Splenic Artery Thrombosis in a
Patient with Prothrombin Gene
Mutation
Jennifer Teeter, D.O.
Mentor: Dr. Kamal D. Tourbaf, M.D.
Virchow’s triad
• The major theory delineating the
pathogenesis of thrombosis
– Alterations in blood flow
– Vascular endothelial injury
– Inherited or acquired hypercoagulable state1
Inherited Thrombophilia
• Factor V Leiden mutation
• Prothrombin gene mutation2
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•
•
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Protein C deficiency
Protein S deficiency
Antithrombin deficiency
MTHFR mutation
Acquired risk factors
• 50% of thrombotic events in patients with
inherited thrombophilia are associated with
an acquired risk factor
– Pregnancy
– Surgery
– Prolonged bedrest
– Malignancy
– Trauma
– Smoking
– Oral contraceptives3
• The majority of thrombosis are venous
rather than arterial.
• The majority occur within the lower
extremities.
Our Case
• We describe a patient with prothrombin
gene mutation and tobacco use causing
splenic artery thrombosis and subsequent
splenic infarct after abdominal trauma.
History
• 43-year-old Caucasian male presented to
the ER with complaints of nausea and
vomiting for 3 days.
• In addition, he had left upper abdominal
and left flank pain for 1 day.
ROS
• Left lower chest and left upper abdomen
bruised 3 weeks prior to presentation after
he bumped into a shelf.
• Denies fever, urinary burning or frequency,
SOB or changes in bowel habits.
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PMHx: Gout
PSHx: none
Meds: none
Allergies: NKDA
Social: +tobacco <1ppd X 15 years,
denies alcohol or drug use.
• FHx: mother had breast cancer and LE
DVT’s
Physical Exam
• Vitals: 133/89 100 20 100.5 100%RA
• 43-year-old caucasian male in moderate
distress, A+Ox3
• HEENT: NCAT, EOMI, PERRLA, OMM,
clear pharynx
• Neck: no bruits, no thyromegaly
• Heart: RRR S1S2, no murmurs
• Lungs: CTA b/l no w/r/r
PE con’t
• Abdomen: soft, nondistended, +BS,
significant LUQ and left flank tenderness
with minimal palpation and with deep
inspiration. No rebound or guarding.
• Ext: no edema, negative homans
• Neuro: CN II-XII grossly intact, muscle
strength, reflexes, sensation intact
• Rectal: heme occult negative
Labs
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WBC 15.5
HgB 15.7
Hct 44.6
Plt 188
N 77%
L 7%
M 15%
E 2%
B0
Na 138
Cl 100
K 3.3
CO2 29
BUN 11
Cr 0.9
gluc 116
amylase 67
lipase 22
Ca 9.3
T. Bili 1.0
D. Bili 0.2
T. Pro 7.4
Alb 4.1
ALT 29
AST 29
alk phos 66
U/A
• Negative glucose, ketones, leuk. Esterase,
nitrites, protein, bilirubin
• + trace blood, few bacteria, 5-10
squamous epithelial cells
EKG
• Sinus tachycardia
CT abdomen and pelvis
without contrast
• Subtle stranding involving the superior
aspect of the body of the pancreas and
around the left adrenal gland
• Left renal cyst
• No evidence of hydronephrosis, renal,
ureteral or bladder calculi
CT abdomen and pelvis
with contrast
• Enlarged spleen, 15.1 cm, with patchy
areas of enhancement. The majority of the
spleen does not appear to enhance,
suggestive of ongoing splenic infarction.
• The splenic artery also does not enhance,
suggestive of thrombosis
• Left renal cyst
Hospital Course
• The patient was followed by a vascular
surgeon, a general surgeon and a
hematologist.
• He was managed conservatively with IV
heparin which was bridged to coumadin.
• His pain was controlled with analgesic
medication.
• A cause for the thrombosis was evaluated.
Studies
• Lower extremity venous dopplers:
negative for DVT
• Normal lower extremity arterial dopplers
• 2D echo: left ventricular EF 50%; poor
overall images, normal right ventricular
systolic function, mild thickening of aortic
valve leaflets.
• TEE with bubble study: normal left and
right ventricular systolic function. No
evidence of cardiac source of embolism.
Hypercoagulable Workup
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•
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Protein C 114% (71-146%)
Protein S 105% (74-146%)
No resistance to activated protein C
Factor V Leiden negative
Antithrombin III 94% (81.1-125.9%)
Con’t
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C-ANCA <6 u/ml (negative)
P-ANCA <6 u/ml (negative)
Phospholipids 207 mg/dL (151-264 mg/dL)
Thrombin time 20 sec (16-23 sec)
No evidence of lupus anticoagulant
Cardiolipin antibodies normal
Positive Labs
• Factor II mutation positive
– Genotype: heterozygous
• + one copy of MTHFR mutation
– The presence of one copy has not been
associated with an increased risk for
hyperhomocysteinemia or vascular disease.
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•
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CRP 11.300 mg/dL
ESR 74 mm/hr (0-15 mm/hr)
Fibrinogen 660 mg/dL (250-500 mg/dL)
Homocystine 18.3 umol/L (5-15 umol/L)
Factor VIII 209% (50-150%)
Acute gouty attack
• Right second metatarselphalangeal joint
during his course of illness.
• Uric acid 6.0  9.3
• Treated with colchicine
Repeat Labs
• Fibrinogen 302 mg/dL (250-500 mg/dL)
• Homocystine 14.4 umol/L (5-15 umol/L)
• Factor VIII 147% (50-150%)
• Therefore, it is felt that the initial elevation
of this patient’s fibrinogen, homocystine
and Factor VIII were due to an acute phase
response secondary to the splenic
infarction and gouty attack.
