Attending Version:
Pulmonary Embolus Module; created by Dr. David Garcia
Objectives for pulmonary embolism discussion:
1) Become familiar with diagnostic algorithms used to evaluate patients suspected of having
pulmonary embolism.
2) Develop an understanding of the various treatment modalities available to patients with
pulmonary embolism.
3) Review the risk factors and pathophysiology associated with pulmonary embolism.
4) Be able to estimate (using a clinical prediction rule) the pre-test likelihood of PE in a patient
presenting with symptoms of dyspnea or chest pain.
5) Be aware of the diagnostic clues for and the management of Heparin Induced
Thrombocytopenia (HIT)
References
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6.
7.
Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to
categorize patients probability of pulmonary embolism: increasing the models
utility with the SimpliRED D-dimer. Thromb Haemost 2000;83:416-20.
Aujesky D, Obrosky DS, Stone RA, et al. A prediction rule to identify low-risk
patients with pulmonary embolism. Arch Intern Med 2006;166:169-75.
Chagnon I, Bounameaux H, Aujesky D, et al. Comparison of two clinical prediction
rules and implicit assessment among patients with suspected pulmonary
embolism. Am J Med 2002;113:269-75.
Perrier A, Roy PM, Sanchez O, et al. Multidetector-row computed tomography in
suspected pulmonary embolism. N Engl J Med 2005;352:1760-8.
Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic
therapy for venous thromboembolic disease: the Seventh ACCP Conference on
Antithrombotic and Thrombolytic Therapy. Chest 2004;126:401S-428S.
Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Heparin plus alteplase
compared with heparin alone in patients with submassive pulmonary embolism. N
Engl J Med 2002;347:1143-50.
Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR.
Thrombophilia, clinical factors, and recurrent venous thrombotic events. Jama
2005;293:2352-61.
Case:
HPI: Pt is a 64 yo male with past medical history significant for hypertension and COPD, who presented
to ER with 2 weeks of LUQ abd pain and chest pain. Pain was sharp and constant, with radiation to back,
woke him from sleep, minimal relief with Pepto-Bismol. Some nausea, no vomiting or diarrhea, 10 lb wt
loss, + itching, orange-colored urine, and weakness, all going on for past week.
Admission work up indicated biliary obstruction, and CT scan of the abdomen revealed a mass in the
pancreatic head. Subsequent ERCP diagnosed adenocarcinoma. Pt. clinically improved after stent placed,
but on hospital day # 17 patient developed non-productive cough and pleuritic chest pain. Pt had been
ambulating in hallways, on sc heparin, and denied calf pain. A picc had been placed in LUE on HD # 14
due to lack of iv access.
Past Medical History:
Chronic Back Pain
Hypertension
Hypertriglyceridemia
Chronic Obstructive Pulmonary Disease
Fibromyalgia (ICD-9-CM 729.0)
Prostatitis (ICD-9-CM 601.9)
Urinary obstruction (ICD-9-CM 599.6)
Atypical Chest Pain (ICD-9-CM 786.59)
Family Medical History:
No family history of cancer, clots or DM.
Social History:
Served in the Air Force for ~25 years, as civil engineer and in Special Forces.
Smoked 1 1/2 packs x 20 years, quit about 15 years ago. Drank from age 16-26,
heavily on the weekends and while in Vietnam. Now has a beer or two a month.
No IVDU. Two amateur tattoos. Exposed to Agent Orange while in Vietnam.
Allergies: multiple BP meds, bactrim, statins, vicodin
Medications currently:
Tylenol
Irbesartan
Pantoprazole
Ciprofloxacin
Flagyl
Benadryl
Heparin 5000 units sc q 8 hours
PE on HD # 17:
Tm 98.9 bp 112/63 p 74 rr 20-28 02 sat 91-95% RA (all unchanged over last week)
Gen: alert, oriented, mild distress, facial flushing, skin without jaundice
Heent: Moist mucus membranes, no cervical adenopathy, no elevated JVP
Lungs: coarse upper airways sounds, but no crackles, normal excursion, and prolonged expiratory phase
bilaterally, no dullness to percussion, symmetric fremitus bilaterally.
