Embed Size (px)
2. 3. Q;3,A 45-year-old woman is evaluated in the emergency department because of the sudden onset of shortness of breath and chest tightness earlier this afternoon. She has been in excellent health and returned 2 days ago from a trip to Japan. On physical examination, her pulse rate is 116/min and respiration rate is 36/min. Cardiopulmonary examination is otherwise unremarkable, and a chest radiograph shows no infiltrates. Measurement of arterial blood gases on room air shows the following: pH 7.48, Paco 224 mm Hg, and Pao 278 mm Hg; oxygen saturation is 96%.
5. Asymptomatic PE in DVT pts
6. Of an estimated 200,000 deaths per year in the United States, only 13,000 (6%) occur in patients who have received treatment. The vast majority of patients (94%) who die of pulmonary embolism do not receive treatment because the diagnosis is not made 7. PE
8. Q;3,A 45-year-old woman is evaluated in the emergency department because of the sudden onset of shortness of breath and chest tightness earlier this afternoon. She has been in excellent health and returned 2 days ago from a trip to Japan. On physical examination, her pulse rate is 116/min and respiration rate is 36/min. Cardiopulmonary examination is otherwise unremarkable, and a chest radiograph shows no infiltrates. Measurement of arterial blood gases on room air shows the following: pH 7.48, Paco 224 mm Hg, and Pao 278 mm Hg; oxygen saturation is 96%.What is the most appropriate immediate next step in this patientsmanagement? ( A ) Pulmonary angiogram ( B ) Compression ultrasonography of the lower extremities ( C ) Therapy with diazepam ( D ) Intravenous heparin ( E ) Ventilation-perfusion lung scan 9. Q:3, Ans=D, When venous thromboembolism is strongly suspected, the first action taken should be to administer heparin in a therapeutic dose (in the absence of contraindications to anticoagulation) to prevent new clot formation, allow unopposed fibrinolytic activity to facilitate thrombus resolution, and avoid progression into the pulmonary circulation. Therapy should be started before performing confirmatory diagnostic tests such as a ventilation-perfusion scan, pulmonary angiogram or compression ultrasonography of the lower extremities. Subtherapeutic or delayed anticoagulation is associated with unacceptable recurrence rates of venous thromboembolism, and is a common error in the initial phases of treatment. Although relatively less heparin is required to prevent the coagulation cascade from being initiated, more is required after the cascade is under way. Therefore, early administration of an adequate dose is required. For continuous infusions, the activated partial thromboplastin time should be monitored regularly to ensure that the dose is therapeutic. Inadequate initial heparin therapy also has been associated with late recurrences of thromboembolism. Anxiolytic therapy would not be an appropriate as the initial step in this patients manageme 10. Virchow`s Triad
11. 12. Acquired Risk Factors for VTE
13. 14. 15. Factor V Leiden and VTE
16. 17. Natural history
19. P.E.: physiology
20. PHTN after first episode of PE
21. Q-9:52 yr woman, 1 yr h/o dyspnea. Heavy smoker in past, h/o HTN.O/E loud P2, elevated JVP,mild bilat ankle edema. CBC, Chem-panel, HIV, ANA , Rh. Titer negative. CXR: prominent Pulm. Arteries, echo: normal EF, RVE, PA-syst pressure 60, PFTs: normal volumes, DLCO 40% pred, V/Q: mild heterogeneity of perfusion, Swan Ganz: RAP 10, RVP 50/10, PAP 50/20, PAOP 26, CI 2. ?DX
22. A-9=A 23. DVT: Clinical diagnosis ?
24. Fedullo and Tapson, NEJM, 9-25-03 25. Fedullo & Tapson, NEJM 9-25-03 Low=10%, Inter=30% and High=>70% 26. From JAMA 1/11/06 27. Prediction of PE in ED. by Gal et al, AIM 7 Feb 2006 28. 29. DVT
30. Venogram: Popliteal Vein Thrombosis 31. Compression ultrasound (Goldhaber) Artery compressed, but vein did not: DVT 32. 33. CUS in suspected PE?
