Ms. Smith is a 52-year-old woman 6 weeks status post knee replacement surgery presenting to the ED following two episodes of sharp chest pain lasting 5-10 minutes and accompanied by dyspnea.

Vitals
T 98.6°F

Temperature is within normal limits
P 113

Pulse is mildly increased
RR 21

Resiratory rate is mildly increased
BP 115/65

Blood pressure is within normal limits
O2 Sat 95%

Oxygen saturation is on the lower end of normal
BMI 26.3 kg/m 2
Her vital signs are reassuring. While her symptoms warrant urgent workup, she is hemodynamically stable and you should proceed with a history and physical exam.

Important clues:

Ms. Smith recently had knee replacement surgery, and, subsequently, immobility in her postoperative period. She endorses shortness of breath; sharp, left-sided pleuritic chest pain, unrelieved by rest; and acute-onset lower extremity swelling and pain.

Ms. Smith, a 52 year old woman, goes to the Emergency Department because she felt a sharp pain in her chest while she was at work. She has been working as a manager at a hair salon in the mall for the past 6 years. She was admitted about 6 weeks ago for a left knee replacement. She had to go back to work after the knee surgery sooner than expected. Today she has been having trouble moving around because she is easily fatigued. She was able to keep up despite the fatigue until about an hour into the job, when she suddenly started feeling sharp, 5/10 pain on the left side of her chest. She tried sitting and resting without much relief. The pain worsens when she takes a deep breath. Her discomfort was accompanied by shortness of breath, but she has had no sweating, nausea, or vomiting.

The first episode of chest pain occurred when she was cooking dinner yesterday. The pain lasted for approximately 5-10 minutes and disappeared. She sat down for a while and felt better so did not think much more about it. Since that episode of chest pain, this is the first time she has experienced similar pain. At no time has she attempted any specific measures to relieve her pain, other than rest. She becomes short of breath during these episodes, but describes no other
Shortness of breath triggered by physical activityexertional dyspnea
,
Shortness of breath that occurs while lying flat, and is relieved upon sitting up or standingorthopnea
, or
Sudden, severe shortness of breath that occurs during sleep and awakens the patient, and is usually relieved by sitting upnocturnal dyspnea
. Otherwise, she describes no other associated symptoms during these episodes of pain, including dizziness, nausea,
Excessive sweating (not due to physical exertion or temperature)diaphoresis
, or palpitations.

She thought the recovery from the knee surgery was going well. The swelling in her knee and leg had gotten much better, the pain was almost gone, and she has been working hard at physical therapy to increase her range of motion. However, since she’s had to start working again, she hasn’t been keeping up with PT as well. She also noticed the swelling getting worse.

This presentation is concerning for provoked acute deep vein thrombosis (DVT) causing a pulmonary embolism (PE). A provoked DVT is associated with a clear inciting risk factor (immobility following surgery in this case), whereas an unprovoked DVT occurs without any known precipitating factors. Other risk factors for provoked thrombosis include trauma, smoking, malignancy, and use of oral contraceptives. The clinical presentation can be scored using the Wells’ criteria* to give a pre-test probability for risk of DVT. A score of 3 or higher suggests that DVT is likely. In this case, Ms. Smith has a Wells’ score of 3 (+1 each for: major surgery within 12 weeks of presentation, left leg swelling, and left leg swelling of 3 cm greater than right).
* Please note that there is also a separate Wells’ criteria for PE, with different scoring.

Important clues:

Ms. Smith recently had knee replacement surgery, and, subsequently, immobility in her postoperative period. She endorses shortness of breath; sharp, left-sided pleuritic chest pain, unrelieved by rest; and acute-onset lower extremity swelling and pain.

Ms. Smith, a 52 year old woman, goes to the Emergency Department because she felt a sharp pain in her chest while she was at work. She has been working as a manager at a hair salon in the mall for the past 6 years. She was admitted about 6 weeks ago for a left knee replacement. She had to go back to work after the knee surgery sooner than expected. Today she has been having trouble moving around because she is easily fatigued. She was able to keep up despite the fatigue until about an hour into the job, when she suddenly started feeling sharp, 5/10 pain on the left side of her chest. She tried sitting and resting without much relief. The pain worsens when she takes a deep breath. Her discomfort was accompanied by shortness of breath, but she has had no sweating, nausea, or vomiting.