• We concluded that this patient’s
hypercoagulability is most likely a result of
his Factor II mutation.
• In addition, the patient’s abdominal trauma
and tobacco use may have played an
additive role.
• We recommended long-term
anticoagulation and discontinuation of
tobacco use.
• Family members, including siblings and
children, were advised to be tested for the
Factor II mutation.
DISCUSSION
Splenic Infarction
• Acute occlusion of the splenic artery
results in infarction of the splenic
parenchyma.
• Patients present with left upper quadrant
pain, fever, chills, nausea, vomiting,
pleuritic chest pain and left shoulder pain5.
Splenic Infarction
• Usually encountered in association with
– hematological diseases
– Thromboembolic states
– Vasculitides: SLE with lupus anticoagulant or
antiphospholipid antibodies5
– Sickle cell disease
– Wegener’s granulomatosis
– Cocaine abuse6
Splenic Artery
• Abnormalitites of the splenic artery,
particularly stenosis and occlusion, are rare
types of acquired disorders of splanchnic
circulation.
• Etiological factors:
– Blunt trauma
– liver transplantation surgery or pancreatectomy
– torsion of the wandering spleen5,7-8
Splenic Artery Thrombosis
• Thrombosis of the abdominal aorta and
splenic artery in antiphospholipid
syndrome9
• Thromboembolic process of cardiac origin
causing stenosis of the splenic artery10
• Secondary to oral contraceptive use11
• Thromboembolic splenic infarction due to
atherosclerosis of the thoracic aorta and
splenic artery12
Splenic A. Thrombosis Con’t
• Spontaneous splenic infarction after
sumatriptan use13
• DM with atheromatous arteries and
thrombosis of the sclerosed splenic
artery14
• Asymptomatic splenic artery occlusion in a
child discovered with doppler U/S15
• To our knowledge, a case on splenic
artery thrombosis in a patient with
prothrombin mutation has never been
reported.
Thrombophilia
• The blood has an increased tendancy to clot
• Risk Factors:
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Inherited risk factor
Obesity
Cancer
Inflammatory bowel disease
Antiphospholipid antibodies
Recent surgery
Trauma
Prolonged immobility
Pregnancy
Oral contraceptive use
Hormone replacement therapy16
Thrombophilia Con’t
• Thrombophilia is a prominent risk factor for
venous thromboembolism.
• The role of thrombophilia in determining
the risk of arterial thrombotic events is less
well defined.
Prothrombin
• A protein in the blood that is required to
form fibrin which combines with platelets
to form blood clots.
• A mutation in the prothrombin gene, also
called prothrombin variant, prothrombin
G20210A, or factor II mutation, has been
associated with a 30% higher plasma
prothrombin level and therefore an
increased tendency for thrombosis18.
Prothrombin Con’t
• Heterozygous or homozygous
• Heterozygous mutations are found in about 2%
of the US Caucasian population.
• The homozygous form is uncommon, 1/10,000.
• Heterozygous prothrombin mutation increases
the risk of developing a DVT by 2-3 times16.
• It plays a role in cerebrovascular ischemic
events in those less than 60 years of age. There
is conflicting results when evaluating the role of
prothrombin gene mutation in acute myocardial
infarction19-21.
• Many people with this mutation will never
develop a blood clot
• Often, people will have additional risk
factors for clot formation.
• If a patient has the prothrombin mutation
but has not developed a blood clot, they
should be counseled about reducing or
eliminating other factors that add to their
risk of developing a blood clot in the
future16.
• Several studies have shown a correlation
between tobacco use and an increased risk for
venous thromboembolism22-24.
• A large population-based study investigated the
VTE risk following a minor injury and concluded
that a minor injury occurring in the preceding 3
to 4 weeks was associated with a 3- to 5-fold
increase in DVT risk26.
• Risk factor modification is also important for
preventing arterial disease.
• It is likely that, in our patient, his tobacco use
and/or abdominal blunt trauma contributed to his
development of thrombosis.
Acute gouty attack
• We were unable to find any evidence that gout is an
independent risk factor for increased coagulabilty.
• Nevertheless, gout is associated with a number of
risk factors for cardiovascular disease including
hypertension, obesity, a high alcohol intake and
hyperlipidemia.
• In view of the already raised thrombotic risk profile in
gout patients as a group, one study showed that the
hyperfibrinogenemia was only present during the
acute attack of gout, presumably as an acute phase
response.
• They concluded that it is unlikely that the
hyperfibrinogenemia noted during acute attacks of
gout contributed significantly to the chronically
raised cardiovascular risk profile of long-term gout
patients27.
Acute Phase Response
• Raised fibrinogen, homocystine and factor VIII
levels have been recognized as risk factors for
thrombosis.
• Although these levels were initially elevated in
our patient, they did return to normal limits after
the splenic infarction and the resolution of his
acute gouty attack.
• We concluded that these elevations were due to
the acute phase response and most likely did
not play a significant role in the risk of
thrombosis in this patient
CONCLUSION
• Thrombosis occurs as a result of disruption of blood flow,
vascular endothelial damage and/or a hypercoagulable
state.
• A common cause of inherited thrombophilia is
prothrombin gene mutation.
• Thrombophilia is a prominent risk factor for venous
thromboembolism; however, the risk for arterial events is
less well defined.
• There are many reported causes for splenic artery
thrombosis and splenic infarction.
• However, we believe we are the first to report a case of
splenic artery thrombosis and subsequent splenic
infarction in a patient with prothrombin gene mutation
and tobacco use who sustained abdominal trauma.
• Although our patient had elevated fibrinogen,
homocystine and factor VIII levels, we determined that
these were acute phase reactants.
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