Case Presentation A 67-year-old man presented to the emergency department with five-day history of non-productive cough and progressive dyspnea and a one-day history of right-sided pleuritic pain. According to the patient and his family statement, he had been well until about one month earlier, when pain developed in his right leg. Two day later, the pain resolved and he didn't ask for any medical help except some Chinese herb taken. However, non-productive cough and progressive dyspnea were noted five days prior to this admission. He visited to a local hospital for help and was diagnosed as left-lower-lobe pneumonia and oral antibiotics had been initiated for four days, while the condition didn't improve. At the same time, right-sided pleuritic pain was noted for one day. The patient, who resided in Taipei, had stopped smoking 18 years earlier an drank a moderate amount of alcohol since his teenage. There was a history of type 2 diabetes mellitus, for which he took an unknown oral medication. There was a history of diabetes mellitus in several relatives, and a sister had had three-later-term spontaneous abortions, without further evaluation. The patient denied chest pain, fever, chills, night sweats, weight loss, or any travel history in recent half a year. There was no family history of stroke or clotting disorders. On examination, the patient had marked respiratory difficulty, with a respiratory rate of 28 breaths per minute. The temperature was 36.4℃, the pulse was 137. The blood pressure was 95/60 mmHg. His consciousness was clear. No rash, patechiae, septic lesions, or lymphadenopathy was detected. The lungs were clear. A grade 2/6 systolic murmur was present at left lower sternal border ; a third heard sound was not heard. The liver was hard and descended 4 to 5 cm below the right costal margin; the spleen was no felt, and no fluid wave was detected. No bruit was heard. The lower right leg was pale and cold below the calf, and the right posterior tibial and dorsalis pedis pulses were absent. The left foot was warm and the pulses were intact. An arterial blood gas measurement obtained which he was breathing room air showed a pH of 7.46, a partial pressure of CO2 of 34mmHg, and a partial pressure of O2 of 61 mmHg. A chest radiograph (Fig.1 ) demonstrated a pleural-based, wedge-shaped pulmonary infarction (Hampton’s hump) at left lung base. There was a focal avascularity (Westermark’s sign) in the right upper lung field. Transthoracic echocardiography revealed right ventricular dilatation and hypokinesia, with moderate tricuspid regurgitation and an estimated right ventricular systolic pressure of 55 mmHg. Doppler studies of legs showed proximal deep venous thrombosis in the right leg. A ventilation-perfusion scan showed normal ventilation images (not shown here) and loss of perfusion to the entire right upper lobe as well as to the anterior, lateral, and medial basal segments of left lower lobe (Fig.2). Multiple, small perfusion defects were also evident in the left upper lobe. Under the impression of pulmonary embolism, heparin was given since he arrived the ER. Seven days after he admitted in our hospital, the patient had multiple episodes of arterial desaturation and increasing oxygen requirement despite ongoing anticoagulation with heparin and intubation. The urgent chest CT scan showed a large embolus at the bifurcation of the main pulmonary artery, with extension into bilateral pulmonary arteries (Fig.3). After treatment with intravenous tissue plasminogen activator, the patient's respiratory status dramatically improved over a period of several hours, and approximately 24 hours later, the repeated echography showed that the right ventricular systolic pressure had decreased to 36 mmHg. He was treated with a heparin infusion for five days more, and followed by warfarin therapy. An extensive evaluation of the risk factors of hypercoagulabe state was also performed. There was no identified coagulation disorder. Repeated stool occult blood tests were positive, and panendoscopy was performed which showed a large gastric ulcer in the cardiac portion. The biopsy showed adenocarcinoma. Therefore, the patient subsequently received cancer staging, then operation and chemotherapy for gastric cancer. 繼續教育考題 1. (D) Which of the following test results would be highly useful in excluding the diagnosis of pulmonary embolism? A Normal PaO2 by ABG  B Absence of right heart strain on ECG C Intermediate probability of V/Q scan D  Normal plasma level of D-dimer by ELISA E Normal CT scan of the chest 2. (E) Which of the following hypercoagulable condition is possible underlying cause of patients who have pulmonary embolism? A Protein C or S deficiency B Bed ridden C Oral contraceptive D Malignancy (Trousseau's syndrome) E All of the above 3. (C) Which of the following statements regarding the diagnosis of DVT and pulmonary embolism is true?  