Case 1: Pregnant patient with chest pain
A 26-year-old woman who is 20 weeks pregnant is hospitalized for acute shortness of breath with mild pleuritic chest pain. Her chest radiograph is clear. She has no pertinent past medical history.
Which of the following would be the best management of this patient?
A. Oral warfarin for the duration of the pregnancy and discontinue anticoagulation postpartum
B. Low-molecular-weight heparin for the duration of the pregnancy and discontinue anticoagulation postpartum
C. Unfractionated heparin for the duration of the pregnancy and discontinue anticoagulation postpartum
D. Intravenous thrombolytic therapy
E. Unfractionated heparin or a low-molecular-weight heparin and continue anticoagulation postpartum.
Case 2: ED patient with dyspnea and cough
A 46-year-old man is evaluated in the emergency department with a one-day history of progressive dyspnea and nonproductive cough. He does not have hemoptysis, chest pain, or leg discomfort and has no personal or family history of cancer or clotting episodes. He had outpatient ophthalmologic surgery under local anesthesia last week. His medical history includes mild asthma and impaired glucose tolerance, which is controlled by diet. His only medication is a topical optic analgesic.
On physical examination, he is dyspneic and appears anxious; the temperature is 37.6°C (99.8°F), blood pressure is 150/89 mm Hg, heart rate is 110 beats/minute, and respiration rate is 24 breaths/minute. Cardiac examination discloses tachycardia without murmurs or gallops or evidence of jugular venous distention. Examination of the lungs discloses faint bilateral expiratory wheezes, without rhonchi or rales; the hemi-diaphragms descend normally during inhalation. The abdomen is normal. Extremities are not swollen and are nonedematous, nontender, and not cyanotic.
Chest radiograph is normal; an electrocardiogram shows tachycardia. Measurement of arterial blood gases with the patient breathing room air show a Po2 of 93 mm Hg, a Pco2 of 36 mm Hg, and a pH of 7.45. The D-dimer level is 200 mg/dL (normal <250 mg/dL).
Which of the following would most effectively determine the clinical likelihood of this patient's having a pulmonary embolism?
A. Obtaining the report of the patient's ophthalmologic surgery
B. Measuring hemoglobin A1c
C. Determining the effect of bronchodilators on the patient's signs and symptoms
D. Repeating D-dimer after one therapeutic dose of low-molecular-weight heparin
Case 3: Diabetic patient with confirmed PE
A 67-year-old man is diagnosed with pulmonary embolism. He has significant atherosclerotic vascular disease and a 10-year history of type 2 diabetes mellitus. Laboratory tests on admission show the following: hematocrit, 30%; sodium, 128 mEq/L (128 mmol/L), potassium, 5.5 mEq/L (5.5 mmol/L), glucose, 200 mg/dL (11.1 mmol/L); creatinine, 2.8 mg/dL (247.58 µmol/L); aspartate aminotransferase, 60 U/L; and alanine aminotransferase, 72 U/L.
Which of the following agents would require drug monitoring and possible dosage adjustment in this patient?
C. Tissue plasminogen activator
Case 4: Traveler admitted to the ED with chest pain
A 45-year-old man is evaluated in the emergency department for acute shortness of breath with right-sided chest pain. He also has a dry cough with scanty blood streaking of his phlegm. He is a nonsmoker and has no other past medical illnesses; he has just returned by airplane from Japan.
On physical examination, his temperature is 37.4°C (99.4°F), blood pressure is 102/76 mm Hg, pulse rate is 98 beats/minute, and respiration rate is 32 breaths/minute. Breath sounds are marginally decreased on the right side with vocal fremitus. There are no rhonchi. The pulmonary component of the second heart sound is accentuated. He feels soreness in the left calf and has trace left ankle edema. All peripheral pulses are intact.
Compression ultrasonography of the lower extremities is positive for the presence of deep venous thrombosis. A follow-up spiral CT scan of the chest confirms the presence of pulmonary emboli and a small right-sided pleural effusion. The patient is hospitalized and therapy with fractionated heparin and warfarin is started. On day three, the prothrombin time is 14.7 seconds and the INR is 1.6. Chest radiograph at this time shows a stable right-sided pleural effusion occupying about one-fourth of the right hemithorax.
Ultrasound-guided aspiration of the right pleural effusion is performed. The erythrocyte count is 100,000 cells/µL (100 × 109 cells/L), and the leukocyte count is 465 cells/µL (0.465 × 109 cells/L) with 70% neutrophils, 25% lymphocytes, 2% mesothelial, and 3% eosinophils. Total protein is 3.5 mg/dL (35 g/L), lactate dehydrogenase is 400 U/L, glucose is 75 mg/dL (4.16 mmol/L), and pH is 7.45. Gram stain of pleural fluid shows no organisms.
Which of the following is the most appropriate next step in management?