The first episode of chest pain occurred when she was cooking dinner yesterday. The pain lasted for approximately 5-10 minutes and disappeared. She sat down for a while and felt better so did not think much more about it. Since that episode of chest pain, this is the first time she has experienced similar pain. At no time has she attempted any specific measures to relieve her pain, other than rest. She becomes short of breath during these episodes, but describes no other
Shortness of breath triggered by physical activityexertional dyspnea
,
Shortness of breath that occurs while lying flat, and is relieved upon sitting up or standingorthopnea
, or
Sudden, severe shortness of breath that occurs during sleep and awakens the patient, and is usually relieved by sitting upnocturnal dyspnea
. Otherwise, she describes no other associated symptoms during these episodes of pain, including dizziness, nausea,
Excessive sweating (not due to physical exertion or temperature)diaphoresis
, or palpitations.

She thought the recovery from the knee surgery was going well. The swelling in her knee and leg had gotten much better, the pain was almost gone, and she has been working hard at physical therapy to increase her range of motion. However, since she’s had to start working again, she hasn’t been keeping up with PT as well. She also noticed the swelling getting worse.
This presentation is concerning for provoked acute deep vein thrombosis (DVT) causing a pulmonary embolism (PE). A provoked DVT is associated with a clear inciting risk factor (immobility following surgery in this case), whereas an unprovoked DVT occurs without any known precipitating factors. Other risk factors for provoked thrombosis include trauma, smoking, malignancy, and use of oral contraceptives. The clinical presentation can be scored using the Wells’ criteria* to give a pre-test probability for risk of DVT. A score of 3 or higher suggests that DVT is likely. In this case, Ms. Smith has a Wells’ score of 3 (+1 each for: major surgery within 12 weeks of presentation, left leg swelling, and left leg swelling of 3 cm greater than right).
* Please note that there is also a separate Wells’ criteria for PE, with different scoring.
MedicationDosage
Anticoagulant (low molecular weight heparin) used for prophylaxis and treatment of DVT. Also known as Lovenox (brand name).Enoxaparin
40 mg twice daily for 2 weeks after surgery (patient no longer taking)
Ibuprofen800 mg every 8 hours as needed for post-op pain (patient no longer taking as of 2 weeks ago)
Over-the-counter multivitaminDaily
Over-the-counter TumsAs needed for heartburn
Medical History None
Surgeries Left knee replacement six weeks ago.  She took her prescribed post-op DVT prophylaxis.

The patient was prescribed appropriate prophalaxis against venous thromboembolism. It is common practice to provide preventative therapy following Orthopedic surgery. While this reduces the risk of VTE it does not eliminate it.

Malignancy is a significant risk factor for thrombosis.
Hospitalizations Once for knee replacement surgery. Preoperative labs including BMP and CBC were normal.
Allergies No known drug allergies.
Screening Tests Normal colonoscopy at age 50, normal pap screen at age 52, and normal mammography at age 52.
Immunizations Up to date per patient.
Last Contact 2 months ago for pre-operative evaluation.
The HPI and ROS strongly suggest an initial diagnosis, but it’s important to review the rest of the history, as there is information found here that could change our diagnostic strategy.
Relation Notes
Father Passed away at 62 due to coronary artery disease.
Mother Currently 75 years old and healthy.
Grandmother 87 years old and had a hip surgery three years ago.
Siblings 49-year-old brother who is in good health.
Children Two adult children. Both healthy. Both deliveries were vaginal and normal.  No spontaneous abortions.

