D-dimer is a specific fibrin degradation product that has been widely studied in patients with acute DVT and PE. The rapid enzyme-linked immunosorbent assay is the most commonly used method for measurement of D-dimer. When used in conjunction with a low clinical pretest probability for VTE, D-dimer testing is very sensitive and has a high negative predictive value in excluding the presence of DVT. Several studies have shown that D-dimer testing can decrease the need for further testing such as repeat venous ultrasonography. However, the specificity rates of D-dimer testing are low particularly in patients with cancer, pregnant women, and hospitalized and elderly patients.
Arterial blood gases (ABG) have a limited role in diagnosing acute PE. In those with PE associated with hemodynamic instability, the ABG typically shows hypoxemia with an increased alveolar-arterial (A-a) gradient. However, in the PIOPED study, 7% of patients with angiographically documented PE had completely normal ABG measurements. Due to the increase in minute ventilation, patients with PE can demonstrate normal or decreased pCO2 and respiratory alkalosis.
Elevated levels of serum troponin I or T are noted in 30% to 50% of patients with a moderate or large PE and can indicate RV strain, ischemia, or impending myocardial infarction and are predictive of a poor outcome. One meta-analysis showed that elevated levels of troponin were associated with an increase in the short-term risk of death by a factor of 5.2 (95% confidence interval [CI], 3.3-8.4) and an increase in the risk of death from PE by a factor of 9.4 (95% CI, 4.1-21.5).
BNP (and its precursor, N-terminal pro-BNP) are released in response to increased cardiac filling pressure and are frequently elevated in patients with significant PE. Similar to patients with PE who have elevated troponins, patients with elevated levels of BNP and pro-BNP have an increased risk of an adverse in-hospital outcome as compared with patients with normal levels.
Algorithms for DVT and PE
Validated algorithms are important to evaluate patients with suspected DVT along with objective testing to confirm the diagnosis. Risk factors for DVT should be identified including malignancy, recent surgery, history of prolonged bed rest or immobilization, obesity, lower extremity trauma, pregnancy, and use of oral contraceptives or hormone replacement therapy. The 2012 American College of Chest Physicians (ACCP) consensus guidelines recommend the following goals for nonpregnant patients with a suspected first DVT of the lower extremity: reduce overall false negatives to 2% or less as defined by symptomatic DVT or PE within 3 to 6 months after a negative test; reduce the risk of fatal PE after testing less than 0.1%, and reduce the risk of fatal hemorrhage due to anticoagulation to less than 0.1%. The guidelines endorse using the Wells score for risk stratification of patients for likelihood of DVT into low-, moderate-, and high-risk categories. The Wells criteria for DVT include risk factors, such as active cancer, bedridden recently more than 3 days or major surgery within 4 weeks, calf swelling more than 3 cm compared to the other leg, collateral superficial veins present, entire leg swollen leg, localized tenderness along the deep venous system, pitting edema greater in the symptomatic leg, previously documented DVT and alternative diagnosis to DVT as likely or more likely. Wells score of 4 or less is consistent with a low (5%) pretest probability for DVT; 4.5 to 6 is consistent with a moderate (17%) pretest probability, and more 6 with a high (53%) pretest probability of DVT (Table 20–1).
Table 20–1Wells criteria and pretest probability of DVT. ||Download (.pdf) Table 20–1 Wells criteria and pretest probability of DVT.
|Wells Score ||Probability of DVT |
|Low ||5% |
|Moderate ||17% |
|High ||53% |
In patients with a low pretest probability for DVT in the leg, the guidelines recommend checking either a moderately or highly sensitive D-dimer and compression ultrasound of the proximal leg veins rather than whole leg ultrasound. D-dimer testing is preferred over compression ultrasound of the proximal veins as the initial test. If D-dimer is negative, no further testing is necessary; if D-dimer is positive, compression ultrasound of the proximal leg veins should be performed, and if this is positive, then the patient should be treated without further testing.
In patients with a moderate pretest probability for DVT in the leg, the guidelines recommend checking either a highly sensitive D-dimer (unless the patient has a comorbid condition that would likely elevate the D-dimer level, such as cancer or recent surgery or trauma), compression ultrasound of the proximal leg veins, or whole leg ultrasound. If the highly sensitive D-dimer is negative, then no further testing is needed. If the highly sensitive D-dimer is positive, then compression ultrasound of the proximal leg veins or the whole leg is recommended. A negative ultrasound should lead to a repeat compression ultrasound in 1 week and checking a moderate/high sensitivity D-dimer. If the compression ultrasound is negative, no further testing is warranted. If the D-dimer test is negative, no further testing is needed. If whole leg ultrasound is chosen and is negative, no further testing is also recommended. If compression ultrasound of the proximal leg veins or whole leg ultrasound is positive, the patient should be treated without further testing. If whole leg ultrasound is only positive for isolated distal (calf vein) DVT, serial ultrasounds are recommended to ensure the DVT does not propagate proximally rather than treating with anticoagulation. Approximately 15% to 20% of calf vein thrombi can extend into the proximal veins especially within the first 7 days; thus the need for serial ultrasound examinations.
In patients with a high pretest probability for DVT in the leg, the guidelines recommend either compression ultrasound of proximal leg veins or whole leg ultrasound. If either ultrasound examination is positive, the patient should be treated without further testing. If the whole leg ultrasound is negative for DVT, no further testing is recommended. If the compression ultrasound of the proximal leg veins is negative, one can either repeat the ultrasound in 1 week and if negative no further testing is recommended, or check a high sensitivity D-dimer and if negative, no further testing is needed. If D-dimer is positive, repeat compression ultrasound in one week is recommended and if negative, no further testing. D-dimer should not be used as a stand-alone test to rule out DVT in patients with a high pretest probability for DVT.
A diagnostic algorithm (Figure 20–1) with a dichotomized version of the Wells clinical decision rule, D-dimer testing, and CT has been shown to be useful in guiding management decisions in almost 98% of patients with clinically suspected PE.
Diagnostic algorithm in patients with clinically suspected PE. (Reproduced with permission from Pastores SM: Management of venous thromboembolism in the intensive care unit, J Crit Care. 2009 Jun;24(2):185-191.)