34. MRI in Dx Of DVT
35. Pelvic DVT diagnosis by MRA
36. Pulmonary Embolism, NEJM 7-9-98 37. Goldhaber, NEJM 7-9-98 38. SYMPTOMS AND SIGNS IN 117 PATIENTS WITH ACUTE PULMONARY EMBOLISM WITHOUT PRE-EXISTING CARDIAC OR PULMONARY DISEASE (Stein, Chest 1991) 30 TACHYCARDIA>100 37 COUGH 1 CYANOSIS 3 THIRD H.S. 3 PLEURAL RUB Common in PE 4 RIGHT VENR. LIFT *= Significantly More 4 HOMAN`S SIGN 5 WHEEZES 7 TEMP. >38.5*C 4 ANGINA 11 DIAPHORESIS 9 WHEEZING 11 DVT 10 PALPITATIONS 23 LOUD P2 * 13 HEMOPTYSIS 24 FOURTH H.S. * 28 LEG SWELLING 51 RALES (CRACKLES) * 66 PLEURITIC PAIN 70 TACHYPNEA >20/min 73 DYSPNEA % OF PATIENTS SIGNS %OF PATIENTS SYMPTOMS 39. 40. 41. During fibrinolysis of fibrin, plasmin cleaves factor XIIIacross-linked fibrin into an array of intermediate forms. The D-dimer and E fragments are the result of terminal fibrin degradation.,P.Bockenstedt, NEJM 9-25-03 42. Plasma D-Dimer
43. D-Dimer in diagnosis of VTE: AJRCCM, Feb 2002; 345-8
62. Spiral CT in PE
63. Spiral cat scan in a patient with massive saddle Pulm. Embolism, before and after thrombolytic Rx with TPA. NEJM, 10-10-02 64. Three advantages of helical CT deserve mention. 1,The value of CT's ability to identify an alternative diagnosis in up to a third of patients with suspected PE2, As with lung scanning, when the combination of pretest probability and helical CT results yield sufficiently high or low post-test probabilities, the test obviates the need for conventional angiography and its associated higher morbidity.3, In practice settings in which clinicians can obtain a CT scan more quickly than a lung scan or an angiogram, the use of CT may prevent delays in therapy Matthew B. Stanbrook, MDBrigham and Women's Hospital,Harvard Medical School 65. CT scan in P.E. Isolated thromboembolism of the subsegmental pulmonary arteries is not unusual, occurring in 6 to 30 percent of patients with embolism in different series. Filling defects involving the main or lobar pulmonary arteries can be considered diagnostic of embolism, whereas a normal CT scan may indicate a substantially reduced likelihood of embolism but cannot be used to rule out the possibility of embolism with the same degree of certainty that a negative ventilationperfusion scan provides. Outcome studies have demonstrated that withholding anticoagulant therapy in patients with a negative CT scan coupled with a negative ultrasonographic study of the legs is a safe strategy, except in those patients who present with a high clinical probability of embolism Fedullo and Tapson, NEJM 9-25-03 66. Role of D-dimer, Clinical Prediction and Spiral CAT scan: Christopher study, JAMA 1/11/2006
67. CT chest and PE
68. Should CAT scan of chest be accompanied by US of legs to rule out VTE?
69. How long does it take to resolve PEs?
70. Left pulmonary artery filling defect in PE. (Murray and Nadel) 71. Pulmonary Angiography: PIOPED data
72. Indications for Pulmonary Angiogram
73. Echocardiogram in pulmonary embolism:Goldhaber, NEJM 7-9-98 74. Echocardiogram in PE
75. Fedullo and Tapman, NEJM 9-25-03 76. Fedullo & Tapman, NEJM 9-25-03 77. Fedullo and Tapman NEJM 9-25-03 Note: low clinical prob + low prob V/Q may stop workup 78. Fedullo and Tapman NEJM 9-25-03 79. Q-10: A 52 yr man c/o mild dyspnea and chest pain after carrying light luggage from car following a 9 hr drive. Has h/o COPD, PUD and Hodgkins Lymphoma in remission x 4 yr after radioRX. Auto-Accident 1 yr ago, had R leg DVT, Rx Heparin x 5 D, then coumadin x 3 mo.,P/E, EKG, CXR: unremarkable, V/Q: low probability. ? Next in DX test
81. Treatment for PE
82. Bed rest in DVT and PE patients
83. Heparin and PE
84. 85. Cumulative Probability of Recurrent Venous Thromboembolism in Patients with a Second Episode, According to the Duration of Assigned Anticoagulant Therapy.Schulman et al, NEJM 2-6-1997 86. Duration of Anticoagulation During therapy with vitamin K antagonists, the risk of recurrence is very effectively reduced by approximately 90 percent, to 0.7 episode per 100 person-years. In the 6 to 12 months immediately after the discontinuation of therapy, a catch-up phenomenon occurs, resulting in an absolute incidence of recurrence of venous thromboembolism of 5 to 10 percent. This phenomenon has been observed after 3, 6, and 12 months of vitamin Kantagonist therapy and therefore suggests that prolonging this therapy simply delays recurrence until the therapy is stopped, rather than reducing the risk of recurrence.During the subsequent years, the risk of recurrence stabilizes, and the annual incidence of recurrence is 1 to 2 percent. Buller and Prins,NEJM 8-14-03 87. Bates and Ginsberg, NEJM 7-15-04 88. 