Complication Risk in Patients With COVID-19 & Thrombosis

Transcript: Gregory Piazza, MD, MS: Welcome to this HCPLive® Peers & Perspectives® presentation titled, “Antithrombosis in Patients With COVID-19.” I’m Dr Gregory Piazza, from Brigham and Women’s Hospital in Boston, Massachusetts. I’m joined by some close friends and excellent colleagues, Dr Victor Tapson from Cedars-Sinai medical center in Los Angeles, California, and Dr Alex Spyropoulos from Northwell Health in New York, New York. We’re going to discuss the prophylaxis and management of thrombosis in patients dealing with a COVID-19 [coronavirus disease 2019] infection. Welcome, and let’s get at it.

Why don’t we dive right in? We have a number of fantastic discussion points and questions, and I know my colleagues are itching to get at this. Here’s the first question. I think it’s great for Dr Spyropoulos. Alex, what risk factors make a person more vulnerable to complications if they become infected with coronavirus?

Alex Spyropoulos, MD, FACP, FCCP, FRCPC: Greg, that’s the million-dollar question, isn’t it? That’s been asked during the few months of the pandemic. The first thing to keep in mind, which is very relevant for our discussions, is that patients with underlying cardiovascular comorbidities are at increased risk of experiencing bad complications from COVID-19, especially when they’re hospitalized. Patients with underlying cardiac disease or patients who’ve had a history of stroke, diabetes, hypertension, or thrombosis are patients who tend to get into trouble, especially when they’re hospitalized.

The other thing we’re realizing more and more is that advanced age seems to be a fairly accurate predictor of a bad outcome. Our institution, Northwell Health, just published a very large database in JAMA suggesting that—also seen in China and Italy and other places—patients with advanced age are also at great risk of getting complications from COVID-19.

There are other clinical markers, and Vic and the critical-care community probably know this better than anyone. Things like DIC [disseminated intravascular coagulation] scores, SOFA [Sequential Organ Failure Assessment] scores, and SIC [sepsis-induced coagulopathy] scores, especially a score of 4 or more, also seem to portend a very poor prognosis for this hospitalized COVID-19 population. Lastly, there are key biomarkers that consistently, time and again, show that patients with these elevated biomarkers are going to run into complications. One of the most consistent biomarkers is an elevated D-dimer test score, especially when you’re using cutoffs of 4 or 6 times the upper limit of normal.

These patients tend to have poor outcomes, whether these outcomes are due to thrombotic events or events that include a coagulopathic state and highly inflammatory state. The cytokine storm that’s been described in COVID-19 is not quite known at this point. Patients with very elevated D-dimer are at risk, maybe less so with things like CRP [C-reactive protein] or troponins: these are also biomarkers that suggest poor outcomes.

Gregory Piazza, MD, MS: Exactly. Vic, tell us a little more about some of the scores you use on the frontline in the ICU [intensive care unit] to determine patients who are more vulnerable, such as a SOFA score. What goes into that?

Victor Tapson, MD, FCCP, FRCP: We use scoring to some degree. We use the parameters that Alex talked about. Sequential Organ Failure Assessment is what SOFA stands for. It’s basically a scoring system that includes a number of physiological parameters and key parameters—renal function, platelet count, things like this—that we use to score. We use it for all kinds of patients in the ICU, Greg.

When patients get to the ICU, it depends on how you admit patients at your center. At some centers, you’re overloaded with patients, and some of the sicker people can’t even get in the ICU right away. Some people come in on 6 L of oxygen, some people come in on high-flow oxygen, and some people come in and are intubated on the floor. But once they get to the ICU, there’s generally some sort of significant respiratory stress involved. Almost everyone has bilateral pulmonary infiltrates. Some of them are minimal. Some of them are more significant. It’s been striking to me. Currently, I’m the site PI [principal investigator] for the NIH [National Institutes of Health] remdesivir trial at Cedars-Sinai, so I see a lot of these folks come into the ICU who have pulmonary infiltrates.

One of the criteria to get into the study is hypoxemia and pulmonary infiltrates. It’s interesting to me how often patients are very hypoxemic with pulmonary infiltrates. Why are they so sick? Why are they so hypoxemic when their x-ray doesn’t look that bad? On the other hand, we’ve seen some really severe ARDS [acute respiratory distress syndrome] pictures, as well. As Alex pointed out, everybody’s ferritin seems to be in the 1000 μg/L range when they’re sick. CRP levels are very, very high. The IL-6 level is very, very high. The D-dimer levels come in higher than we often see in patients with acute pulmonary embolism. We see these inflammatory markers and D-dimer levels together. Then you see hypoxemia and sometimes shock.

Many of us are thinking, Greg, that this is a DIC microvascular thrombosis picture. We need more data, I think, to support exactly what’s going on. But patients come in sick, hypoxemic with pulmonary infiltrates—sometimes out of proportion to the hypoxemia—and sometimes hemodynamic problems requiring pressures.

Gregory Piazza, MD, MS: Alex did a really nice job of talking about the comorbidities and factors that go into managing these complicated patients. If you were to describe the type of patient you see coming into your ICU, what does that person look like? Is it predominantly an older patient with lots of comorbidities? Give me the spectrum.

Victor Tapson, MD, FCCP, FRCP: The spectrum is pretty wide. I’ve been on the PERT [pulmonary embolism response team] for the last month evaluating patients with and without COVID-19, so I’m not on the frontline in the ICU right now. I really respect my younger colleagues and the nurses and the respiratory therapists in there treating this. Greg, regarding what patients look like when they come in, Alex is absolutely right. Age is clearly a risk factor. We have 80- and 90-year-old patients in the ICU, and we’ve gotten some of them out and off the ventilators. But that’s optimistic. It’s a bad disease.

We have a 20-year-old in the ICU right now and a 40- and 41-year-old, 3 men. Men seem to be getting hit with this a bit more. Young people can get this. I have not seen a teenager with it yet. I’ve not seen anyone under age 10. Age really does seem to be protective to some degree, but it is not universal. I don’t know if it’s because of the viral load, but we’ve seen some very sick younger patients.

Gregory Piazza, MD, MS: Yes, certainly we’re learning that none of us should feel too comfortable about our odds if we were to get COVID-19. There is no immortality bias here.

Transcript Edited for Clarity