CV: reg, s1s2, no mrg heard, strong peripheral pulses, normal carotid upstroke
Abd: normal bs, soft, mild tenderness to palpation RUQ, no obvious masses, liver at costal margin, spleen
not palpable.
Ext: L UE with picc line, no swelling, no edema. LE’s: negative homan’s sign, no erythema or tenderness,
no cords palpated.
Labs:
wbc/hgb/hct/plt: 11.2/13.6/39.8/339
Chem 7 wnl, creat 1.2
LFT's: T prot 6.0, Alb 2.8, Alk phos 154, AST 43, ALT 53, Tbili 1.2
Lipase 1175
Inr 1.0
What is the next step in management of this patient?
Patient has risk factors for DVT/PE due to underlying malignancy and prolonged hospitalization. In
addition, he has an indwelling catheter in his upper extremity, increasing risk of thrombosis of deep veins
in the upper extremity. The first step is CT scan of the thorax with PE protocol, or V/Q scan. A d-dimer
will likely be elevated due to underlying malignancy. In addition, it would be reasonable to start patient on
enoxaparin empirically while waiting for studies. Patient was diagnosed with PE, and ultrasound of his left
upper extremity revealed thrombosis in the deep veins.
Risk factors for pulmonary embolism
1. trauma, major surgery (especially orthopedic or tumor resection)
2. acute medical illness, especially if associated with immobilization
3. pregnancy, exogenous estrogen therapy
4. "hypercoagulable state", especially antiphospholipid syndrome
5. active malignancy
Pathophysiology of pulmonary embolism
1. typically caused by or associated with proximal deep vein thrombosis of the lower
extremities (can also be caused by proximal DVT of the upper extremities)
2. hypoxemia results from V/Q mismatch and/or "shunt" caused by a vasoconstrictor
response seen in the pulmonary vascular tree
3. shortness of breath and/or cough may result from irritation of J receptors
4. hypotension and reduction in cardiac output may result from sudden increase in
pulmonary artery pressures (hemodynamic collapse is more likely to occur in patients with
pre-existing heart or lung disease)
Diagnosis of pulmonary embolism
1. assess pretest probability [consider using a clinical prediction rule (1),(2,3)] - the absence
of an alternative diagnosis to explain the patient's symptoms is important
2. for outpatients with a low pretest probability of disease, a normal d-dimer result excludes
pulmonary embolism
3. D-dimer levels which are "abnormal" do not necessarily increase the probability of PE
4. for most patients whose pretest probability of disease is moderate or high, C. T.
angiography of the chest should be ordered first (exceptions: for patients allergic to
contrast by or at high risk of dye associated nephrotoxicity, a VQ scan may be preferable)
5. a negative CT scan excludes PE with adequate certainty in most patients (4) - if CT is
negative and clinical suspicion is very high, one may consider compression
ultrasonography of the legs as an adjunct test
Treatment of pulmonary embolism
1. for patients with normal renal function, low molecular weight heparin (LMWH) or a
pentasacchride (e.g. fondaparinux) are usually the treatments of choice (5)
2. note: because of insufficient evidence, outpatient therapy of acute pulmonary embolism
cannot be recommended
3. unfractionated heparin (UFH) with a target PTT 1.5-2.5 times control is an effective
therapy which may be preferable in some circumstances
a. Patient is being considered for thrombolytic therapy (see below)
b. Patient has a substantial risk for major bleeding (e.g. a postoperative patient) and the
short half-life and easy “reversibility” of UFH may be advantageous
4. Thrombolytic therapy should be strongly considered for patients who have hemodynamic
compromise and no obvious contraindications
5. Whether thrombolytic therapy should be used in patients without hemodynamic collapse
remains controversial (6)
6. Surgical embolectomy should be considered in cases of massive pulmonary embolism
with hemodynamic consequences where thrombolytic therapy is contraindicated
7. Inferior vena cava interruption is best reserved for patients in whom anticoagulation is
absolutely contraindicated (e.g. a patient who suffers pulmonary embolism within several
days of an operative procedure)
8. Any patient who experiences a new (or worsening) thrombosis (arterial or venous) while
receiving heparin or LMWH therapy should be evaluated for heparin induced
thrombocytopenia (HIT). Patients suspected of having HIT should have all heparin or
LMWH products discontinued immediately. The hematology service should be consulted
for alternate anticoagulation options.