89. What Intensity of Anticoagulation ? low-intensity anticoagulant therapy (INR 1.5 to 1.9) reduces the risk of recurrent thrombosis by about 75 percent, whereas conventional-intensity therapy (INR 2 to 3) reduces this risk by over 90 percent, and no increase in major bleeding ( kearon et al NEJM 8-14-03) 90. Q;2; A 76-year-old woman with metastatic breast cancer is evaluated because of a 3-day history of swelling of her right leg and pleuritic chest pain. Ultrasonography shows an occlusive thrombus in the femoral vein. Results of a ventilation-perfusion scan are normal, and therapy with continuous intravenous heparin is begun. On the fourth day of heparin therapy and after oral warfarin has been started, the activated partial thromboplastin time is therapeutically prolonged, but the prothrombin time has not yet reached the therapeutic range; at this time, the patient develops dyspnea.On physical examination, her blood pressure is 140/90 mm Hg; she is tachypneic and tachycardic, but the remainder of her cardiopulmonary examination is normal. Chest radiograph shows no abnormalities. Measurement of arterial blood gases reveals new hypoxemia on room air. Ventilation-perfusion scan shows perfusion defects in the entire right lower lobe and the inferior subsegment of the lingula. 91. Q;2 continued
92. Q;2Answer is B
93. Venacaval Interruption
94. Urokinase Pulmonary Embolism Trial(UPET)
95. Thrombolytic in PE
96. FDA approved thrombolytic regimens for PE
97. Thrombolytic Rx in Pulm.Embolism NEJM, 10-8-02 MethodsWe conducted a study of patients withacute pulmonary embolismandpulmonaryhypertension or right ventricular dysfunction but without arterial hypotension or shock. The patients were randomly assigned in double-blind fashion to receive heparin plus 100 mg of alteplase or heparin plus placebo over a period of two hours. The primary end point was in-hospital death or clinical deterioration requiring an escalation of treatment, which was defined as catecholamine infusion, secondary thrombolysis, endotracheal intubation, cardio pulmonaryresuscitation, or emergency surgical embolectomy or thrombus fragmentation by catheter 98. Thrombolytics in submassive P.E.
99. 100. Chart review by Anderson, % of hospitalized patients who received DVT prophylaxis
101. Q-11: 32 yr BM, 4 mo h/o progressive dyspnea on exertion. P/E High JVP, Large V waves in neck, Holosystolic M at L lower parasternal area. Mild ascitis and bilateral mild ankle edema. High resolution CT shows mosaic perfusion. FVC=83%, FEV1/FVC=75%, TLC=76%,RV=73%, DLCO=22% . ? DX
102. A-11=3 103. Q:1A 63-year-old woman is scheduled to undergo a total knee replacement and needs prophylaxis for deep venous thrombosis. She has no previous history of increased bleeding or of a hypercoagulable state. She takes aspirin, 325 mg/d, for primary prevention of cardiovascular disease and wants to continue taking it; she does not want subcutaneous injections
104. Q :1,Ans:D Warfarin is recommended for prophylaxis for deep venous thrombosis in patients undergoing total knee replacement. There are several regimens for starting prophylaxis in the perioperative period, including one tablet on the night before surgery, or starting with the first dose on the first day after surgery. The target INR is between 2 to 3.Although subcutaneous low-molecular-weight heparin in prophylactic doses is a reasonable alternative to warfarin in this setting, full-dose intravenous unfractionated heparin is not recommended. Total knee replacement surgery carries a risk of calf deep venous thrombosis of 40% to 80%, a risk for proximal deep venous thrombosis of 10% to 20%, a risk for clinical pulmonary embolism of 5% to 10%, and a risk for fatal pulmonary embolism of 1% to 5%. Aspirin is not effective for prophylaxis of deep venous thrombosis. The patient should stop taking aspirin 7 days before this procedure to reduce the risk of bleeding complications. Elastic stockings and pneumatic compression are additive for prophylaxis, but are not sufficient for effective prophylaxis in themselves. 105. Q;4,A 75-year-old man comes to the emergency department because of a 2-day history of a swollen and tender left calf following a 10-hour automobile trip. Ultrasonography confirms the presence of a deep venous thrombosis of the left calf extending to the popliteal region. The patient has an extensive smoking history, but his medical history is otherwise unremarkable. Physical examination is normal, and a stool specimen is negative for occult blood. The complete blood count, prothrombin time, activated partial thromboplastin time, and routine serum chemistry studies are normal.
