Case Discussion <Case Presentation> A 56-year-old female was admitted due to an episode of syncope one day prior to admission. The patient did not have hypertension, diabetes mellitus or other systemic diseases. Occasional chest discomfort and dyspnea on exertion have been noted for two days and she was treated at a local hospital. One day before admission, a spell of syncope occurred with a duration of less than 5 minutes and right cheek hematoma on account of falling to the ground at home. There was no aura, incontinence, convulsion, nausea/vomiting or limb weakness. Then she was sent to our emergency department for further evaluation. On arrival, the patient looked weak and irritable. Consciousness was clear. The body temperature was 35.5°C, the pulse rate was 103 beats per minute, and the respiration rate was 22 per minute. Blood pressure was 148/85 mmHg. Jugular venous pressure with estimated 8 cmH2 O, clear breathing sounds and regular heart beats without murmurs were found on physical examination. Liver was palpable 3 finger breath below right subcostal margin along right midclavicle line. There was no leg pitting edema. Sinus tachycardia with non-specific ST-T change was noted on EKG. CXR showed borderline cardiomegaly. Blood gas analysis under FiO2: 30% showed: PH: 7.38, PO2: 94.7, PCO2: 31.5, HCO3: 18, BE: -5.5 and O2 saturation: 97.2%. Because neurogenic syncope could not be ruled out, brain CT scan was arranged and it showed negative finding. Holter EKG study disclosed sinus rhythm from 56 to 140 beats per minute and no significant ST change. Pulmonary embolism was highly suspected. D-D dimer test was 349 μg/L (normal range: <250 μg/L). Echocardiography revealed dilated right ventrcile, adequate left ventricular performance and moderate tricuspid regurgitation. Thereafter lung perfusion study was performed and it was suggestive of high probability of pulmonary embolism. Computed tomography (CT) showed pulmonary embolism in both-side pulmonary arteries at the hilar region and bilateral lower lobes (figure 1 ). Table 1. Hematologic Laboratory Values: RBC Hb Hct MCV  PLT WBC D-D dimmer test M/L g/dL %  fL K/L K/L ug/L 3.77 11.8 34.9 92.4 257 6.6 349 Protein S Protein C Antithrombin III %(70-140) %(77-158) %(78-151) 43.3 69 108 Table 2. Biochemistry Values: BUN  Cr Na K Sugar GOT GPT mg/dL mg/dL mEq/L mEq/L mg/dL IU/L IU/L 28.8 1.12 144 4.00 120.7 59.0 92.5 Intravenous heparin was administered upon a high index of suspicion of pulmonary embolism and warfarin was also given simultaneously after the documentation of pulmonary embolism. rt-PA was infused after the finding of massive pulmonary embolism on chest CT. Finally the patient was discharged under stable condition after 2-week treatment. Figure 1. Image from CT pulmonary angiogram. Large clot (arrows) is present at the left and right pulmonary arteries. <個案分析> 本病人是pulmonary embolism的病例, 臨床上以昏厥來表現,但大部分pulmonary embolism的病人是以喘來表現, pulmonary embolism的病人有其危險因子,包括surgery, trauma, immobilization, obesity, old age, 服用contraceptives, pregnancy, cancer, cancer therapy, previous stroke or spinal cord injury, indwelling central venous catheter, obesity及immobilization是導致venous stasis及thromboembolism的重要機轉。另外重要的risk factors包括antithrombin-III deficiency, protein C or S deficiency, factors V Leiden mutation等，在無明確risk factors情形下，值得進一步評估。 病人呼吸沒有明顯囉音或哮喘音，給O2，PaO2不高,同時hyperventilation造成PaCO2下降。EKG多半是 sinus tachycardia,典型有S1Q3T3, 但不多見. 病人D-D dimer > 500 μg/L，可以高度懷疑pulmonary embolism。D-D dimer data若<500μg/L，可以用來rule out pulmonary embolism，有 > 90% negative predictive value。若 > 500μg/L，則建議進一步做venous thromboembolism的診斷評估。而D-D dimer data由於infection，tumor等疾病都會引起D-D dimer上升，D-D dimer < 500μg/L， pulmonary embolism的比率 < 10%，因此對診斷幫助較少，但也不能完全排除pulmonary embolism的可能性，這個病人就是這樣的狀況。Venous echo在acute pulmonary embolism診斷陽性率只有50%，如果是陽性則支持acute pulmonary embolism的診斷。