SCCM Resource Library-COVID-19 Hypercoagulability: Lessons Learned

Video Transcription

Hello. Welcome to A Closer Look at Coagulopathy in COVID-19 Patients. I'm Dr. Marilyn Bullock and I'll be your moderator for today's session and the speaker for our first topic,  COVID-19 Hypercoagulability Lessons Learned. Now this topic is to discuss general lessons learned and maybe not all of them are exclusive to coagulopathy.  One of the lessons that we had to learn, or at least remember, was that viruses can activate the bronchioavular hemostatic system.  And this is part of our natural defense system and localized thrombi formation in the lungs  can actually be a positive response and may not require treatment in the absence of respiratory compromise. What we've seen in COVID-19 is that pulmonary thrombosis load is lower  and the distribution of clots is more in the peripheral pulmonary arteries. If our body's immune systems can clear the virus,  then the lungs' vigorous fibrillinic system can break down localized clots, which will re-enable normal gas exchange.  However, when you have continued inflammation, that can lead to pulmonary thrombi formation,  which can disseminate into our systemic circulation and cause thrombi in our circulatory beds.  There are two situations where the viral infection can cause systemic coagulation activation. The first is when you have a high viral load that causes a heightened immune response,  leading to extensive coagulation activation and ultimately thrombi in different circulatory beds.  The second is when you have a moderate viral load, but a very aggressive immune response.  The next lesson is that the intersection between the immune system and the hematologic system should not be forgotten.  Platelets are more than just something to help our patients clot. They have a role in inflammation and infection and have a suicidal role in our efforts to kill the pathogens.  These pathogens can try to evade detection by the immune system by hiding in platelets. Well, the platelets then look abnormal, so they get cold by the spleen.  Now, when do we intervene? We don't know. If we intervene too early, you might lose the benefit of the platelets,  and if you intervene too late, your patient might develop thrombocytopenia.  We know that in critically ill patients, underlying thrombotic and inflammatory damage can be too advanced to be affected by high-dose therapies.  What we know is that we still need practical, mainstream biomarkers for platelet activation, other than just using platelet counts in our routine clinical practice.  The third lesson is that a novel pathogen can have historical clues that we could and should look to when trying to anticipate potential complications.  In SARS at the beginning of the 21st century, thrombi were seen throughout the lungs in post-mortem patients, as were pulmonary embolisms, DVTs, and widespread multi-organ infarcts.  Up to 55% of patients had a decrease in platelets, with the lowest platelet count occurring about a week after onset.  These patients also had increases in D-dimer and prolonged activated PTT. Up to 2.5% of all SARS patients had ischemic strokes, and 30% of critically ill patients had a VTE.  In MERS, up to 36% of patients had a decrease in platelets. Now it's more common, it was mild in the first week, without a big difference in patients who had mild or severe MERS,  but in fatal cases, DIC was a major complication, and microthrombi were present by day four of illness in some patients.  The fourth lesson is that the D-dimer is more than a pertinent negative.  Now we know that this is increased in many diseases, but there's a known correlation between high D-dimers and clots,  and it's one of the few consistent abnormal coagulation markers in patients with thrombosis.  So it can still be helpful to us in patients with COVID-19, even if it doesn't indicate thrombosis. The inflammatory process can generate D-dimers from extravascular fibrinolysis.  D-dimers have been consistently shown to be a prognostic marker in COVID-19, and its predictive capacity is independent of our patient's thrombotic risk.  It also correlates with acute lung injury. A worsening D-dimer may tell us that our patient needs more aggressive measures  in order to prevent acute lung injury while our patient is still stable, and improving D-dimers may tell us that we need to consider tapering treatment modalities.  Our fifth lesson, not exclusive to coagulopathy or COVID-19, is that published research is not always peer-reviewed.  We should all be familiar with the normal peer-review publication process, which is meant to be a safety net and ensure only the highest quality research  and information is disseminated regarding medicine. But when COVID-19 first appeared, we didn't have any information about it at all.  We were just trying to find quick and efficient ways to share what we were learning. And so we went through the usual research and manuscript development,  but then it could be uploaded to a preprint server like MedArchive, where it was available with a digital object identifier, or a DOI, for anyone to access.  Now the authors could then go on to submit it to a journal, where it would go through the normal peer-review publication process, but not all of them did.  However, the information was still out there for everyone to see, whether it had gone through that safety net process or not.  The first preprint for COVID-19 was published back in January 19, 2020, and it's still being uploaded today. The reason this is important is that the early studies of COVID-19  facilitated our confusion about the virus and how to manage it. We embraced pragmatic designs meant to reduce the burden of participation.  We saw small numbers of patients, open-labeled medications, and shortened or automated data collection, often resulting in incomplete and inconsistent data.  The studies tended to focus on therapies with pre-existing regulatory approval, which reduced the level of regulatory oversight.  It also enabled hospitals without extensive research experience to participate in order to maximize patient recruitment.  Unfortunately, the differences in care and research standards across countries often led to data and results that were not always reproducible.  There have been several proposed solutions to the research issues we've seen with COVID-19. The first is to create national or even international registries for emerging diseases  that would work both during and outside of pandemics, and would collect data from hospitals within a jurisdiction,  whether that be at the local, national, or even international level, and allow us to look at more patients or more data points.  There are those who advocate for national EMRs for easier data collection and even national audits or registries for critical illness.  To deal with the fact that we've had too many small trials that were underpowered with inconclusive research,  one of the solutions is to coordinate data collection between clinical trial networks that prioritize multi-center studies.  To decrease the number of competing or overlapping trials, we should promote collaboration across trial networks and funding agencies  to generate larger data sets and prioritize adaptive platform trials to enable parallel testing of multiple therapeutic options.  Finally, there's a lot of bureaucracy that can delay setting up clinical trials.  One of the solutions proposed to deal with this is to create national or regional ethics boards or IRBs.  We've also been reminded that occasionally bad studies still manage to slip through the peer-reviewed process  and get published in a peer-reviewed journal where it's accessible to all of us and our medical colleagues. Almost 200 COVID-19 studies have been retracted to date.  There's been a lot of reasons for retraction, everything from duplication to breach of policy.  Sometimes there's been objections to the results or conflicts of interest, even plagiarism, and then limited or no information.  Sort of surprising that they managed to make it through the peer-reviewed process to begin with, but they did.  Unfortunately, while many people may pay attention to when an article is published, they're not always aware of when it's retracted.  We're not only dealing with a pandemic, but we're in the midst of an infodemic of COVID-19 research. Let's face it, data's dull, and infographics can take that data  and package it into pretty, easily-to-digest pictures that can be posted anywhere, not just for us as healthcare providers, but for our patients and the general public as well.  And the graphs in the infographics can be accurate representations of the data, but they can just as easily be inaccurate.  So it's important to look at who published it, and does it come from a credible source? You also want to think, how do those results fit in with what we already know?  When the pandemic first started, we didn't know anything about the virus or what to expect. In two and a half years, we've learned a lot of information,  and it's important that the results fit with our current body of knowledge. You don't want to discount single studies automatically,  because single studies can be helpful as an important step forward, and we know that studies are more informative when they build upon previous research.  But at some point, there should be more than one study that guides our evidence-based practice. You also want to think about how credibility and biases play in.  Funding and preconceived notions can affect credibility, and unfortunately, we've seen cases where research had a preconceived hypothesis that they were determined to prove.  Our next lesson is that research we're applying to critically ill patients best comes from those who are actually critically ill. In COVID-19, particularly with coagulopathies,  we've seen a lot of research conducted in hospitalized patients in general, which then we try to extrapolate to just our ICU patients, and the outcomes are not the same.  We have to remember that our patient population is unique. It has unique variables that influence how our patients are going to respond and react.  Now that we're two and a half years in, going forward, we want to try to make sure that any data we're using comes from the group of people that we're actually providing care to.  The last lesson I want to leave you with is that it's going to take time for us to understand COVID-19.  The virus is only two and a half years old, and we've got a lot left to learn about it. Let's think about the Dunning-Kruger effect.  This is a phenomenon that tests a human psychological trait many have witnessed before. Think about it. We've all seen other infections. We've all managed other infections.  Under this phenomenon, those with below-average knowledge or skills tend to overestimate their own abilities.  They can be particularly dangerous because they may not recognize the risk associated with it, or even worse, they may recognize the risk,  but think that their skills and knowledge is sufficient to handle it when it's not. Now, with time and more experience, we realize we don't know as much as we thought we did.  Unfortunately, that's when confidence starts to decline. But with more experience and more time, that confidence will grow again  until you have a perfect balance of experience and confidence. And once again, you'll be back at expert level. That's going to happen. It will, but it is going to take some time.  With all of those lessons learned, let's take a closer look at coagulopathy and COVID-19. I'm going to pass you on to our other renowned faculty who will discuss the physiology,  pathophysiology, and mechanisms of disease, anticoagulation, and we'll finish up with hyperviscosity. Thank you.

