A 58-year-old woman complains of the sudden onset of right chest pain and shortness of breath 6 days following an uncomplicated left hemicolectomy for adenocarcinoma of the descending colon. The patient has had an uncomplicated postoperative course until this time. During your evaluation, she appears anxious and is unable to remain comfortable. Her temperature is 37.9°C (100.2°F), pulse rate 105 beats/min, blood pressure 138/80 mm Hg, and respiratory rate 32 breaths/min. She is receiving O2 by nasal canula with an O2 saturation of 96% by pulse oximetry. Despite this oxygen saturation, the patient continues to complain of difficulty breathing. There is no jugular venous distension. Her lungs are clear, with diminished breath sounds in both bases. Her cardiac examination reveals sinus tachycardia. Her abdomen is slightly tender and without distension, and the surgical incision is normal in appearance. Her legs reveal mild edema bilaterally and tenderness in the left calf. Laboratory evaluations reveal a white blood cell (WBC) count of 11,000/mm3 with a normal differential, normal hemoglobin and hematocrit values, and a normal platelet count. The electrolyte levels are likewise normal. An arterial blood gas study reveals pH 7.45, Po2 73 mm Hg, Pco2 34 mm Hg, and HCO3 24 mEq/L. A 12-lead electrocardiogram (ECG) reveals sinus tachycardia. The creatine kinase and troponin levels are within normal limits. A portable chest radiograph (CXR) demonstrates no infiltrates or effusions and minimal atelectasis in both lower lung fields.
What is the most likely diagnosis?
What should be your next step?
ANSWERS TO CASE 18: Venous Thromboembolic Disease
Summary: A 58-year-old woman has acute chest pain and dyspnea postoperatively. The results from cardiopulmonary and abdominal examinations are nonspecific. She has a minimally elevated leukocyte count and normal cardiac enzyme levels. Arterial blood gas studies indicate respiratory alkalosis and hypoxemia. The CXR and ECG show no obvious pathology.
• Most likely diagnosis: Pulmonary embolism (PE) is very likely with the sudden onset of chest pain and shortness of breath in a patient without pulmonary or cardiac pathology.
• Next step: Empirical systemic anticoagulation with confirmatory imaging pending.
1. Know the risk factors and causes of venous thromboembolic disease.
2. Know the applications and effectiveness of prophylactic measures for deep vein thrombosis (DVT).
3. Learn the diagnostic and therapeutic approaches for patients with suspected venous thromboembolism.
The differential diagnosis for a 58-year-old woman with the sudden onset of chest pain and shortness of breath during the postoperative period includes cardiac ischemia, respiratory tract infection, acute lung injury, and PE. In this case, PE should be strongly considered based on the history of acute dyspnea and chest pain with a normal WBC count, normal ECG and CXR results, and normal cardiac enzyme levels. As for most patients, making a definitive diagnosis of PE based on clinical criteria is difficult. However, this evaluation is vital in determining the level of clinical suspicion (pretest probability), which influences the diagnostic precision of subsequent imaging studies. In this case, the clinical picture indicates a high clinical probability of PE. The decision to initiate systemic anticoagulation without a confirmed diagnosis of PE is justifiable based on a high clinical suspicion and the absence of contraindications to anticoagulation. As one decides whether to initiate empirical treatment, it is important to bear in mind that patients treated with early aggressive anticoagulation therapy are less likely to experience treatment failure or develop recurrences.
APPROACH TO: Deep Venous Thrombosis and Pulmonary Embolism
VENOUS DUPLEX IMAGING: An accurate, noninvasive imaging modality combining ultrasonography and Doppler technology to assess the patency of veins and the presence of blood clot in veins; it is especially useful for the lower extremities.
VENTILATION/PERFUSION (V/Q) SCAN: A radioisotope scan used to identify V/Q mismatches, which can indicate PE and other pulmonary conditions. Results must be interpreted based on coexisting pulmonary pathology and the clinical picture. This study is less commonly performed, as CT angiography has become more commonly available and improved in diagnostic sensitivity.
COMPUTED TOMOGRAPHY: A vascular contrast study involving CT imaging with a sensitivity for PE detection ranging widely from 64% to 93%; it is highly sensitive for PE involving the central pulmonary arteries but insensitive for subsegmental clots. Some advocate that it not be used as the initial imaging study and that it is perhaps best used with venous duplex or pelvic CT venography for better accuracy.