如果陰性則不排除acute pulmonary embolism的診斷。 Pulmonary embolism的治療以抗凝血劑為主，包括heparin (LMWH or unfractionated heparin) and warfarin (coumadin)，合併使用，待warfarin效應出現後，可停用heparin, warfarin則維持PT(INR): 2-3. 至於thrombolytic agents則使用於 RV failure or unstable hemodynamics，至於massive pulmonary embolism則沒有規定一定非使用不可. 如何預防再發生acute pulmonary embolism: 1.改善acute pulmonary embolism 的 risk factors，增加活動量，減少體重, 2. 使用口服凝血劑warfarin，追蹤PT (INR) 維持在 2 – 3，持續半年或以上, 3. 如果病人 risk factors 是永久性的話，或反覆發生acute pulmonary embolism，則warfarin終生使用. 目前在NEJM 2003有關於預防recurrent venous thromboembolism的研究，發現warfarin使用半年後，在持續使用低劑量warfarin，INR 1.5 ~ 2.0，可以有效且安全減少venous thromboembolism的復發。穿彈性襪也是一個可行的方法。 繼續教育考題 1. (C) Which of the followings is not the possible source of pulmonary embolism？ A Thrombus in femoral vein B  Thrombus in iliac vein C Thrombus in left ventricle D Thrombus in subclavian vein E All of the above are possible sources 2. (D) Which one of followings is not correct ？ A Untreated pulmonary embolism has a high risk of recurrence B Anticoagulant therapy reduces the mortality in patients with pulmonary embolism by 75﹪. C Pulmonary embolism has a wide range of clinical presentation. D Unexplained syncope is the most common presentation of pulmonary embolism. E All of the above are correct. 3. (D) For the prevention of recurrence of pulmonary embolism，how long should anticoagulant treatment with warfarin or heparin be at least used？ A 2 weeks B 6 weeks C 8 weeks D 6 months E 12months 4. (E) Which of the followings is the potential invented thrombophilic defect in patients of pulmonary embolism？ A Antithrombin deficiency B Protein C deficiency C Protein S deficiency D Factor V Leiden mutation E All of the above are correct. 5. (A) Which one of the followings is not useful in the treatment of pulmonary embolism？ A Aspirin B Warfarin C  Heparin D  γ-tpA E  IVC tilter 6. (B) Which one of followings is not true for pulmonary embolism？ A Plasma D-D dimer level is elevated in patients with pulmonary embolism B Negative venous echo of lower extremities excludes the possibility of pulmonary embolism. C Troponin-I may be elevated in some patients with pulmonary embolism. D EKG is not a specific diagnostic tool for pulmonary embolism. E Absence of hypoxemia in arterial gas analysis does not exclude the possibility of pulmonary embolism. 7. (E) Which one of the followings is not useful in the diagnostic approach of pulmonary embolism？ A Echocardiography B Perfusion / ventilation lung scan C CT scan D Pulmonary angiography  E All of the above are useful 8. (E) The golden time of the use of thrombolytic treatment in acute pulmonary embolism is A ＜12hr B ＜3hr C ＜3days D ＜7days E ＜14days 9. (B) In patients with pulmonary embolism the echocardiography may have the findings that imply massive or submassive pulmonary embolism A Left atrial thrombus B Right ventricle dilatation C Left ventricle dilatation D Anterior wall myocardial infarction E All of the above 10. (D) What is the mortality rate in patients with untreated pulmonary embolism？ A ＜1﹪ B 3﹪ C 10﹪ D 30﹪ E ＞90﹪ 答案解說 (C )  左心室的血栓會引起週邊動脈阻塞，但不會進入靜脈系統，引起肺動脈栓塞。 (D) 肺動脈栓塞最常見的症狀是不明原因的喘、胸痛，暈厥也是肺動脈栓塞的臨床表現之一，但是比率較少，暈厥臨床上表示可能出現過嚴重的血行動力學異常或休克。 (D) 使用抗凝血栓可以減少肺動脈栓塞復發，至少使用6個月，因為使用6 個月的病人比使用3個月的病人復發率低，而有些病人已經復發過或伴隨有不可逆的病因（像惡性腫瘤等）則須終生預防。 (E ) 具有Inherited thrombophilic defect的病人較易發生Venous thromboembolism，包括venous thrombosis及pulmonary embolism。 (A ) Aspirin用來治療腦血管疾病、冠心病減少心血管疾病的發生及死亡，對於pulmonary embolism由於是來自於靜脈血栓抗血小板製劑沒有療效。 (B ) 肺動脈栓塞的來源可以是上、下肢或腹腔、骨盆腔靜脈血栓，下肢靜脈超音波未發現血栓仍無法排除肺動脈栓塞的可能性。 (E )  Echocardiography 可以診斷pulmonary embolism引起的Right ventricle dysfunction 及dilatation，CT scan 可以偵測肺動脈內血栓，而pulmonary angiography則是診斷肺動脈栓塞的基準檢查。 (E ) 血栓溶劑的使用在14天內仍可能有幫助，所以黃金時間設為14天，如果病人病況為血栓溶劑適應症，是可以早一點施打血栓溶劑。 (B) 肺動脈栓塞嚴重的病人，會引起急性肺心症，右心房、右心室擴大，原因是肺動脈阻力增加，肺動脈壓上升超出右心負荷，導致右心衰竭。 (D )  肺動脈若給予適當治療，死亡率可以大幅減少，目前證實可以減低死亡率的藥物是heparin，γ-tpA則較無確切証明可以降低死亡率。