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Diagnostic utility of D-dimer concentrations in dogs with pulmonary embolism | VETgirl Veterinary Continuing Education Podcasts

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In today’s VETgirl online veterinary continuing education podcast, we review the use of D-dimers in predicting the presence or absence of pulmonary emboli in dogs. Pulmonary embolism (PE) refers to an obstruction of a pulmonary vessel, which could be caused by a blood clot, tissue, infectious material, parasites, foreign bodies, or other material (Goggs). There are a variety of diseases known to increase risk for PE’s in our canine patients, including immune-mediated diseases such as IMHA, protein-losing nephropathies, hyperadrenocorticism, neoplasia, sepsis, and cardiac disease, as well as the use of certain medications like steroids. Unfortunately, the diagnosis of PE can be challenging due to non-specific clinical and radiographic changes. Probably many of us have seen an IMHA patient become acutely dyspneic with minimal radiographic changes, a situation where you may highly suspect a PE! In human medicine, CT or pulmonary angiography are the gold standard for antemortem diagnosis (Torbicki), but there have been various studies in both humans and in dogs evaluating the use of D-dimers as a tool to rule out a PE.

So what are D-dimers? D-dimers are degradation products of cross-linked fibrin. That means that the levels of D-dimers in the blood will increase with increased formation of clots and increased breakdown of clots (fibrinolysis) in the body. Unfortunately finding elevations in D-dimers are not specific for a pulmonary embolism, but low D-dimer values have been considered as a tool to rule out this condition.

So, Epstein et al from UC Davis wanted to evaluate how useful D-dimer values are in their study called “Diagnostic Utility of D-Dimer concentrations in Dogs with Pulmonary Embolism.” This was a retrospective study assessing the diagnostic utility of D-dimers in dogs with pulmonary embolism. The authors included dogs with a necropsy-confirmed pulmonary arterial thrombus or embolus, and who also had a coagulation panel that contained a D-dimer value performed at the same visit in which the patient was euthanized or died. Dogs were excluded if they were in DIC or had thrombi in organs other than the lungs on necropsy. The study also included a control group that were age, sex, and breed-matched. The control group included dogs that had D-dimers measured, did not have pulmonary thrombi or infarction on necropsy, and that were not in DIC. The investigators then collected the patients’ signalment, location and distribution of pulmonary emboli, as well as PT, aPTT, fibrinogen, and D-dimer levels from the medical record for analysis.

A total of 10 dogs were identified that fit the inclusion criteria. Underlying diseases included neoplasia, renal disease, sepsis, cardiac disease, immune-mediated hemolytic anemia, and in one dog an unknown disease process. Of the 10 control dogs, diseases included neoplasia, renal disease with PLN, seizures, sepsis, gallbladder rupture with bile peritonitis, and pulmonary hypertension secondary to chronic bronchitis. Two of the control dogs were found to have systemic thromboembolic disease on necropsy. The majority of dogs with PE had multiple lung lobes involved, with a 50:50 mix of large versus small arteries being affected.

So what did these investigators find? When comparing the dogs with PE and the control group, there were no statistically different findings in PT, aPTT, fibrinogen, or D-dimers. In looking at D-dimers above the high end of the reference range, which in this laboratory was 250 ng/mL, their sensitivity for PE was 80% with a specificity of 30%. There was not a significant difference in the proportion of dogs with elevated D-dimers between groups. In other words, this test has very poor specificity for diagnosing PE in dogs! The sensitivity was high at 80%, but this value is still lower than what has been previously reported in people. This means that of the 10 dogs with a confirmed PE, 8 dogs had elevated D-dimers, whereas 2 dogs did not. As a quick reminder, the negative predictive value (NPV) indicates how likely it is for a patient who tests negative to truly not have the disease (ie, a true negative). In this study, the NPV was 60%, also lower than what has been reported in people. Another way of looking at it? In this population, the D-dimer value would have to be less than 103 ng/mL in order to achieve 100% sensitivity.

The authors listed a few limitations to their study, which included small sample size, variations in the type of D-dimer assay used, the potential that PEs could have been missed on necropsy in the control group, and the presence of systemic thromboembolic disease in 2 control dogs.

So what can we take away from this VETgirl podcast? D-dimers can be used as an adjunctive tool when there is suspicion of a PE, but unfortunately low values cannot completely rule out the presence of PE. However in this study, D-dimers less than 103 ng/mL were able to achieve 100% sensitivity in ruling out PE, so if your patient does have a value below this, perhaps a PE is less likely. In short, this study demonstrates that PE’s can be troublesome to diagnose, and it is still critical to assess your patient as a whole, including the presence of known risk factors, presentation and clinical progression, radiographic or other imaging findings, ability to oxygenate, and last but not least, D-dimers and other coagulation parameters.

References:
1. Epstein SE, Hopper K, Mellema MS, et al. Diagnostic utility of D-dimer concentrations in dogs with pulmonary embolism. J Vet Intern Med 2013;27:1646-1649.
2. Goggs R, Benigni L, Fuentes VL, et al. Pulmonary thromboembolism. J Vet Emerg Crit Care 2009: 19(1):30-52.
3. Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2008;29:2276-2315.

Abbreviations:
aPTT – Activated partial thromboplastin time
DIC – Disseminated intravascular coagulation
NPV – negative predictive value
PE – Pulmonary embolism
PTT – Prothrombin time

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