Case Discussion A 59 year-old man suffered from persistent chest pain for 14 hours Brief History This 59 year-old man is a case of hypertension noted for 20 years without regular control. He suffered from intermittent precordial discomfort for about one year. It was located over precordial area with radiation to back and was associated with cold sweating. The symptom could be triggered by exercise and be relieved by resting. In recent one month, the frequency of chest pain increased. He suffered from persistent chest pain at 2 am on June 13, 2000 with little improved by sublingual nitroglycerin. On consulting our ER that morning, ECG showed old inferior wall myocardial infarction and inverted T over III, V4-6. Cardiac enzyme elevation was also noted. Echocardiography at ER showed hypokinesia over posterior, inferior, lateral, and apical regions with LVEF about 20 %. Intravenous nitroglycerin was administered but chest pain persisted. Under the impression of acute non-Q MI, he was admitted to our CCU for further evaluating and management. Physically, he was illness looking in general with clear consciousness. Blood pressure was 132/72 mmHg. Pulse was regular at the rate of 86/ min. Body temperature was 36.6 °C. Respiratory rate was 20 /min. Conjunctiva was not pale. Sclera was not yellowish. Neck was supple without jugular vein engorgement, carotid bruit, or lymphadenopathy. The chest wall was symmetric without deformity. On auscultation, there were bilateral basal crackles and mild wheezing. A grade II/VI pan-systolic grade murmur was noted over left sternal border and apex with radiation to axilla. There was no gallop nor opening snap. Liver was palpable about 1 finger below right cost margin. No abdominal tenderness or rebound pain was noted. There was no leg pitting edema. Peripheral pulses were symmetric. Laboratory Findings: 1. CBC :   WBC  (/μl) Hb  (g/dl) MCV  (μl) Plt  (k/μl) Ret  (%) 6/13 7570 10.8 91 221 1.44 2. BCS:   Alb/Glo  (g/dl) Bil(T/D)  (mg/dl) ALP  (U/l) GOT/GTP  (U/l) r-GT  (U/l) LDH  (U/l) BUN/Cr  (mg/dl) TG/Chol (mg/dl) 6/13 3.3/3.1 0.7/0.2 131 138/39 39 1045 23/1.6 183/176 LDL-C : 103, HDL-C : 36 mg/dl 3. Electrolyte:6/13 Na: 138 mM; K: 3.3 mM; Ca: 2.15 mM 4. Others : Ferritin: 65.3, Iron : 48, TIBC : 270; HbA1C : 5.3 %; 24 hr CCr : 67 ml/min 5. PPT: Heparin(U/d) : 15000(D1-2) 30000(D2-6) 35000(D7-8) PPT : 39.1/37.8 38.3/38.6 60/32.4 TT : unclot 6. ECG : III, aVf Q wave, V4-6 inverted T wave, suggesting old inferior wall infarction and lateral wall ischemia 7. EChocardiography : Dilated LV with regional wall motion abnormalities over 3 vessels territories, esp. right and left circumflex regions. LVEF 0.20 (by area length). Dilated ascending aorta. Mild MR. Clinical Course & Treatment :      After admission, nitroglycerin was titrated till chest pain relief. However, the PTT was refractory despite increasing heparin dosage upto 35,000 U per day. TT showed unclot. Low molecular weight heparin (Fractionated heparin) was used since 6/20 in place of heparin. Dobutamine (2.7 μg/kg/min), diuretics and ACE-inhibitor were used. Iron was supplied for IDA. Gouty pain was controlled by anti-inflammatory agent. Amiodarone was used for frequent VPC. Stress echocardiography showed ischemic myocardium over left circumflex area. The schedule for percutaneous balloon coronary angioplasty was postponed by hematemesis which occurred on 6/21 morning. 繼續教育考題 1. (A) Which of the following factors is most sensitive to heaparin? A Factor IIa B Factor IXa C Factor Xa D None of them 2. (B) What is the parameter to titrate heparin dosage in acute coronary syndrome? A PT B PTT C Bleeding time D Platelet count 3. (B) What is the potential mechanism that makes the PTT refractory to heparin infusion in this patient? A Patient has antibody against heparin B Patient has acute reactive protein such as factor VIII which binds to unfractionated heparin C Patient is in a hypercoagulation state D The heparin is of bad quality 4. (D) When should we suspect heparin overdose in a case with poor prolongation of PTT during heparin infusion (“Heparin resistant”)? A Daily heparin dose over 5,000 units B Daily heparin dose over 10,000 units C Daily heparin dose over 20,000 units D Daily heparin dose over 30,000 units 5. (C) How to confirm the diagnosis of heparin overdose? A PT > 2X of control B PTT > 1.5X of control C TT > 3 min D Platelet counts < 100,000/Cmm 6. (D) Which of the following statements regarding low molecular weight heparin (LMWH) is correct? A  LMWH has reduced ability to inactivate IIa, B LMWH has reduced binding to acute reactive protein C LMWH has lower incidence of platelet dysfunction D All of the above 7. (A) Which one of the following statements regarding the usage of low molecular heparin is correct? A Dalteparin (Fragmin) 2,500~5,000 units/day subcutaneous injection B Dalteparin (Fragmin) 2,500~5,000 units/day intramuscular injection C Nadroparin (Fraxiparin) 5,000 units intramuscular injection D None of the above 8. (D) How should we adjust LMWH if major bleeding noted? A Discontinue LMWH. B Resume LMWH if no more bleeding noted for at least 8 hours and decrease dosage to half. C So far there is no objective monitor parameter for LMWH D All of the above 9. (D) What is the appropriate time for coronary intervention in this patient ? A If the chest pain persists despite medical control B If stress thalium-201 perfusion scan shows adequate ischemic tissue that can be rescued by PTCA C If stress echocardiography shows adequate ischemic tissue that can be rescued by PTCA. D All of the above 10. (B) What is the target for PTCA? Why? A Left anterior descending artery, because echocardiograpy shows apical wall motion defect. B Left circumflex, because stress echo shows ischemic tissue over lateral wall. C Right coronary artery, since ECG shows old inferior wall infarction. D None of the above

答案解說

1. Binding with ATIII → inactivate IIa, Xa, IXa , but IIa is most sensitive 2. Keep PTT prolong about 1.5~2.0 x of normal value 3. Unfractionated heparin (UFH) may bind to many kinds of serum protein including factor VIII which may elevated as acute phase reaction to ischemia and decreases the magnitude of PTT prolongation. Since IIa is most sensitive to heparin, TT which assesses IIa will prolong even in the presence of acute phase reactive protein. Patient will have bleeding tendency. 4. When either heparin dosage is over 30000 units/day without PTT significant prolongation or in a case with bleeding tendency such as ecchymosis. 5. Check thrombin time (TT). If TT prolongs over 3 minutes, the heparin dosage is over.  6.  LMWH has reduced ability to inactivate IIa, reduced binding to protein, platelet, and endothelial cells, thus decrease the incidence of platelet dysfunction and vessel permeability. LMWH is superior to placebo and UFH in reducing ischemic events or death in the acute phase of unstable angina or non-Q infarction. 7. MWH, subcutaneous injection 8. Discontinue LMWH. Resume LMWH if no more bleeding noted for at least 8 hours and decrease dosage to half. So far there is no No objective monitor parameter for LMWH. 9. If the chest pain persists despite medical control or if stress thalium-201 perfusion scan or stress echocardiography shows adequate ischemic tissue that can be rescued by PTCA. 10. In this patient, dobutamine stress echo showed left circumflex territory is under ischemic condition.