A. Discontinue heparin, continue warfarin
B. Discontinue warfarin
C. Continue warfarin and heparin until INR is therapeutic, and then discontinue heparin
D. Discontinue both heparin and warfarin
E. Place an inferior vena cava filter
Case 5: Young man with shortness of breath
A previously healthy 24-year-old man is evaluated in the emergency department after he develops shortness of breath four days into a cross-country automobile trip. A ventilation/perfusion scan shows unmatched perfusion defects in his right lower lobe and left lower lobe, accounting for about 25% of total perfusion. He is hospitalized and treated with intravenous heparin and warfarin.
One week later, the symptoms have resolved, and the INR is in the 2.0 to 3.0 range for two consecutive days. However, a repeat ventilation/perfusion scan shows persistent localized perfusion defects, accounting for about 20% of total perfusion.
Which of the following is the most appropriate next step in the management of this patient?
A. Continue inpatient with low-molecular-weight heparin
B. Discharge on warfarin
C. Measure pulmonary artery pressures during exercise
D. Perform factor V Leiden mutation assay
E. Perform CT angiography
Case 6: New mother with dyspnea and dizziness
A 23-year-old woman develops dyspnea and dizziness two days after a normal spontaneous vaginal delivery of a healthy child. Her urine output has been less than 20 mL/h for the past three hours. On physical examination, the temperature is 37.2°C (99.0°F), blood pressure is 80/60 mm Hg, heart rate is 125 beats/minute, and respiration rate is 22 breaths/minute.
The lungs are clear to auscultation. Cardiac examination reveals a fixed split S2, and jugular venous distention. The abdomen and pelvis are soft and nontender. After infusion of 1,500 mL of 0.9% saline, the blood pressure is 98/67 mm Hg and the heart rate is 105 beats/minute; the patient produces 80 mL of urine over the next hour.
A ventilation/perfusion scan shows large unmatched perfusion defects corresponding to the entire right lower lobe, half of the right middle lobe, and the entire left lower lobe. An echocardiogram shows evidence of right ventricular strain. A lower-extremity ultrasound shows a noncompressible left superficial femoral vein and left common femoral vein.
In addition to immediate anticoagulation, which of the following therapies would most likely prevent recurrence of pulmonary embolism in the subsequent week?
A. Cardiopulmonary bypass and surgical embolectomy
B. Tissue plasminogen activator
C. Catheter-guided direct removal of the emboli from the pulmonary arteries
D. Immediate insertion of an inferior vena cava filter
Answers and commentary
Correct answer: E. Unfractionated heparin or a low-molecular-weight heparin and continue anticoagulation postpartum.
Treatment for pulmonary embolism should not be delayed if there is a strong clinical suspicion of the diagnosis. Lower-extremity Doppler studies may or may not reveal the presence of a deep venous thrombosis. Pregnant women with a diagnosis of deep venous thromboembolism or pulmonary embolism are treated with either unfractionated heparin or a low-molecular-weight heparin during the pregnancy and for six weeks postpartum.
For pregnant women with risk factors, such as prior thromboembolism, antiphospholipid antibodies or prosthetic heart valves, adjusted-dose unfractionated heparin or low-molecular-weight heparin with low-dose aspirin therapy is recommended during pregnancy followed by long-term anticoagulation postpartum. Warfarin and thrombolytic therapy are relatively contraindicated during pregnancy. In addition, this patient is not a candidate for thrombolytic therapy because she is hemodynamically stable.
- Pregnant women with deep venous thromboembolism or pulmonary embolism are treated with either unfractionated heparin or a low-molecular-weight heparin during the pregnancy and for six weeks postpartum.
Correct answer: C. Determining the effect of bronchodilators on the patient's signs and symptoms.
The likelihood of pulmonary embolism after a negative CT scan is determined by the negative likelihood ratio of the scan as well as the pretest likelihood of pulmonary embolism. This patient with dyspnea has no specific symptoms, family history, or physical examination findings that suggest pulmonary embolism.
The patient has expiratory wheezing on examination and a history of asthma; therefore, resolution of the dyspnea and physical findings after administration of bronchodilators would provide strong evidence of an asthma exacerbation as the cause of his symptoms and thereby decrease the likelihood of his having pulmonary embolism.
The extent of the patient's recent ophthalmologic surgery may affect the risk/benefit relationship of anticoagulation. However, there is no evidence that a more extensive surgery (done under local anesthesia for a relatively brief time) would substantially influence the probability for pulmonary embolism. An elevated hemoglobin A1c may reflect recent episodes of hyperglycemia due to the patient's diabetes, but wouldn't indicate an elevated risk for venous thromboembolism.
The D-dimer fragment is shed into the blood when cross-linked fibrin, present within thrombi and within many areas of inflammation, is digested by fibrinolytic enzymes. D-dimer reflects the presence of thrombosis (or inflammation), but does not reflect the activity of thrombosis and would not decrease acutely in response to anticoagulation.
- D-dimer reflects the presence of thrombosis (or inflammation), but does not reflect the activity of thrombosis.
Correct answer: B. Enoxaparin.
Enoxaparin is cleared by the kidney. Although it does not usually require dose adjustment, this patient's chronic kidney disease would place the patient at high risk for accumulation of enoxaparin and subsequent overdose. If enoxaparin were to be used, it would require therapeutic drug monitoring and dosage adjustment.