A A diagnosis of PE would be incorrect in patient who presents with dyspnea and found to have leukocytosis B There is often no elevation of the alveolar-arterial difference in patients with acute PE who are otherwise normal C Pulmonary arteriography is the gold standard method for diagnosing PE D A chest X ray can generally diagnose or exclude PE E The sensitivity and specificity of ventilation-perfusion scan are low and limited its clinical usage 4. (B) Which of the following statements regarding therapy of PE is true? A Heparin-induced thrombocytopenia usually occur within 24 hours of onset of heparin therapy B Embolic obstruction of pulmonary artery resolves by 10 to 20 percent during the first 24 hr after acute PE C Thrombolytic therapy reduces the mortality of patients with PE when compared with heparin therapy alone D  The preferred therapy of fat embolism is heparin infusion 5. (C) True statements regarding the use of low molecular weight heparin (LMWH) in the management of venous thromboembolic disease include : A LMWH is not as effective and safe as continuous intravenous unfractionated heparin (UFH) in treatment of deep venous thrombosis (DVT) B  LMWH is much less cost-effective than UFH for treatment of DVT C  Bleeding complications are lower with LMWH D Heparin-induced thrombocytopenia is not a complication of LMWH E  LMWH is more effective than tPA in treatment in massive pulmonary embolism 6. (B) Which of the following pulmonary causes of chest pain most easily confused with myocardial infarction? A  Spontaneous pneumothorax B  Pulmonary embolism C Pneumonia D Pulmonary infarction E  Pleurisy 7. (C)  Normal (innocent) murmurs are usually which type of murmur? A Early systolic B Presystolic C  Midsystolic D  Holosystolic E  Early diastolic 8. (E)  Which of the following statement about PE is true? A  In many cases, the only finding on physical examination is an accentuation of P2 B Duplex scanning of the legs reveals evidence of prior venous thrombosis in 35 to 45 percent of patients with thromboembolic pulmonary hypertension C Depending the disease stage, the transthoracic echocardiography may demonstrate the variable degrees of RA and RV dilatation, TR, a leftward displacement of interventricular septum, etc. D  Normal CT scan could not exclude the possibility of PE. E All of the above 9. (B) Which of the following statement of PE is wrong? A  Right heart cath should be considered in any patient with unexplained dyspnea and segmental or larger defects on ventilation-perfusion scan, especially in patients with RV dysfunction B Pulmonary thromboendarectomy is considered in all patients who were diagnosed PE C  The location and extent of the proximal thrombolic obstruction are the most critical determinants of operability D  Lifelong anticoagulation therapy is strongly recommended after thromboendarectomy E  Residual pulmonary hypertension and RV dysfunction might be noted after thromboendarectomy 10. (D)  Which of the following statement of PE is wrong? A  The response to thrombolytic therapy is better in acute PE, and could be considered in patients with progressively respiratory distress B  The extent of vascular obstruction is a major determinant of pulmonary hypertension, and more than 40% of obstruction is noted in the most patients who were diagnosed to have PE C Without intervention, the rate of survival is low and proportional to the degree of pulmonary hypertension at time of diagnosis D  The ventilation scan is still indicated even in the completely normal perfusion scan E  Evaluation of underlying disease is important when PE is diagnosed 答案解說 D-dimer by ELISA是一sensitive marker，正常時可排除PE的診斷。其他都不一定。 PE可能原因很多，只要可能引起hypercoagulable condition均可能，然而也有部份病人並不能找出任何原因，此時，仍需定期追蹤。 (A) Although a patient who presents with dyspnea and is found to have leukocytosis most likely has pneumonia, acute PE can occur in this setting. The presence of pneumonia dose not exclude the possibility of concomitant PE. (B) In acute PE, the alveolar-arterial difference is usually elevated. Pulmonary arteriography is the gold standard method for diagnosing PE. (D) A chest X ray cannot used definitely diagnose or exclude PE. (E) The ventilation-perfusion scan is good non-invasive diagnostic tool in PE. (A) Heparin-induced thrombocytopenia 多於使用6至12日後出現。 (C) Thrombolytic therapy is potentially most useful in a small group of patient with documented massive pulmonary embolism with severe hemodynamic compromise. Except for this situation, tPA has not reduced the mortality when compared with heparin alone. (D) Fat embolism用heparin並無助益，最重要的是氧氣治療。 LMWH的優點：(1) 皮下注射，較方便，(2) more stable levels of anticoagulation，(3) 不需抽血監測。A meta-analysis of randomized trials comparing LMWH with UFH in patients with DVT showed that LMWH reduced the mortality rate by 29% over 3 to 6 months of follow-up ,and reduced bleeding complication by 43%. Furthermore, therapy with LMWH proved to be highly cost-effective compared with UFH because of the reduced need for blood test monitoring and could be used as outpatient therapy. The drug has approved for inpatient therapy of DVT with/without PE by FDA. The clinical presentation of PE is non-specific, and later in the course of the disorder, chest pain on exertion, presyncope or syncope may occur as a result of severe pulmonary hypertension and RV failure. The characteristics of chest pain sometimes are difficult to differentiate from the myocardial ischemia. Normal systolic murmurs are related to intracardiac flow rates and are usually loudest in midsystole. 以上皆是 (B) Pulmonary thromboendarectomy is considered in symptomatic patients who have hemodynamic or ventilatory impairment at rest or with exercise.  (D) PE的病人，其Ventilation-perfusion scan出現one or more mismatched, segmental or larger defects可作為診斷，而正常之ventilation scan 並不能排除此診斷。