Considerations for long-term therapy of PE (5)
1. In cases of idiopathic or unexplained PE, warfarin (target INR 2.0-3.0) should be
prescribed for a minimum of 6 months.
2. Anticoagulation for > 6 months should be considered in patients who
a. have had more than one DVT or PE
b. have a well documented “hypercoagulable state” (NB: the value of performing
hypercoagulability testing in all or most patients is questionable (7))
c. have significant pre-existing heart/lung disease (these patients are more likely to
suffer death or significant morbidity if they have recurrence after discontinuing
warfarin)
d. are ideal candidates for warfarin therapy (excellent adherence to monitoring, close
follow-up, few drug-drug interactions, low risk for bleeding)
3. In cases where the PE has been ‘provoked’ by a time-limited risk factor (e.g. pregnancy,
post-operative state, etc.), a shorter duration (e.g. 3 months) of warfarin therapy MAY be
acceptable
Questions
1. You are consulted about a 37 year-old woman who is on the trauma service.
Several days ago she was involved in an automobile accident that resulted in
multiple bone fractures and an emergent splenectomy. Four hours ago she
developed pleuritic chest pain and dyspnea. Computed tomography of the chest
demonstrates to filling defects in the main branches of the right pulmonary artery
and a similar defect in a subsegmental branch of the left pulmonary circulation. On
physical examination, the heart rate is 124 beats per minute, respiratory rate is 28
permanent and blood pressure is 89/60 mm Hg.
Which of the following is the most appropriate intervention at this time?
A. Tissue plasminogen activator
B. Low molecular weight heparin
C. Unfractionated heparin
D. Inferior vena cava filter
E. Echocardiography to look for right heart strain
Answer: the correct choice is "D". Although tissue plasminogen activator should be
considered in any patient who has hypotension in the setting of a pulmonary
embolism, this patient's recent major trauma and her recent invasive surgery preclude
her receiving either anticoagulation or thrombolytic therapy. This case (in which both
well documented pulmonary embolism and an absolute contraindication to
anticoagulant therapy are present) illustrates a rare situation in which most experts
would agree that IVC filter placement is indicated. Echocardiography would not
change the management of this patient.
2. A 27 year-old woman who underwent arthroscopic knee surgery one week ago
presents to the emergency department complaining of right-sided pleuritic chest
pain that began within the last 24 hours. She has a nonproductive cough but she
denies fever or chills. She has mild dyspnea that she attributes to her inability to
take a deep breath. She is taking ibuprofen for knee pain but she does not use any
other medications. Her past medical history is otherwise unremarkable. On
physical exam, the patient appears anxious but not acutely ill. Her heart rate is 86
BPM, the blood pressure is 116/84 mm Hg, her temperature is 38.1°. Pulmonary
exam demonstrates normal breath sounds in all fields but there is some splinting
on the right side. The incision over the right knee is healing well and there is no
swelling or pain in the lower extremities. The white blood cell count is 13,000.
Which of the following is the most appropriate at this time?
A.
B.
C.
D.
E.
transesophageal echocardiography
ventilation perfusion scan
helical computed tomography of the chest
compression ultrasonography of the lower extremities
quantitative D-dimer testing
Answer: the correct choice is "E". Pulmonary embolism must be considered in this
patient because she has dyspnea, pleuritic chest pain and a recent orthopedic
procedure. However, the "Wells prediction rule" (1) indicates that her pretest
likelihood of disease is low (her cough, low-grade fever and leukocytosis would make
infection at least as likely as pulmonary embolism). In patients like this, where the
pretest likelihood of disease is low, D-dimer testing should be performed first because
a normal D-dimer level excludes the possibility of pulmonary embolism with a high
degree of certainty. Helical computed tomography of the chest or a ventilation
perfusion scan of the lungs would be appropriate only if the D-dimer level is not low.
Echocardiography to document right heart strain may be appropriate for patients who
are too sick to undergo other more standard tests for pulmonary embolism but would
not be appropriate as a first test in this patient.