). Magnetic
resonance imaging and magnetic resonance
angiography are regarded the best tools for
diagnosis of CVST (Masuhr et al., 2004).
Shortly after returning to the ED, after
having a CT scan, the patient was noted to
have a generalized seizure that lasted approximately 1 min. The patient denied any prior
history of seizures. The CT scan findings were
suggestive of a cavernous venous thrombosis
and the plan was made for the patient to return to radiology for a CT venogram of the

Cerebral Thrombosis Related to Oral Contraceptive

13

head. A neurology consult was also ordered

and completed.
The CT venogram of the head confirmed
the presence of extensive dural venous sinus
thrombosis with complete occlusion of the
superior sagittal sinus, multiple cortical veins,
and the right transverse and sigmoid system.
The deep veins were patent and draining into
a small but patent left transverse and sigmoid
system. Complete blood chemistries and electrolyte panel were insignificant. The finding
from the chest radiograph was negative for
acute abnormalities.
Management
Upon the diagnosis of venous sinus thrombosis in this otherwise healthy, young, White
woman, a hypercoagulability workup was ordered (Table 1). The patient was admitted
to the neurology unit. Her medical therapy
included phenytoin (Dilantin) and levetiracetam (Keppra) to prevent seizure activity,
heparin for anticoagulation, and oxycodone/
acetaminophen for pain. A magnetic resonance imaging of the brain revealed confirmation of the extensive venous sinus thrombosis as well as the focal T2 hyperintensity
with restricted diffusion involving the right
posterior frontal precentral gyrus, which was
consistent with an early subacute infarction
and correlated with the symptoms of the patients left arm sensory deficit.
She was discharged from the hospital on
day 5, after being instructed not to drive
or operate heavy machinery for 6 months.
The patient and her parents were counseled
on the avoidance of OC and the symptoms
that could herald the onset of further sinus
thrombosis or an extension of her clot. The
following medications were prescribed: levetiracetam, oxycodone/acetaminophen, warfarin (Coumadin), and ibuprofen. A physician
closer to the university was contacted to monitor the patients international normalized ratio weekly. She was scheduled for followup in 2 months with both the neuroophthalmology and stroke clinics. She was also informed to return to the nearest ED if she had

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Advanced Emergency Nursing Journal

14

Table 1. Hypercoagulability testing and genetic testing

Test
Platelet count (thousand per uL)
Sed rate (mm/hr)
Pro time (s)
International normalized ratio
Partial thromboplastin time (s)
Homocysteine levels (umol/L)
Antiprothrombin M
Protein C assay
Protein S assay
Activated protein C resistance
FVL gene mutation prothrombin
gene mutation

Reference range

Results

150400
020
11.514.5 s
2.003.50
24.039.0 s
4.611.2
<25.0
60140
52135
>2.0

212
123
12.1 s
0.96
25.3
3.2
6.4
127
52
1.8
The presence of both normal and a
mutated R506Q Factor V allele
detected no evidence of G20210A
mutation detected

significant symptoms, including unilateral

limb weakness, severe headache, or loss of
vision.

for cerebral thrombosis. Therefore, these factors hinted at some underlying predisposition
for thrombosis. In this case, the underlying

DISCUSSION

Table 2. Genetic red flags

The initial screening for genetic risk factors

is a focused family health history. The presentation of the family history in the form
a pedigree facilitates the recognition of disease in multiple family members. The feasibility of a three-generation family history assessment in the emergency care setting is
low. But the incorporation of the genetic
red flags in the initial patient assessment
may be a more practical approach to identify patients at risk for genetic/environment
interactions. The genetic red flags, when considered collectively, indicate that there may
be a genetic etiology for the patients presentation. Like many checklists currently being used to facilitate the acquisition of patient data, the genetic red flags could be
added to existing assessment forms with minimal effort and training. As indicated by the
bullets in Table 2, the patient was relatively
young to incur a cerebral thrombosis. Most
medical professionals would not consider a
21-year-old, athletic, White woman at risk

If patient has any of the following indicators,

consider further genetic testing to rule out
underlying genetic disorder.
Family history of multiple affected family
members with the same or related
disorders, which may or may not follow an
identifiable pattern in the family.
Earlier age at the onset of disease than
expected.
Condition in the less-often-affected gender.
Disease in the absence of known risk
factors.
Ethnic predisposition to certain genetic
disorders.
Close biological relationship between
parents.
Note. Adapted with permission from Genetic Red Flags:
Quick Tips for Risk Assessment, by National Coalition
for Health Professionals Education in Genetics, Copyright
2011, retrieved August 2, 2011, at http://www.nchpeg.
org/index.php?option=com_content&view=article&id
=59:colorectal-cancer&catid=36:point-of-care&Itemid
=75

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JanuaryMarch 2012

r Vol. 34, No. 1

cause was the combined adverse effect of

FVL and OC that produced her thrombophilic
state. Finally, FVL mutation is found in 5.1%
of non-Hispanic Whites and should be considered when otherwise healthy young women
present with signs of DVT, PE, or CVST. Individually, these flags are suggestive of a genetic
cause of disease, but collectively they make a
much stronger argument to check for genetic
causal factors of CVST in the patient. Further
research is needed to examine the application of a health care genetic assessment tool
by advanced practice emergency nurses.