Heparin is inactivated by plasma and endothelial proteins. The level of antithrombotic activity during heparin therapy would not be likely to increase because of renal impairment. Argatroban is cleared by the liver, and the presence of renal failure would not change its dosage or monitoring requirements.
Tissue plasminogen activator is generally given once as a continuous infusion over a short period of time (generally two hours) and has a half-life of about 30 minutes. Therefore, the infusion is not typically adjusted according to drug level monitoring. Furthermore, tissue plasminogen activator is cleared predominantly by the liver. Although there is some evidence to suggest that hepatic failure may cause an increase in its half-life, it is unclear that the effect would warrant a change in dosage. Warfarin is tightly bound by plasma proteins such as albumin and is metabolized by hepatic cytochrome P-450 isoenzymes, making its dosage requirements highly susceptible to many conditions and drug interactions. However, it is not significantly affected by renal impairment.
- Enoxaparin is cleared by the kidney, and if used in patients with chronic kidney disease, therapeutic drug monitoring would be required for possible dosage adjustment.
Correct answer: C. Continue warfarin and heparin until INR is therapeutic, and then discontinue heparin.
The INR in this patient is not yet therapeutic, and therefore, the warfarin dose needs to be adjusted and the patient requires ongoing anticoagulation that relies on continuation of heparin.
The patient's acute presentation following a prolonged air trip is not uncommon in this era of long-distance travel. The mechanism of effusion formation in pulmonary embolism involves both increased hydrostatic pressure in the pulmonary circulation and increased permeability in the visceral pleural vasculature. Approximately 80% of effusions associated with pulmonary emboli are therefore exudative. They are also usually small (less than one-third of the hemithorax) and unilateral and tend not to be progressive. The effusion in pulmonary embolism usually does not persist beyond 7 to 10 days after formation in the presence of underlying embolism.
The presence of a sanguineous or bloody effusion (erythrocyte count >100,000 cells/µL [100 × 109 cells/L]) associated with pulmonary embolism is not a contraindication to anticoagulant therapy. If a pleural effusion clearly increases in size during anticoagulant therapy, the development of hemothorax or an underlying infection should be excluded by thoracentesis. Insertion of an inferior vena cava filter should also be considered in such patients; however, in this patient anticoagulation should be maintained and placement of a vena cava filter is not indicated as the next management step in this case.
- Approximately 80% of effusions associated with pulmonary emboli are exudative, usually small and unilateral, and tend not to be progressive or to persist beyond seven days after formation.
Correct answer: B. Discharge on warfarin.
In most patients treated with heparin for pulmonary embolism, a substantial portion of their perfusion defects resolve within the first week, although complete resolution occurs in only a minority within this time. In this patient, only a relatively small portion of his defect has resolved, but it is still very early in treatment. Although he does have a 3% to 4% risk of developing chronic thromboembolic pulmonary hypertension, no intervention is required at this time beyond anticoagulation and follow-up.
There is no indication that anticoagulation was ineffective, and certainly no indication that low-molecular-weight heparin would be more effective. Pulmonary hypertension would be very unlikely to develop this early after an acute pulmonary embolism, so cardiac catheterization is not necessary. CT scanning to follow the resolution of pulmonary embolism is not well standardized and would add little to the work-up for this patient. Factor V Leiden mutation is not associated with slower resolution of pulmonary embolism and would not influence the treatment of this patient, whose embolism was provoked by a prolonged automobile ride.
- In most patients treated with heparin for pulmonary embolism, a substantial portion of their perfusion defects resolve within the first week.
- CT scanning to follow the resolution of pulmonary embolism is not well standardized.
Correct answer: D. Immediate insertion of an inferior vena cava filter.
All four options are reasonable approaches to prevent death resulting from hemodynamically significant pulmonary embolism, and none of them has been shown to be superior in randomized clinical trials. However, insertion of an inferior vena cava filter has been shown to reduce the short-term incidence of pulmonary embolism in patients who are receiving anticoagulation for deep venous thrombosis, and may, in this case, prevent a devastating recurrent embolization.
Cardiopulmonary bypass and surgical embolectomy will remove the proximally located pulmonary emboli, but will not prevent further embolization. These procedures must be performed by experienced surgical teams that can be rapidly mobilized. Even under these circumstances, embolectomy carries significant risks of morbidity and mortality. Thrombolytic therapy may decrease the size of the emboli and reduce right heart strain more rapidly than anticoagulation alone. However, there is no evidence that such therapy would protect the lungs from embolization of preexisting lower-extremity thrombi. Furthermore, thrombolytic therapy carries a significant risk of serious bleeding and may not, in the long run, resolve emboli more completely than would therapy with heparin alone. Catheter-guided direct emboli removal has been performed successfully in a few specialized centers, but it has not been widely adopted for treatment of pulmonary embolism. It would not decrease the risk of emboli from the left leg thromboses.
- Insertion of an inferior vena cava filter reduces the short-term incidence of pulmonary embolism in patients receiving anticoagulation for deep venous thrombosis.