I'm Michelle Loy. I'm one of the faculty members at the University of Colorado, dual trained in HEMOC and critical care. And I'm going to be presenting these slides on behalf of Julie Jaffrey, who is an associate professor in San Diego. She's also the co-lead for the chat database that we're going to talk about shortly here. And she's also the author of several prominent papers on pediatric VTE risks factors. I have no disclosures. So why is pediatric VTE worthy of discussion? I think the fact that you guys are all in this room know the answers to this. So the reason why we care about pediatric VTE is because of the severity of the end sequelae of these events. So VTE recurrence progression can occur up to 21% of patients who have already sustained a primary VTE. Embolism can occur in up to 16% of these patients and 2% of these patients will die from their VTE. Greater than a quarter of these patients will suffer from post-thrombotic syndrome. And then there's also morbidity from treatment. In addition to the bleeding and bruising you can have from anticoagulation treatment, you also have all the clinic visits that you need to monitor that anticoagulation. There's also administrative concerns. So pediatric VTE is the second leading cause of serious harm in this population. And children diagnosed with a VTE while hospitalized have an additional 8.1 hospital inpatient days. This was a study done a few years ago but it costs on average an excess of $27,000 more per hospital stay. And some insurance companies are refusing to reimburse for hospital-acquired conditions. And as this becomes more consistent in pediatrics I think that hospital leadership will start to care if they haven't already. So what risk factors put children at risk for getting a hospital-acquired VTE? So a lot of these risk factors are similar to our adult population. There's central lines, inflammatory conditions, just being acutely ill. You can be post-surgery or have immobility from another reason. And a lot of these factors I think you guys have seen before so I won't read them all out loud. The most significant of these risk factors is just requiring hospitalization in the first place. You get your risk augmented if you're in the critical care units. And then if you have a central line that's also one of the main risk factors. So the incidence of hospital-acquired VTE in critically ill children is 2%. And in children that are critically ill and also have a central line, 18% of them will have asymptomatic VTE. So that's in addition to all the patients that already have symptoms from another VTE event. So a lot of you all can also recall this seminal paper done by Dr. Leslie Ruffini at CHOP in 2009 where she looked at the Pediatric Health Information Systems Database and looked at the rise in the rate of hospital-acquired VTE from 2001 and 2007. At that time, we saw that the rise was 70%, which is astronomical at the time. Dr. Sarah O'Brien and Dr. Leslie Ruffini and their collaborative groups looked at this data again in 2020 to see if the rate of rise was continuing or if it was plateauing. And what they found in this 11-year time period that they looked at it is across all age groups, there's actually an 130% increase in VTE rate. So this is an update for you all from that seminal paper. So we should care because it's only getting worse. Of these risk factors, we're learning that one of the most prominent risk factors is having a central venous line. So 80% of these thrombosis events are in children who have a central venous line. And in children that have a central venous line place, three to 34% will develop a clot. So a lot of you guys are wondering, is this true? Do a third of my patients get clots whenever I place a central line? And you're probably right, it's not totally true or true to life because we have to think about the heterogeneity across these studies. Some of these studies look at patients that are higher risk for clots than your general ICU population. Some of them will look at different central line types. And a lot of them will also look at surveillance imaging, which by ultrasound or venograms will pick up asymptomatic VTEs as well, which is not a clinical practice. We don't ultrasound every single person that we put a central line in. We usually do it when they get symptoms. So central lines will augment two areas of your VUCOWS triad. So you'll have endothelial damage due to catheter insertion, and you'll have venous stasis just by virtue of having an extra thing in your blood vessels. And the patient provides that hypercoagulability condition that will allow you to form a clot. So if we know that central lines are one of the most prominent risk factors, are there certain types of lines that are put you at even higher risk? And in this review paper by Dr. Julie Jaffray and Dr. Neil Goldenberg, lines that put you at highest risk is PICC lines, perhaps due to the large surface area of endothelium that's covered by the PICC line. Non-tunnel femoral lines, perhaps due to the angle of your insertion. Multiluminal catheters, because they're thicker. Percutaneous insertion causes more risk than a cut down. Subclavians, more than jugulars. And if you have any malfunction in your central venous catheter or a CLABSI, that will