Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism JASON WILBUR, MD, and BRIAN SHIAN, MD, Carver College of Medicine, University of Iowa, Iowa City, Iowa Venous thromboembolism manifests as deep venous thrombosis (DVT) or pulmonary embolism, and has a mortal- ity rate of 6 to 12 percent. Well-validated clinical prediction rules are available to determine the pretest probability of DVT and pulmonary embolism. When the likelihood of DVT is low, a negative D-dimer assay result excludes DVT. Likewise, a low pretest probability with a negative D-dimer assay result excludes the diagnosis of pulmonary embo- lism. If the likelihood of DVT is intermediate to high, compression ultrasonography should be performed. Imped- ance plethysmography, contrast venography, and magnetic resonance venography are available to assess for DVT, but are not widely used. Pulmonary embolism is usually a consequence of DVT and is associated with greater mortality. Multidetector computed tomography angiography is the diagnostic test of choice when the technology is available and appropriate for the patient. It is warranted in patients who may have a pulmonary embolism and a positive D-dimer assay result, or in patients who have a high pre- test probability of pulmonary embolism, regardless of D-dimer assay result. Ventilation-perfusion scanning is an acceptable alternative to computed tomography angiography in select settings. Pulmonary angiography is needed only when the clinical suspicion for pulmo- nary embolism remains high, even when less invasive study results are negative. In unstable emergent cases highly suspicious for pulmo- nary embolism, echocardiography may be used to evaluate for right ventricular dysfunction, which is indicative of but not diagnostic for pulmonary embolism. (Am Fam Physician. 2012;86(10):913-919. Copyright © 2012 American Academy of Family Physicians.) ILLUSTRATION TODD BY BUCK ▲ Patient information: enous thromboembolism (VTE) have an associated pulmonary embolism by A handout on this topic is is a blood clotting condition that lung scan; about 70 percent of patients pre- available at http://family doctor.org/familydoctor/ has two major manifestations: deep senting with pulmonary embolism are found 2,3 en/diseases-conditions/ venous thrombosis (DVT) and pulmo- to have DVT in the legs. deep-vein-thrombosis. Vnary embolism. In the general U.S. popula- To provide prompt and accurate diagnosis, html. tion, the incidence of first-time VTE is about clinical prediction rules and diagnostic algo- 100 per 100,000 person-years and increases rithms have been developed for VTE. The with advancing age. About one-third of American Academy of Family Physicians patients who have symptomatic VTE present and the American College of Physicians with pulmonary embolism, and two-thirds developed a joint guideline on the diagnosis present with DVT.1 Within one month of and management of VTE,4 and the European diagnosis, the mortality rate is approximately Society of Cardiology has developed diag- 6 percent in patients with DVT and 12 percent nosis and management guidelines for acute in patients with pulmonary embolism.1 pulmonary embolism.5 A common approach Compared with DVT, pulmonary embo- is to use a validated prediction rule for risk lism is more often fatal, has a higher recur- stratification, screen with D-dimer assay as rence rate, and presents with less specific appropriate, and if necessary, perform the symptoms. Pulmonary embolism is usually appropriate imaging studies to confirm or a consequence of DVT. About 40 percent of exclude VTE. This article reviews the diag- patients with proximal DVT are found to nosis of pulmonary embolism and DVT. Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2012 American Academy of Family Physicians. For the private, noncommer- Novembercial 15, use 2012of one ◆individual Volume user 86, of Number the Web site.10 All other rights reserved.www.aafp.org/afp Contact [email protected] for copyright questionsAmerican and/or permission Family Physician requests. 913 DVT and Pulmonary Embolism SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References In patients with a low pretest probability of DVT or pulmonary embolism, a negative result from a high- C 7, 10 sensitivity D-dimer assay is sufficient to exclude venous thromboembolism. Validated clinical prediction rules can be used to estimate pretest probability of DVT and pulmonary C 16, 17, 20 embolism, and guide further evaluation. Compression ultrasonography should be the initial test for patients with intermediate to high pretest C 23, 26 probability of DVT in the lower extremities. In patients with intermediate to high pretest probability of DVT, negative ultrasonography alone is C 21, 23, 24 insufficient to exclude the diagnosis of DVT. Further assessment is recommended, including checking the D-dimer level and repeating ultrasonography in one week if the D-dimer level is elevated. For patients with contraindications to computed tomography, including contrast allergy, renal disease, and C 34, 35 pregnancy, ventilation-perfusion scanning is the preferred imaging modality for evaluation of possible pulmonary embolism. DVT = deep venous thrombosis. