Case Discussion < Brief History >      A 55-year-old man suffered from intermittent abdominal pain for one week. He is a HBV carrier and had been well until 7 months ago when he suffered from left upper quadrant pain and one episode of hematemesis (about 400 ml fresh blood and blood clot). Panendoscopy was performed at that time and showed gastric ulcer without evidence malignancy. He was discharged after component therapy and proton pump inhibitor use. However, intermittent abdominal pain over epigastric area and left upper quadrant with fullness sensation developed one week prior to this admission. The pain occurred half an hour after meals, persisted for about half an hour and was relieved by stool passage. Black-colored stool was also noted recently. He took some medication by himself without benefit in the following days. The abdominal pain aggravated with radiation to back on July 15, 2002 and he was brought to the ER for further evaluation and management.      On arrival, the temperature was 36℃, the pulse was 70 beats per minute, and the respiratory rate was 16 per minute. The blood pressure was 120/70 mmHg. He appeared acute ill-looking with knee-chest position because of abdominal pain. The consciousness was clear. The conjuntivae was pale and the sclerae was anicteric. There was neither injected throat nor oral ulcer. The neck was supple without lymphadenopathy or engorged jugular vein. The breath sounds were clear. The heart sounds were regular without murmurs. Inspection of the abdomen revealed superficial vein engorgement. The auscultation revealed normoactive bowel sounds. The abdomen was soft and flat. The liver was impalpable but the spleen was enlarged with 4 finger breadth below left costal margin. Epigastric and left upper quadrant tenderness on deep palpation without rebound tenderness was also noted. The rectal examination was normal except internal hemorrhoids. There was no pitting edema over extremities. < Laboratory Examination > 1. Hemogram   WBC RBC Hb Hct MCV PLT  Band Seg Eos Baso Mon Lym K/μL M/μL  g/dL % FL K/μL %  % % % % % July 15, 2002 18.55 5.12 11.5 35.1 68.6 1091  0 84 2 2 4 7 July 29, 2002 17.97 4.69 10.7 32.8 69.9 765 0 68 5 0 7 20 Aug. 1, 2002 13.37 4.85 11.1 34.6 71.3 941 0 72 4 3 5 16 Aug. 3, 2002 8.73 4.28 9.7 30.6 71.5 604 0 73 4 8 5 17 2. Blood chemistry   Albumin Globulin T-Bil D-Bil AST ALT ALP GGT LDH Glu AC g/dL g/dL mg/dL mg/dL U/L U/L U/L U/L U/L mg/dL July15, 2002     0.65 0.3 32 26       92 July 20, 2002     0.8 0.3 28 10 145 20 504   July 23, 2002 3.5 3.9 1.0 0.4 34 14 160 24 613   Aug.1 , 2002 3.8 4.0 0.6  0.3 41 20 165 29 650          BUN Cre UA Na K Ca TG T-CHO Amylase Lipase Mg/dL mg/dL mg/dL mmol/L mmol/L mmol/L mg/dL  mg/dL U / L U / L July15, 002 27.8 1.59   137.5 4.59       115 260 July18,2002                 69 125 July23,2002 19 0.8 3.4 135 4.9 2.25 81 118     Aug.1,2002 20  1.0                   3. Stool exam ( O.B.): July 17,2002: +/- ;          July 24, 2002: 4+ 4. Coagulation and DIC profile (4 unit of fresh frozen plasma have been transfused on July 19)   PT (sec)  PTCont. (sec) PT INR PTT(sec) PTTCont. 3P FDP D-Dimer  Fibrinogen  July 18, 2002 19.1 12.7 1.6 58.4 38.1 2+ 10-20 1.69   July 23, 2002 16.5 10.8 1.4 54.8 35.1 Negative 5-10 2.92 364 July 29, 2002 15.4 11.1 1.3 57.1 35.7 (Negative) (<10) (<0.5) (214 -474) Protein S Ag : Total : 80 (80-180 )   Protein S Ag :Free : 45 ( 70-180 ) Protein S:Fun : 69 (68-155 ) Protein C: Fun: 78 ( 70-192 ) Antithrombin III: Ag: 97 ( ≧85 ) Antithrombin III: Fun: 79 ( ≧85 )     < Course and Treatment >        Leukocytosis, thrombocytosis, and slightly elevated lipase level was noted. Acute pancreatitis was suspected initially, so NPO, fluid resuscitation and pain control were given. His pain relieved and follow-up lipase level decreased. Abdominal echo revealed: 1. obliterated portal vein , 2. marked splenomegaly , 3. dilated left intrahepatic duct, and 4. cavernous transformation at hepatic hilum. (Fig.1) Mesenteric ischemia has been suspected but abdominal CT showed no evidence of thrombosis of main trunk of superior mesenteric artery. Color Doppler ultrasound revealed obliteration of portal vein with cavernous transformation. (Fig.2) MR angiography revealed enhanced fibrotic band like lesion surrounding extrahepatic portal vein. Minimal vessels could be traced including splenic vein and superior mesenteric vein. (Fig.3) Thrombosis of splenic vein and superior mesenteric vein was impressed. Panendoscopy showed varices over esophagus, stomach and duodenum related to portal hypertension. (Fig 4 ) Beta-blockers with propranolol were given for prophylaxis of variceal bleeding. Tumor markers including alpha-fetoprotein, CEA, CA19-9 and PSA have been checked and were all within normal limit. Due to the persistent thrombocytosis without infection signs, bone marrow studies with aspiration and biopsy was performed on July 26. The