106. Q4,Ans=A. Deep venous thrombosis, particularly in an elderly patient, always raises concern about an underlying neoplasm. Although such patients may have an increased incidence of occult malignancy, several studies have demonstrated that an extensive search for a neoplasm rarely yields positive results. A neoplasm amenable to curative therapy is found even more rarely. Therefore, a nondirected and extensive evaluation of this patient for occult malignancy is very unlikely to identify a treatable neoplasm and is not cost effective. However, any clues obtained from the H & P (including a digital rectal examination) suggestive of a neoplasm should be pursued. In this patient, the extensive smoking history justifies a screening CXR despite the lack of symptoms. Since the patient has no other complaints or findings suggestive of an underlying neoplasm (weight loss, stools positive for occult blood, abdominal pain). Therefore, a more extensive evaluation is not indicated. Measurement of the serum carcinoembryonic antigen level may be useful in following the progression of colon cancer once a diagnosis and baseline CEA levels are established but is not sensitive or specific when used as a screening assay. 107. Q;5 ,A 38-year-old man is receiving warfarin therapy for treatment of a deep venous thrombosis of the left leg that he developed 3 weeks ago. He comes for his scheduled prothrombin time INR determination. He denies gingival bleeding, hematuria, nosebleeds, or gastrointestinal disorders but reports a sore throat and fever that started about 1 week ago. He has not been able to swallow and has consequently been on a mostly clear liquid diet for the last week.On physical examination, his temperature is 38.0 C (100.4 F). His posterior pharynx is erythematous but without exudate. There are several scattered ecchymoses on the forearms and legs. The remainder of the examination is normal.The laboratory evaluation reveals a hematocrit of 41%; activated partial thromboplastin time of 37 s; and a prothrombin time INR of 6.0. 108. Q; 5 continued
109. Q:5, A=B ,This patient has a supratherapeutic INR. The ecchymoses are a minor bleeding complication, but he has a normal hemoglobin level and no evidence of more serious bleeding. The deep venous thrombosis of the left leg is relatively new, and he is at risk of further propagation of the clot if anticoagulation is not maintained. This patient therefore needs to have the warfarin effect lowered without fully reversing the anticoagulation. Vitamin K therapy will correct the INR without the risk associated with transfusing a blood product. Additional vitamin K overrides the warfarin blockade of the -carboxylation pathway and results in production of functional clotting factors within hours. The dose of vitamin K determines how much of the warfarin effect will be reversed. A dose of 5 mg of vitamin K will significantly reverse the anticoagulant effect of warfarin within 12 to 24 hours if the patient has good liver function. A 10-mg dose will usually block the warfarin effect completely and interfere with attempts to resume anticoagulation with warfarin. The risk of clotting versus the risk of bleeding determines how much vitamin K to give and how long to withhold the warfarin dose. 110. Q=5 A=B, continued For patients such as the one described, the dose of vitamin K should be low enough to allow resumption of anticoagulation with warfarin as soon as the INR has dropped into the therapeutic range. Studies have shown that vitamin K, 1 to 2 mg subcutaneously or 2.5 mg orally, will bring the INR into the therapeutic range without causing overcorrection. Low-dose vitamin K should decrease this patients INR without placing him at risk for another thrombosis.Fresh frozen plasma is the most rapid way to replace vitamin K clotting factors and reverse the anticoagulation. However, because of the infectious and allergic risks associated with blood products, fresh frozen plasma is only used to reverse warfarin if a patient has a serious bleeding complication or excessive risk of bleeding. Therefore, giving this patient fresh frozen plasma places him at greater long-term risk than the immediate risk imposed by the excessive anticoagulation.Intramuscular medications should not be given to patients with a coagulopathy because these patients have a high risk of developing an intramuscular hematoma. Furthermore, bleeding into the muscle will hamper attempts to resume anticoagulation for the underlying thrombosis. This patient's poor oral intake over the last several days will result in low vitamin K stores. Stopping the warfarin with no other therapy (that is, without replacing vitamin K) will result in a slow reversal of the anticoagulant effect and prolong the risk of bleeding. 111. Q:6, A 23-year-old otherwise healthy woman has a pulmonary embolism while hospitalized after a motor vehicle accident. She is 8 weeks pregnant. She has completed 1 day of therapy with unfractionated heparin.