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp. org/afpsort.xml. Risk Factors The pathogenesis of VTE is often described by Vir- Table 1. Risk Factors for Venous chow’s triad, which proposes that venous thrombosis is Thromboembolism the result of at least one of three etiologic factors: hyper- coagulability, alterations in blood flow, and endothe- Strong risk factors (odds ratio > 10) lial injury or dysfunction.6 Risk factors for VTE reflect Fracture (hip or leg) these underlying pathophysiologic mechanisms, and Hip or knee replacement between 75 and 96 percent of patients with VTE have Major general surgery at least one risk factor.6 If VTE is suspected, risk factors Major trauma should be assessed to determine the pretest probability. Spinal cord injury Some factors suggest greater risk of VTE than others Intermediate risk factors (odds ratio 2 to 9) (Table 1).6 Arthroscopic knee surgery Central venous lines D-dimer Chemotherapy D-dimer is a fibrin degradation product, a small protein Chronic heart or respiratory failure fragment detectable in the blood after a blood clot is Hormone therapy degraded by fibrinolysis. D-dimer assays are fast, accu- Malignancy rate, and readily available. However, D-dimer assays Oral contraceptive therapy vary in their sensitivity and specificity. Enzyme-linked Paralytic stroke immunosorbent assay (ELISA), quantitative rapid Pregnancy/postpartum Previous venous thromboembolism ELISA, and advanced turbidimetric D-dimer determina- tions are more than 95 percent sensitive for VTE.7 Thrombophilia The negative predictive value of the high-sensitivity Weak risk factors (odds ratio < 2) D-dimer assay is about 94 percent.7,8 However, the Bed rest longer than three days D-dimer assay is useful only for ruling out VTE if results Immobility due to sitting (e.g., car or air travel longer than eight are negative; positive results are not diagnostic because hours) many conditions, such as impaired renal function, Increasing age ongoing blood loss, pregnancy, and atrial fibrillation, Laparoscopic surgery Obesity (body mass index greater than 40 kg per m2) can cause D-dimer levels to rise. A negative D-dimer Pregnancy/antepartum assay result combined with a low pretest probability Varicose veins determined by a well-validated clinical prediction rule suffices to rule out VTE; no further workup is neces- Adapted with permission from Anderson FA Jr, Spencer FA. Risk factors sary in such cases, even in patients who have had a prior for venous thromboembolism. Circulation. 2003;107(23 suppl 1):I10. VTE.4,9-11 In patients with intermediate to high pretest 914 American Family Physician www.aafp.org/afp Volume 86, Number 10 ◆ November 15, 2012 DVT and Pulmonary Embolism probability of VTE, a D-dimer assay should not be per- best known. It divides patients into low-, intermediate-, formed initially because a negative result cannot safely and high-risk categories14-16 (Table 216). The preva- exclude the diagnosis of VTE. lence of DVT is 5, 17, and 53 percent for these groups, respectively.17 Clinical Presentation Similarly, in cases of suspected pulmonary embolism, The classic clinical presentation of DVT includes swell- a pretest probability should be assigned. Implicit clinical ing, pain, warmth, and redness in the involved extrem- judgment, essentially the physician’s estimation of the ity. Alternatively, DVT can occur asymptomatically. probability of pulmonary embolism in a given patient, Individual symptoms are neither sensitive nor specific has been evaluated and found to be fairly accurate for for DVT. Trauma, infection, peripheral artery disease, classifying patients into three categories of clinical like- and other venous diseases can present with clinical fea- lihood of pulmonary embolism: low, intermediate, and tures similar to DVT. Furthermore, DVT can coexist high.5 Because this approach lacks standardization and with any of these processes. is difficult to teach, implicit judgment can be replaced The most common symptoms and signs of pulmo- with explicit clinical prediction