A personal or family history of recurrent spontaneous abortions can be concerning for a clotting disorder. This could trigger additional workup.
Other Blood Relatives None. No family history of sudden death, clotting disorders, or spontaneous abortions.
Occupation Manager at hair salon in the mall for the past six years. Currently covering two salons because the other manager quit, so she has been working extra. This has caused some stress because of the extra hours, rare days off, and extra managerial duties. She has also had to train many new employees since so many seem to be leaving.
Education High school grad.
Alcohol She has an occasional drink, usually when socializing on the weekends.
Smoking Prior smoker, 10
Unit for measuring amount a person has smoked over a long period of time. Calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the patient has smoked.pack years
. She quit when she had her first child.
Smoking has a small positive association with risk of thrombosis, though this is less concerning in Ms. Smith’s case, as she quit many years ago.
Drugs Denies any illicit drug use.
Caffine 1 cup of coffee per day.
Diet Unchanged. 3 meals a day.
Exercise Gardening about once a week.
Hobbies Gardening, reading, and spending time with close family and friends.
Stress Stress from her job, but it is not overwhelming. No other major life changes
Travel Nothing out of the country.
Sexual Monogamous with her husband of 30 years.
GEN Well-nourished female appearing stated age.
HEENT Normal. Moist mucus membranes, sclera clear, good dentition.
Neck Normal. Carotid pulses symmetric, no bruits auscultated. No jugular venous distention. No 
Palpable enlargement of one or more lymph nodeslymphadenopathy
.
Chest Clear to auscultation bilaterally. Mild dyspnea.
Cardio Normal S1 and S2. Mild tachycardia. No murmurs, rubs, or gallops. Point of maximal impulse not displaced.
Abdomen Soft, non-tender, non-distended. No 
Abnormal enlargement of one or more organsorganomegaly
.
Extremities Left leg with 2+ 
Swelling in the skin that holds a dimple after being pressed for several seconds; occurs due to excess fluid buildup in the body, and most often affects the legs, ankles, or feetpitting edema
. Left leg diameter 3 cm larger than right leg. Lower left leg 
Abnormal redness of the skin or mucous membraneserythematous
 and warm. TKR incision site is not tender or 
Abnormal redness of the skin or mucous membraneserythematous
. Varicose veins present on left. Right leg with 1+ 
Swelling in the skin that holds a dimple after being pressed for several seconds; occurs due to excess fluid buildup in the body, and most often affects the legs, ankles, or feetpitting edema
 but no erythema or tenderness.

The physical exam is strongly suggestive of a DVT in the left lower extremity. The key finding here is unilateral calf swelling and pitting edema. While not described here, the Homan’s sign test is a classic test for DVT, and is positive if the patient experiences calf pain with passive dorsiflexion of the ankle. However, this test has low sensitivity and specificity, and cannot be used alone to make a diagnosis.

Neurologic Alert and oriented x4, cranial nerves 2-12 grossly intact, normal finger to nose, normal tandem gait, normal strength throughout, normal speech. Sensory intact to light touch in bilateral lower extremities.
What else could be on your differential?
The presentation of a pulmonary embolism (PE) can be quite variable, and as such the differential can be extensive. Based on Ms. Smith’s chest pain and shortness of breath, the etiology is likely cardiovascular or pulmonary. Other than PE, other key diagnoses to consider include:
  • Acute coronary syndrome
  • Cardiac arrhythmia
  • Acute pericarditis
  • Heart failure
  • Pneumonia
  • Pneumothorax
  • Pleural effusion
  • Asthma or bronchospasm

Value Calculator

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Lab Patient Value Normal Range
BMP: Calcium 8.9 mg/dL 8.6 to 10.3 mg/dL
Complete Blood Count (CBC) WBC: 8.7
Hemoglobin: 14.1
Hematocrit: 42.5
Platelets: 298 		4.5-11
12.3-15.3 (Women)
35.9-44.6 (Women)
150-450
CBC Differential Neutrophils: 66%
Lymphocytes: 28%
Monocytes: 3%
Eosinophils: 2%
Basophils: 1% 		40%-60%
20%-40%
2%-8%
1%-4%
0.5%-1%
Comprehensive Metabolic Panel (CMP) Alkaline Phosphatase: 88 U/L
AST: 22 U/L
ALT: 38 U/L
Total bilirubin: 0.4 mg/dL
Albumin: 3.8 g/dL
Total protein: 7.7 g/dl/L 		20-130 U/L
8-33 U/L
4-36 U/L
0.1-1.2 mg/dL
3.4-5.4 g/dL
6.0-8.3 g/dl/L

A CMP will give you the same information as a BMP, but also includes liver function tests. This may be useful if there is concern for liver pathology, but in this case the BMP is adequate (and less expensive).