PULMONARY ANGIOGRAPHY: Considered the gold standard for the diagnosis of PE. It is accurate (approximately 96%), carries a false-negative rate of 0.6%, and especially has greater sensitivity than CT for subsegmental and chronic PE. The significant drawbacks are a major procedural complication rate of 1.3%, mortality rate of 0.5%, and the time delay associated with the procedure.
THROMBOLYTIC THERAPY: Thrombolysis for PE has survival advantages in patients with massive PE, especially when it is associated with right heart dysfunction. Tissue plasminogen activator (TPA) is the most commonly used agent and may be given systemically or by catheter-directed infusion into the clot. Recent major surgery (such as within a 10-day period) and recent severe closed head injury are contraindications to systemic thrombolytic therapy.
PULMONARY ARTERY CATHETER EMBOLECTOMY: Surgical retrieval of clots in the pulmonary artery through a median sternotomy, requiring cardiopulmonary bypass. Major indication: massive PE with hemodynamic instability and hypoxia, where thrombolytic therapy is contraindicated. It is associated with 30% to 60% mortality.
The development of acute thromboembolic complications is presumed to be related to stasis, hypercoagulability, and vein wall injury that occur as the result of local and systemic effects of trauma and operative injuries, aging, and preexisting medical conditions. The incidence of DVT in general surgery patients without thromboprophylaxis is estimated at approximately 15% to 30%, with most being asymptomatic.
Major orthopedic surgery and major trauma are associated with a significantly greater risk of this complication. Most patients with DVT have involvement of the tibial-level veins and may remain asymptomatic; however, involvement of the femoral and/or iliac veins dramatically increases the risk of PE and symptoms, such that approximately 30% to 50% of these patients may develop PE. All patients with identifiable risk factors should undergo prophylaxis against DVT/PE, which is effective in reducing the complication rate. In high-risk patients, prophylaxis is effective in reducing the occurrence of DVT/PE (Table 18–1).
Table 18–1 • APPROXIMATE DEEP VENOUS THROMBOSIS PREVALENCE WITH AND WITHOUT PROPHYLAXIS
A suggested diagnostic approach is shown in Figure 18–1.
Figure 18–1. Diagnostic and treatment strategy for patients with suspected DVT/PE.
In general, all patients with documented DVT and PE should undergo treatment with systemic anticoagulation therapy with heparin infusion, oral warfarin, or subcutaneous low-molecular-weight (LMW) heparin. The duration of therapy for uncomplicated DVT is generally 3 months. Patients with PE and no identifiable hypercoagulability state should be treated for 6 months, and patients with documented hypercoagulability should be considered for lifelong therapy (Table 18–2). Recurrent PE despite adequate anticoagulation, complications from anticoagulation, and contraindication to anticoagulation are the three major indications for vena cava filter placement.
Table 18–2 • DEEP VEIN THROMBOSIS TREATMENT AND EFFICACY
18.1 A 45-year-old man with diabetes, who underwent laparoscopic colectomy 4 days ago, complains of pain and swelling in the right calf and thigh of 2 days’ duration. Which of the following is the next appropriate step in the treatment of this patient?
A. Begin systemic thrombolytic therapy.
B. Perform CT angiography of the chest and pelvis.
C. Perform CT pulmonary angiography.
D. Determine the D-dimer level. Perform pulmonary angiography if this level is elevated.
E. Perform a lower extremity venous duplex scan.
18.2 In which of the following patients with confirmed femoral venous thromboses is unfractionated heparin therapy contraindicated?
A. A hemodynamically stable 80-year-old man with a documented PE
B. A 20-year-old man who sustained a closed head injury 6 days ago
C. A 23-year-old woman in her third trimester of pregnancy
D. A 44-year-old woman with heparin-induced thrombocytopenia
E. A 23-year-old man with liver injury sustained from a gunshot wound 5 days ago, who now develops femoral DVT
18.3 A 35-year-old man with right femur fracture complains of dyspnea and left leg pain. He undergoes a V/Q scan, interpreted as being of low probability for PE. Which of the following is the most accurate statement?
