splenic artery thrombosis in a patient with prothrombin gene mutation jennifer teeter, d.o. mentor:...
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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
• 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.
• 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• WBC 15.5 Na 138 Ca 9.3
• HgB 15.7 Cl 100 T. Bili 1.0
• Hct 44.6 K 3.3 D. Bili 0.2
• Plt 188 CO2 29 T. Pro 7.4
• N 77% BUN 11 Alb 4.1
• L 7% Cr 0.9 ALT 29
• M 15% gluc 116 AST 29
• E 2% amylase 67 alk phos 66
• B 0 lipase 22
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 pelviswithout 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 pelviswith 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
• 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
• 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.
• 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:
– 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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