Video Summary

In this video, Dr. Marilyn Bullock discusses various lessons learned about coagulopathy in COVID-19 patients. One important lesson is that viruses can activate the body's natural defense system called the bronchio-vascular hemostatic system, leading to thrombi formation in the lungs. This can be a positive response if there is no respiratory compromise. However, ongoing inflammation can cause pulmonary thrombosis and the formation of clots in the circulatory system. Another lesson is the role of platelets in inflammation and infection. The timing of intervention in platelet-related complications is crucial. The video also highlights the significance of D-dimer as a prognostic marker in COVID-19. Additionally, the video discusses the challenges of navigating through the vast amount of COVID-19 research, including unpublished preprints and retracted articles. It emphasizes the need for credible sources and the importance of incorporating research from critically ill patients into clinical practice. Finally, the video emphasizes the need for time and experience to fully understand COVID-19 and the importance of balancing confidence with expertise.

Asset Subtitle

Infection, Hematology, 2022

Asset Caption

COVID-19 has been shown to infect endothelial cells, which, along with inflammation, can lead to a hypercoagulable state. This session will review the pathophysiology of endotheliopathy and perturbation of coagulation in COVID-19, screening strategies for deep vein thrombosis and pulmonary embolism, evidence about timing and dosing of prophylactic and therapeutic anticoagulation, evidence for hyperviscosity, and the role of cytokine release in altered coagulation. Lessons learned from the COVID-19 pandemic may be applicable to other critically ill patients.

Meta Tag

Content Type Presentation

Knowledge Area Infection

Knowledge Area Hematology

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Coagulation

Tag COVID-19

Year 2022

Keywords

coagulopathy

COVID-19

thrombi formation

platelets

D-dimer

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