NURSING IMPLICATIONS
The absolute risk of CVST related to FVL mutation is too low to necessitate the screening of the general population for this genetic mutation (Vandenbroucke et al., 1994).
Although the relative risk of CVST is significantly increased in FVL-positive women using OC, the absolute incidence of venous
thrombotic events is low and fatal thrombotic
events are rare (Spannagl et al., 2000). The
fact that health care providers do not generally test women for the FVL before prescribing estrogenic drugs further warrants awareness of the acquired and genetic risk factors
by advanced practicing emergency nurses.
FVL mutation is present in up to 50% of
women with an estrogen-related thrombosis
(Kujovich, 2007). Such awareness may positively influence clinical decision-making and
ultimately improve health care outcomes for
patients experiencing CVST. This case report
urges advanced emergency nurse practitioners to consider CVST as a differential in young
women who report with stroke-like symptoms whose history reveal recent use of OCs,
hormone replacement therapy, or pregnancy.
More important, this case report illustrates the
importance of considering the combined effect of genetic and acquired risk factors to ensure the most appropriate medical decisionmaking.

Cerebral Thrombosis Related to Oral Contraceptive

15

REFERENCES
Cushman, M., Kuller, L. H., Prentice, R., Rodabough, R.
J., Psaty, B. M., Stafford, R. S., & Rosendaal, F. R.
(2004). Estrogen plus progestin and risk of venous
thrombosis. JAMA, 292(13), 15731581.
De Bruijn, S., Stam, J., Koopman, M., & Vanderbroucke,
J. (1998). Casecontrol study of risk of cerebral sinus
thrombosis in oral contraceptive users who are carriers of hereditary prothrombotic conditions. BMJ,
316, 589592.
Gadelha, T., Andre, C., Juca, A. A. V., & Nucci, M. (2004).
Prothrombin 20210A and OC use as risk factors
for cerebral venous thrombosis.Cerebrovascular
Disease, 19(1), 4952.
Kimber, J. (2002). Cerebral venous sinus thrombosis.Q J
Med, 95, 137142.
Kujovich, J. L. (2007). Factor V Leiden thrombophilia [Gene reviews]. Retrieved from www
.geneclinics.org/profiles/factor-v-leiden/details.html
Lalouschek, W., Schillinger, M., Hsieh, K., Endler, G.,
Tentschert, S., Lang, W., & Mannhalter, C. (2005).
Matched casecontrol study on FVL and the prothrombin G20210A mutation in patients with ischemic stroke/transient ischemic attack up to the
age of 60 years. Stroke, 36, 14051409.
Legnani, C., Palareti, G., Guazzaloca, G., Cosmi, B.,
Lunghi, B., Bernardi, F., & Coccheri, S. (2002).
Venous thromboembolism in young women. European Heart Journal, 23, 984990.
Masuhr, F., Mehraein, S., & Einhaupl, K. (2004). Cerebral
venous and sinus thrombosis. Journal of Neurology,
241, 1123.
Pezzini, A., Grassi, M., Del Zotto, E., Archetti, S., Spezi, R.,
Vergani, V., & Padovani, A. (2005). Cumulative effect
of predisposing genotypes and their interaction with
modifiable factors on the risk of ischemic stroke in
young adults. Stroke, 36, 533539.
Spannagl, M., Heinemann, A. J., & Schramm, W. (2000).
Are FVL carriers who use OC at extreme risk for
venous thromboembolism. The European Journal
of Contraception and Reproduction Health Care,
5, 105112.
Vandenbroucke, J. P., Koster, T., Briet, E., Reitsma, P. H.,
Bertina, R. M., & Rosendaal, F. R. (1994). Increased
risk of venous thrombosis in oral-contraceptive users
who are carriers of FVL mutation.Lancet, 344, 1453
1457.
Welker, G. C., Lookinland, S., Tiedeman, M. E., & Beckstrand, R. L. (2004). The role of genetics in the risk
of thromboembolism: Prothrombin 20210A and OC
therapy. Journal of the American Academy of Nurse
Practitioners, 16(3), 106138.
Zuber, M., Toulon, P., Marnet, L., & Mas, J. (1996). FVL
mutation in cerebral venous thrombosis. Stroke, 27,
17211723.

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