112. Q;6, Ans:B
113. Q;7,A 24-year-old man is evaluated because of a swollen right calf. The calf has been swollen for 1 day. He had a deep venous thrombosis of the opposite leg when he was 17 years old, for which he took warfarin for 3 months. He has never smoked cigarettes. His father also had a deep venous thrombosis, but he is currently in good health. Physical examination shows a tender, swollen, right calf. Doppler studies confirm a deep venous thrombosis.
115. Hemorrhage occurs in up to 7 percent of patients during initial treatment; the risk is affected by the heparin dose, the patient's age, and concomitant use or nonuse of thrombolytic and antiplatelet agents. Long-term use of heparin (i.e., longer than one month) can cause osteoporosis. 26 , 27 , 28Heparin-induced thrombocytopenia is immune-mediated and in 30 to 50 percent of cases is associated with venous or arterial thrombosis. 26Patients with previous heparin-induced thrombocytopenia should receive alternative anticoagulant agents, such as danaparoid, lepirudin, or argatroban. 26 NEJM 7-15-04 116. Dalen, Chest, Nov 2002 Mortality of Untreated PE (Clinical Diagnosis)3035 Composite 30 1963 Morrell et al 6 35 1961 Hermann et al 5 32 1946 Zilliacus 4 1825 1969 Coon et al 3 38 1960 Barritt and Jordan 2 Mortality, % Year Source 117. Dalen, Chest Nov 2002 When to Treat for VTEDiagnosis of DVT by venogram, compression ultrasound, or impedance plethysmography. Echocardiographic diagnosis of clot in main pulmonary artery, right pulmonary artery, or left pulmonary artery, and right ventricular dilatation. Echocardiographic diagnosis of intracardiac thrombus. Positive pulmonary angiogram, positive chest CT, or high probability V/ Q scan. 118. Dalen, Chest Nov 2002 When to Withhold Therapy for Suspected PE Normal chest CT finding IndeterminateV/Qscan, or Normal compression ultrasound legs, or Normal d-dimer, or Low clinical probability of PE plus: Normal pulmonary angiogram or normal perfusion scan findings 119. Treatment of VTEColumbus Investigators, 281997 Simonneau et al, 271997 Thery et al, 251992 For PE Hull et al, 211992; Prandoni et al, 261992 Holm et al, 201986 For DVT Low-molecular-weight heparin, subcutaneous None Greenfield et al, 191971 Embolectomy, catheter Decousos et al, 181998 Mobin-Uddin et al, 171969 IVC filter by catheter rt-PA trials, 23 24199098 Bounameaux et al, 161985 rt-PA UPET, phase 2, 221974 Browse and James, 151964 Streptokinase UPET, 141973 Hansen et al, 131961 Urokinase Thrombolytic agents None Collins et al, 121943 IVC ligation Trial Study Group, 741995 Duration of anticoagulant Allen et al, 721947 Oral anticoagulants Barritt and Jordan, 21960 Murray and Best, 91938 Unfractionated heparin None Homans, 81934 Femoral vein ligation None Trendelenburg, 71908 Surgical embolectomy First Randomized Controlled Trial First Clinical Report Treatments 120. Dalen, Chest, Nov 2002 Incidence of Shock in Patients With PE Documented byPulmonary Angiography9.3 753 Totals 6 129 UKEP, 431987 10 313 Greenfield and Langham, 421984 13 144 Alpert et al, 401976 7 167 UPET, 221974 With Shock, % Patients, No. Source 121. Mortality of Angiographically Documented PE With Shock 35 193 Totals 33 rt-PA 24 Gulba et al, 451994 30 Catheter embolectomy 46 Greenfield et al, 391993 20 rt-PA 15 Diehl et al, 441992 42 Embolectomy 78 Meyer et al, 361991 32 Anticoagulation and/or IVC interruption 19 Alpert et al, 401976 18 Heparin, with or withouturokinase 11 UPET, 141973, UPET, 22 Mortality, % Treatment no Source 122. Ximelagatran in VTE JAMA 2005; 293:681-89