also predispose you to having more clot there. Looking at the patient population, cancer, congenital heart disease, and neonates really lead in terms of risk factors in the patient population. So looking at risk assessment models, this is a standardized way of assessing risk in the adult population. But even when we know all of these risk factors, there's not really a great way of doing risk assessment modeling in pediatric patients. So the reason for this is a lot of the studies looking at these risk assessment models have been single institution and not externally validated. So Dr. Branchford in 2012 looked at 78 cases, 160 controls, and he looked at all comers in children. And he noticed that mechanical ventilation, central venous catheter, systemic infection, and prolonged hospitalization were risk factors. Dr. Sharath Kumar looked at 173 cases and 346 controls, also looked at all children, and saw a lot of the same risk factors there. Dr. Christy Atchison looked at 50 cases, 350 controls, and non-critically ill patients, and also found very similar risk factors there. The cool thing about this is even though it hasn't been externally validated, a lot of them looked at the same risk factors and found the same things. So this is where the CHAT consortium comes in, and CHAT stands for the Children's Hospital Acquired Thrombosis Consortium. So it's a consortium of 53 children's hospitals across the United States, and they really have three goals. The first of which is to perform these case control studies so that we can figure out which risk factors are the most important. The second thing is to derive risk assessment models for children and validate them in multiple centers around the US. And the third thing is to understand which subset of hospitalized children may benefit from thromboprophylaxis measures without that added bleeding risk. So looking at the risk assessment model for all hospitalized children, currently the case control has been done. They included over 800 VT cases and over 700 controls in eight children's hospitals across the US. And when you look at these risk factors, they're very similar to the ones that have already been noted in these single institution studies. So age, history of cancer, congenital heart disease, recent hospitalization, abraded mobility score, prior CVC placement surgery. The kind of neat thing to note is that they also included a platelet count in this risk assessment. And that's something that's used in the adults but not quite used in pediatrics yet. It's currently undergoing external validation at 24 hospitals. So hopefully in the next several months we will be able to know how good of a risk assessment model it is. The risk assessment model for critically ill children, specifically the children that we care for, has already been done. And they had 548 cases and 187 controls that are admitted or transferred to an ICU derived from eight CHAT centers. The main risk factors that they noted is abrading Q score less than two within 24 hours of ICU admission, length of stay greater than three days or equal to three days, central venous catheter place 30 days prior to or on ICU admission, congenital heart disease, and a past history of autoimmune inflammatory disorders or of course systemic infection. This now has been externally validated. This is new information as of the last few weeks. This was presented at ASH in December. And so in this recent study that's been externally validated, we had greater than 4,600 participants that were enrolled during this 30 month time span from three to consortium centers. And there was an incidence of 2.1% of hospital acquired BTEs equating to 93 events. And these are the results. So the initial risk assessment model derivation had an ROC of 0.79, following discrimination is 0.71. And after performing the Hosmer and Lemeshow goodness of fit test, showed that it was statistically significant with a P value less than 0.0001, which means that the expected and then the observed rate could not be explained by just chance alone. So pretty cool. So in summary, BTE leads to multiple acute and chronic sequelae in children. Hospital acquired BTE rates are continuing to increase and PICU patients and CICU patients are at high risk for developing a hospital acquired BTE. Studies before have attempted to do a risk assessment model and that the CHAT consortium is the first group to develop this multi-institutional risk model for all hospitalized children and critically ill children. These five high risk variables have been identified for critically ill children. We still need prospect of multi-center validation of the CHAT ICU. Oh, sorry. We've already done the multi-center validation of this risk assess model for ICU patients that result in good calibration discrimination. And that centers can consider implementing this in their local ICU. And we're hoping to do that in Denver as well. So these are all the centers involved in the CHAT ICU validation. And then I wanted to thank Dr. Jaffray. She couldn't be here today, but she did provide the slides and guidance for this. And then this is the whole CHAT team that's making this happen.

pediatric venous thromboembolism

central venous lines

CHAT consortium

risk assessment models

hospitalized children