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[upbeat intro music][Dr. Handy] Hi, welcome to Harrison's PodClass, where we discuss important concepts in internal medicine.

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I'm Cathy Handy. [Dr. Wiener] And I'm Charlie Wiener, and we're coming to you from the Johns Hopkins School of Medicine.

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[Dr. Handy] Welcome to episode 95. Today, we're talking about five patients with dyspnea.

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[Dr. Wiener] Hey, Cathy. Well, today we have another group of patients who need your help.

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[Dr. Handy] All right, I'm ready. [Dr. Wiener] So, I'm going to present to you five patients, all of whom present to the emergency department with acute dyspnea.

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And the discussion is going to be about D-dimer testing, because a D-dimer test is ordered for all of them.

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And let's first talk about the D-dimer test itself.

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[Dr. Handy] Okay, so recall that to balance our thrombosis or coagulation cascades that lead to fibrin generation, there's a fibrinolysis cascade that is initiated by plasmin.

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The D-dimer is one of the fibrin degradation products and consists of two cross-linked fibrin fragments.

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It does not normally circulate in plasma, so its presence suggests that fibrinolysis is occurring somewhere in the body, although it's often clinically ineffective thrombolysis.

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The trouble with the test is that while it's very sensitive for thrombosis, it's really not specific.

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So the clinical context and the pretest probability are important when you're ordering and then also subsequently interpreting the test results.

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[Dr. Wiener] So, when you say that it's sensitive but not specific, you mean that a negative D-dimer assay in a patient suspected of pulmonary embolism is helpful in that it has a strong negative predictive value, i.e., they don't have a PE, right?

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[Dr. Handy] Right, A negative test helps rule out PE, but the positive test is far from diagnostic.

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And if the patient has a high suspicion of PE, they'll need a diagnostic test, such as a PE protocol CT.

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So, let's go into the patients now.

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[Dr. Wiener] Okay, so as I mentioned before, all of these patients are presenting to the emergency department with new acute onset dyspnea.

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The question is asking, in which of the following patients would a positive D-dimer be helpful in prompting additional imaging to diagnose pulmonary embolism or DVT?

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So the five patients are, Patient A. is a 24-year-old woman who is 32 weeks pregnant.

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Patient B. is a 48-year-old man with no past medical history and presents with calf pain following prolonged air travel.

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His room air oxygen saturation is 96%.

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Patient C. is a 56-year-old woman undergoing chemotherapy for breast cancer.

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Patient D. is a 62-year-old man who underwent hip replacement surgery four weeks ago.

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Patient E. is a 72-year-old man who had an acute myocardial infarction two weeks ago.

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And remember, all of these patients are presenting with acute onset dyspnea.

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[Dr. Handy] And all of the patients that you mentioned have risk factors for PE.

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However, the only patient where D-dimer would be helpful is Patient B.

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So that's the man with no past history, who has a strong story that would be suggestive of DVT/PE because of the air travel and then now presenting with focal calf pain.

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So, he's the only one of those patients who is likely to have a negative D-dimer at baseline, sort of before this presentation, so doing one now would be helpful.

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[Dr. Wiener] But wait, he has an oxygen saturation of 96%.

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Doesn't that rule out PE? [Dr. Handy] Well, it's absolutely true that patients with acute PEs often have V/Q mismatch and may present with hypoxemia.

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However, the more common abnormality is a respiratory alkalosis or hyperventilation.

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So they will very likely have a reduced arterial PCO2 and if we remember the alveolar gas equation, his alveolar oxygen will be increased with the reduced alveolar CO2.

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So his arterial oxygen could be normal.

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Now the amount of V/Q mismatch is variable, and a normal A-a gradient may be present with the PE.

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[Dr. Wiener] Okay, so if the D-dimer is not elevated, he likely does not have a PE and does not require further additional testing?

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[Dr. Handy] Correct. [Dr. Wiener] Okay, well, tell me why the other patients are likely to have an elevated D-dimer at baseline, such that additional testing for them is not useful.

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[Dr. Handy] So in all the other scenarios, elevations in D-dimer could be related to other underlying medical conditions and provide no diagnostic information to really inform the clinician regarding the need for further evaluation.

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So, some common clinical situations in which the D-dimer is elevated, would include sepsis, myocardial infarction, cancer, acute or chronic pneumonia, recent surgery, or just being in a postoperative state, and the second and third trimesters of pregnancy.

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[Dr. Wiener] Okay, so regarding our patients, patient A. is pregnant, patient C. has breast cancer, patient D. had recent surgery, and patient E. had an MI or a thrombotic event within the past month.

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All of those folks would be expected to have an elevated D-dimer when they arrive at the ED, with or without a PE, right?

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[Dr. Handy] Right, so even if they don't have PEs, the likelihood of an elevated D-dimer is high.

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[Dr. Wiener] So what do you do with those patients then? [Dr. Handy] Yeah, so if you have a patient with a suspected PE, who has a high pretest probability of an elevated D-dimer, you'd need to perform a more specific diagnostic test for PE, such as a contrast chest CT or a lower extremity Doppler if you're looking for a DVT.

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[Dr. Wiener] Great, so the teaching point in this case is that in carefully selected outpatients with suspected pulmonary embolism, a D-dimer test may be useful in that a negative D-dimer can rule out pulmonary embolism in a patient who is not expected to have a pretest probability of a positive D-dimer.

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However, in that context, the test should not be used in patients with underlying diseases or underlying conditions that make it likely they have a baseline elevated D-dimer, which would be positive regardless of whether or not they have a new DVT or PE.

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[Dr. Handy] And you can read more about this in Harrison's chapter on pulmonary embolism.

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[upbeat outro music][Mr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill.

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