A. The probability of PE is less than 1%.
B. The probability of PE is as high as 40%.
C. The next test should be a determination of the serum D-dimer level.
D. Pulmonary angiography should be performed to rule out DVT definitively.
E. Empiric therapy for PE with systemic heparinization is not indicated.
18.4 Which of these is the most appropriate DVT prophylactic measure for a 36-year-old man who just underwent an exploratory laparotomy, distal pancreatectomy, splenectomy, and gastric repair for a gunshot wound to the abdomen? The patient had approximately 3000 mL of blood loss prior to surgical control of his bleeding and repairs of his injuries. Following his operation, he has been stable in the ICU with a hematocrit of 28% and international normalized ratio (INR) of 1.7.
A. LMW heparin.
B. 5000 U of fractionated heparin TID.
C. 5000 U of fractionated heparin BID.
D. Pneumatic compression devices.
E. Withhold DVT prophylaxis until the INR returns to normal.
18.1 D. Obtain a venous duplex scan of the legs. Systemic thrombolytic therapy is indicated only if patients have proven proximal DVT. D-dimer levels are elevated in 99.5% of all patients with DVT/PE, but this is also seen following trauma and surgery, and so the test is highly sensitive but nonspecific. In this postoperative patient, D-dimer levels would be elevated and not specific for DVT. CT angiography of the chest and pelvis is highly sensitive in diagnosis of pulmonary embolism, but PE is not the clinical concern in this patient.
18.2 D. Heparin-induced thrombocytopenia, which is usually an immunoglobin G–mediated reaction, is a contraindication to heparin therapy. Heparin does not cross the placenta and is not contraindicated during pregnancy. Although the timing of heparin therapy or heparin thromboembolism prevention in postinjury or postoperative patients has not been evaluated by randomized prospective trials, most centers would give head injury patients LMW heparin for DVT prophylaxis 48 hours after the injury. Similarly, DVT prophylaxis with LMW heparin could be initiated within 24 hours after intra-abdominal injuries.
18.3 B. The probability of PE can be as high as 40% in a patient with a low-probability V/Q scan. The probability of PE in a patient with a low-probability V/Q scan and low clinical suspicion is approximately 4%. If the patient’s V/Q scan indicates a low probability and the clinical suspicion is intermediate or uncertain, the risk for PE is approximately 16%. A venous duplex scan or CT angiography is indicated for further evaluation of intermediate- and high-risk patients. It is acceptable to initiate empiric treatment for PE based on clinical assessment while diagnostic studies are pending, as long as the risk of complications associated with empirical treatment does not outweigh the risk associated with delayed management.
18.4. A. LMW heparin is more effective than fractionated heparin in the prevention of DVT in high-risk individuals. Trauma patients with a history of significant blood loss are considered extremely high-risk patients. In the majority of cases, thromboprophylaxis can be initiated within 36 hours of the injury. Pneumatic compression devices have no proven efficacy in the prevention of DVT in the high-risk trauma population. Elevation of the INR in the post-traumatic setting generally indicates coagulopathy induced by massive injury, and this does not appear to have a protective effect for patients in terms of thromboembolism development.
Up to 95% of patients with venous thromboembolic complications have recognizable risk factors and therefore would benefit from prophylactic measures.
The benefits of prophylactic measures against DVT/PE are additive and should be applied together to reduce risk maximally in very-high-risk patients.
A serial surveillance duplex scan should be considered in very-high-risk patients despite prophylactic measures.
Heparin-induced thrombocytopenia is a contraindication to heparin therapy.
The main indication for pulmonary embolectomy is massive PE with hemodynamic instability or refractory hypoxemia.
Upper extremity DVT (such as subclavian vein thrombosis) carries a much higher PE risk than lower extremity DVT.
Retrievable inferior vena cava (IVC) filters are indicated for patients who develop DVT/PE in the face of appropriate prophylaxis. Filters are also indicated for patients with known thromboembolism and contraindication or complications associated with anticoagulation.
Geerts WH, Bergquist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:381S-453S.
Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:454S-545S.
Liem TK, Moneta GL. Venous and lymphatic disease. In: Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 9th ed. New York, NY: McGraw-Hill; 2010:777-801.