A type and screen is used to determine a patient’s ABO blood group, Rh type, and screens for non-ABO antibodies that may be present against donor red blood cells. It would be important to order this test if there was an anticipated need for a blood transfusion, but this patient’s hemoglobin concentration is adequate (rule of thumb is to consider transfusing when less than 7 g/dL), and does not have any identified bleeding risks. Read more about Choosing Wisely guidelines regarding transfusions here.

These are all tests that could be ordered as part of a thrombophilia workup. Several of these tests (ex: protein C, protein S, and ATIII activity) are inherently abnormal in the setting of an acute clot, so their diagnostic utility is limited in this setting. There is evidence [link] that testing for inherited thrombophilia does not reduce recurrence of DVTs and PEs. For Ms. Smith in particular, who does not have a history of recurrent thromboses and a clear inciting risk factor for her DVT, ordering extensive thrombophilia testing is a poor use of resources. Even when a diagnostic investigation for thrombophilia is indicated, it is best pursued at the completion of the initial therapy, when the patient is recovered and off anticoagulation.
Test used to determine the patient’s blood group (ABO) and Rh typeBlood type and screen
O+ (antibody negative) N/A
Prothrombin time test (PT) measures the speed of blood clotting by means of the extrinsic and common pathways of the coagulation cascade; international normalized ratio (INR) is a standardized conversion of the PT by comparing it to a reference valuePT/INR
14 sec/1.0 (normal) n/a
Partial thromboplastin time measures the speed of blood clotting by means of the intrinsic and common pathways of the coagulation cascadePTT
25 sec (normal) n/a
Test that detects poor anticoagulant response to activated protein C (APC), which may increase the risk of thrombosisAPC resistance screen
Negative N/A
Genetic test used to evaluate for a variant of human factor V, one of the most common hereditary hypercoagulability disordersFactor V Leiden
Normal N/A
Test used to measure the activity of the factor V protein, which serves an important role in the regulation of blood coagulationFactor V Activity
152% (normal) N/A
Tests for the presence of a group of prothrombotic immunoglobulins directed against phospholipid-binding proteinsAntiphospholipid antibody panel
Normal N/A
Russell viper venom time tests for the presence of lupus anticoagulant, a prothrombotic antibody that binds to phospholipids and cell membrane proteinsRVVT
34 sec (normal) N/A
Genetic test used to evaluate for a mutation that causes higher levels of the clotting factor prothrombin (factor II), which may increase the risk of thrombosisPT G20210A mutation
Negative N/A
Test used to measure the activity of protein C, a natural anticoagulant that is activated to APCProtein C activity
102% (normal) N/A
Test used to measure the quantity of protein S, a natural anticoagulant that acts as a cofactor for APCProtein S level
45 IU/dL (normal) 27-61 IU/dL
Test used to measure the activity of antithrombin III, a natural anticoagulant that inactivates several clotting factors in the coagulation cascadeATIII activity
92% (normal) N/A
Genetic test used to evaluate for a mutation in methylenetetrahydrofolate reductase, which may result in the development of homocysteinuria, a disorder in which the body is unable to metabolize methionine. Symptoms include lens dislocation, myopia, osteoporosis, and abnormal blood clotting.MTHFR mutation
Normal N/A
Test used to measure the activity of homocysteine; elevated levels may increase the risk of thrombosisHomocysteine level
18 mm/L (normal) N/A
Test used to measure levels of d-dimer, a degradation product of fibrin; elevated levels serve as a marker of activation of coagulation and fibrinolysisD-dimer
6.45 mg/L (high) N/A

D-dimer is an acute-phase reactant, meaning that it is elevated in response to many sources of inflammatory stimuli, including infection, trauma (including surgery), autoimmune disorders, and malignancy. As such, an elevated D-dimer alone is insufficient to make a diagnosis of PE. A normal D-dimer can be used to rule out PE in patients with a low or intermediate probability of PE. For Ms. Smith, who has a clinical presentation highly consistent with PE, a D-dimer would not be useful. A negative result would not be sufficient to rule out the diagnosis of PE.

