Differentiating the etiology of pulmonary diseases

In this video, from our Inflammatory Marker Essentials course, we review utilizing inflammatory markers to differentiate between deep vein thrombosis (DVT) and pulmonary embolism (PE). The use of inflammatory markers in these conditions can be separated into two clinical questions—learn about them by watching!

Inflammation got you all flustered? With this course, you'll master the use of inflammatory markers to get to the right diagnosis.

Clinicians encounter inflammation daily and there are lots of inflammatory markers to consider. Which should you order for your patient? Here, you’ll learn the strengths and limitations of each marker, when they’re useful, and when they’re not. We’ll look at laboratory markers of inflammation as well as radiologic and clinical signs so you can take your diagnostic skills to the next level.

Venous thromboembolisms, VTE, which includes deep vein thrombosis, DVT, and pulmonary embolism, PE are other conditions driven by the inflammatory response. The use of inflammatory markers in these conditions can be separated into two clinical questions. One, in a patient that presents with shortness of breath and or lower extremity edema, what is the likelihood of having VTE disease? And two, in patients with known VTE disease, what is the likelihood of recurrent disease? For patients that have a low pretest probability of disease, the use of inflammatory markers like D-dimer have become the routine first step in determining the need for further testing.

Elevations in this nonspecific inflammatory marker make it more likely that VTE disease should be considered and tips a balance of further testing towards beneficial. A normal or low result, on the other hand, would tip the balance towards increased risks and or costs that do not warrant further testing. The initial assessment of risk for VTE is helpful in two respects. First, diagnostic confirmation of DVT or PE may not be easily accessible. For instance, not every clinical facility has a Doppler ultrasound machine for evaluation of DVT. The accessibility of CT or ventilation perfusion scanning or VQ scanning is rarely available in a primary care setting. Rapid evaluation with these tests would require redirecting the patient somewhere else, like the emergency department.

Second, even if the patient initially presents to a location that has these tests readily available, the benefits of diagnosis must be balanced with potential risks. Contrast can induce nephropathy in the case of CT scans, and these tests increase costs. It is important to note two things. The assessment of pretest probability should not be done entirely subjectively. The assessment of VTE disease is notorious for being influenced by numerous cognitive biases. For instance, if the last four patients similar to this one, presented with a swollen leg and shortness of breath, and had a negative CT pulmonary angiogram, you are more likely to think that this patient does not have PE as well.

So, the use of standardized risk stratification scores is crucial in mitigating any of these cognitive biases that might affect our judgment. There are numerous risk scores that have been validated, including wells, Padua, and caprini scores. It is beyond the scope of this lesson to cover the specifics of these scores. The second consideration is that D-dimer should only be used in situations with low pretest probability. If a patient has all of the typical signs and risks of PE, such as shortness of breath, and tachycardia with a new diagnosis of colon cancer, then D-dimer plays no role in evaluation for VTE and further testing like CT should be performed. This is because in the case of intermediate and high pretest probability, the result of the D-dimer does not reclassify risk of VTE disease, said another way, you would have to get further testing whether the D-dimer is low or high, so you might as well skip it.

As mentioned earlier, the use of inflammatory markers is also helpful in patients who have known VTE disease. A longer time in anticoagulation reduces the overall risk of DVT PE disease by delay the onset of recurrent DVT PE disease. But long term anticoagulation poses a number of problems. The longer you are on anticoagulation, the higher you bleeding risks, while the longer time on anticoagulation would reduce the risk of recurrent VTE disease. The simultaneous rise in bleeding risk could in certain patients rise to a point to negate any benefit. The use of inflammatory markers can help determine if some patients are likely to fall into such a situation.

One approach is to use inflammatory markers to diagnose syndromes like antiphospholipid syndrome with known high risk for recurrence. Antiphospholipid syndrome is associated with several antibodies, rather than a single one. This necessitates the use of a panel of several different inflammatory markers and antibodies rather than a single test. The most common markers included are the auto antibodies against cardiolipin and beta-2 glycoprotein. Of note, the lupus anticoagulant panel is a misnomer, as it does not directly measure any antibody. Instead, it measures the auto antibodies effect on clotting indirectly. Another approach is to measure the presence of ongoing inflammation, which correlates to increased risk of recurrence.

The duration of anticoagulation for the vast majority of patients is relatively clear, based on the historical factors like the presence of malignancy, or whether the DVT was provoked or unprovoked. It is beyond the scope of this lesson to cover the details of these decisions. However, there are definitely cases where their decision to stop anticoagulation relatively early or prolong it is not as clear cut. This may be due to patient preferences, or due to concern about risk benefit ratio. It is this clinical situation where inflammatory markers can be of use. The most common situation is a patient with a first episode unprovoked DVT. The most common inflammatory marker used in this way is D-dimer. A sustained elevation in D-dimer may predict a higher risk of recurrence in VTE, and therefore signal the need for longer term anticoagulation than previously planned.