pathology was compatible with chronic myeloproliferative disorder. Homocysteine level ,protein C, protein S, anti-thrombin III, anti-cardiolipin antibody and anti-phospholipid antibody were checked and all were within normal limit. Essential thrombocythemia was favored based on the clinical and pathological findings. Therefore, hydroxyurea was prescribed for control of platelet count. His abdominal pain improved gradually and he was discharged on August 3, 2002 and was followed up at hematologic outpatient clinic. Warfarin was added for the possible risk of recurrent thrombosis since August 30. < Case Analysis >      This is a case of essential thromocythemia ( ET ) , who presented with symptoms and signs of portal vein thrombosis, including splenomegaly and variecs bleeding. Essential thrombocythemia may be asymptomatic ( 57 % ) and may present with bleeding, arterial or venous thrombosis, or some vasomotor symptoms ( headache, dizziness , erythromelalgia). The treatment of ET is based on risk stratification, and the high risk group refer to those are older than 60 years of age or with a history of thrombosis or extreme thrombocytosis. Treatment is necessary only in those with high risk and several drugs have been showed to be effective. Hydroxyurea reduced the thrombotic event from 45 % to 9 % but carries the risk of leukemia. Anagrelide inhibit megakaryocyte maturation in bone marrow and control thrombosis in more than 90 % of patients. Aspirin is indicated in those with vasomotor symptoms, transient ischemic accident or unstable angina. In pregnant female patients, interferon α can be considered. In patients with acute portal portal vein thrombosis, intravenous heparization followed by oral anticoagulation recannalize more than 80 % patients. In patients with chronic portal vein thrombosis, treatment aims at control of portal hypertension with endoscopic follow-up and propranol use. Chronic anticoagulation also has been used to be helpful in reducing the risk of splanchnic venous infarction. 繼續教育考題 1. (D) Which of the following image modality has the best sensitivity of detection of portal vein thrombosis ? A KUB B Abdominal CT C B-mode ultrasound D Color Doppler ultrasound E UGI series 2. (E) Which of the following image modality has the best evaluation of the extent of portal vein thrombosis ? A KUB B Abdominal CT C B-mode ultrasound D Color Doppler ultrasound E MR angiography 3. (E) Which of the following disorders may cause thrombocytosis ? A Systemic inflammation B Acute bleeding C Post-splenectomy D Myeloproliferative disorders E All of the above 4. (E) Which of the following disorders are not included in myeloproliferative disorders? A Polycythemia vera B Essential thrombocythemia C Myelofibrosis with myeloid metaplasia D CML E AML 5. (B) Which of the following disorders is characterized by thrombosis and bleeding ? A Polycythemia vera B Essential thrombocythemia C Myelofibrosis with myeloid metaplasia D CML E AML 6. (E) Which of the following clinical finding is included in the diagnostic criteria of essential thrombocythemia? A Platelet count ≧ 600 K/μL B Hematocrit < 40 C No Ph1 chromosome D Absent or < 1/3 collagen fibrosis of BM E All of the above 7. (E) Which of the following medication can be used to treat essential thrombocythemia? A Hydroxyurea B Analgrelide C Aspirin D Interferon α E All of the above 8. (E) Which of the following statements is not true ? A The life expectancy of patients with ET is almost normal B About 50 % of ET patients experience more than one thrombotic episode within 9 years after diagnosis C Analgrelide has been shown to be non-leukemogenic D Propranolol and endoscopic treatment is the first line in prevention of bleeding from portal vein thrombosis E Antcoagulation treatment is not recommended in managing chronic portal vein thrombosis because of high risk of causing bleeding 9. (E) Which of the following condition may lead to formation of portal vein thrombosis ? A Malignancy B Antiphospholipid syndrome C Protein C deficiency D Pancreatitis E All of the above 10. (C) Which of the following statements about ET is not true ? A 75 % patients develop splenomegaly B < 15 % patients develop hepatomegaly C The LAP score is mostly decreased D < 5% patients develop leukemia E ET is diagnosed by exclusion

答案解說 (D) Color Doppler Ultrasound ( 93 %)> B-mode ultrasound (64%) >CT (50) (E)MR angiography has the following advantages including: multi-plane image and minimal invasiveness, distinction of slow flow and thrombosis, not affected by gas (E) Reactive thrombocytosis includes systemic inflammation, malignancy, acute bleeding, iron deficiency and post-splenectomy (E) (B) About 50 % of ET patients have thrombotic events and 12 % patients have bleeding episodes (E) (E) (E) Anticoagulation treatment don't increase the risk or severity of bleeding (E) (C) The LAP score in ET patients is normal or increased