A fibrinogen test is unlikely to be helpful for diagnosis of PE, as fibrinogen levels could be variable based on a number of factors. Fibrinogen, like D-dimer, is an acute-phase reactant. However, fibrinogen could also be lowered postoperatively as a result of appropriate clot formation during surgical healing.
Test used to measure levels of fibrinogen, a glycoprotein that is converted to fibrin to form a blood clotFibrinogen
322 mg/dL N/A
Image Result
EKG Sinus tachycardia

An EKG is essential for ruling out other dangerous conditions—such as ACS—that may resemble the presentation of PE, though it will not confirm a diagnosis of PE. The most common EKG finding in the setting of PE is sinus tachycardia.

A chest X-ray will be unremarkable in the setting of a PE, but is important for ruling out other conditions—such as pneumonia or pneumothorax—that may present similarly to PE.

A CT pulmonary angiogram is the diagnostic modality of choice when PE is suspected. It would not be appropriate if the clinical suspicion for PE was low, as it would expose the patient to unnecessary radiation.

A V/Q scan is appropriate for diagnosing PE in patients with a contraindication to CT angiogram, such as a severe contrast allergy or high risk of contrast nephropathy. In the absence of a contraindication, however, a CTA is usually preferred for diagnosis (as it is significantly faster to perform and has a higher diagnostic accuracy).

A lower extremity ultrasound is the standard imaging test for diagnosing DVT. While outside the scope of this case, there are different approaches for ordering a CT angiogram vs. a lower extremity ultrasound to diagnose DVT and PE. Just remember that you could make a case for ordering either test, but you generally would not order both.

A knee X-ray would have been appropriate if there were concerns specifically relating to the implant (ex: loosening, misalignment). However, it is not useful in the diagnosis of DVT, and represents a poor use of resources. Additionally, ordering unnecessary testing can lead to delay in making a proper diagnosis.
Chest X-ray Normal
CT pulmonary angiogram Pulmonary embolus in right main pulmonary artery
Ventilation-perfusion scan is a nuclear medicine test that uses radioactive material to examine airflow and blood flow in the lungsV/Q scan
High probability V/Q scan by PIOPED criteria
Lower extremity ultrasound Non-occlusive thrombus in distal femoral vein
Knee X-ray 3 views Left knee prosthesis in appropriate position, no fracture, normal soft tissue
How did you do?
You spent a total of $.
Those that are absolutely indicated to manage and treat the clinical scenario:
    Labs
  • BMP
  • PT
  • PTT
  • CBC
    Imaging
  • EKG
  • Chest X-ray
  • Lower extremity ultrasound
  • CT pulmonary angiogram
Those that are not indicated and would not change management but have minimal harm to patient:
    Labs
  • Type and screen
  • CMP
  • D-dimer
    Imaging
  • Knee X-ray
Those that should not be done and may harm the patient:
    Labs
  • APC resistance screen
  • Factor V Leiden
  • Factor V activity
  • Antiphospholipid antibody panel
  • RVVT
  • PT G20210A mutation
  • Protein C activity
  • Protein S level
  • ATIII activity
  • MTHFR mutation
  • Homocysteine level
  • Fibrinogen
    Imaging
  • V/Q Scan
By comparison, we’ve determined that by following evidence-based best practices, the cost to ensure proper management for Ms. Smith’s presentation is approximately $440.
Takeaways
Venous thromboembolism (VTE)—representing a spectrum of disease from DVT to PE— is a common and potentially dangerous condition that leads to significant morbidity, mortality, and expenditure within our health care system. One study estimates that there are 900,000 cases of PE and DVT per year. In 2012, Medicare paid $6,000 per hospitalization, for a total of almost $250 million dollars. It is important to accurately diagnose and treat this condition while minimizing health care expenditure.

Remember that high-value care means practicing in a manner that is patient-centered and evidence-based, while refraining from using resources in way that is likely to be wasteful or harmful. Of course, we recognize that in a real-world clinical setting, patient presentations and questions around resource utilization are not nearly as clean-cut as displayed here. Patient preferences, goals of care, and unique circumstances must all be accounted for. As such, the goal should not be to exactly match the minimum cost that we’ve provided for each case, but instead to use these cases as an exercise to develop a pattern of thinking about why or why not you would order a given test, procedure, or medication, and what value it is likely to add to your care plan.
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