Hello, everyone. My name is Lauren Caldwell. I am currently a critical care pharmacist at Erlanger Health System in Chattanooga, Tennessee. And today, we'll be reviewing my research project, the comparison of factor products for uncontrolled bleeding related to cardiac surgery. Thank you. Neither I nor my co-investigators have anything to disclose. So the objective of our presentation would be to compare the efficacy and safety differences between low-dose recombinant factor VII and four-factor PCC in patients with bleeding related to cardiac surgery. So we defined low-dose recombinant factor VII within our study as less than 30 micrograms per kilogram. Just a little bit of background. So currently, recombinant factor VII and PCC have both been studied against the standard of care of allergenic blood products for bleeding for postoperative cardiac surgery patients. These agents have shown to reduce postoperative bleeding transfusion requirements as well as the need for reoperations. But what we don't know is the optimal dose and timing of these agents in regards to their surgery. So what we have are a limited direct comparison between these agents. And what we do have suggests that PCC has a lower thromboembolic risk when compared to recombinant factor VII. So this research was conducted at Erlanger Health System, which is an academic level one trauma center with a cardiothoracic surgery service that has a moderate annual volume of approximately 550 surgeries per year. And the purpose of our study was to determine if either recombinant factor VII or PCC requires less packed red blood cell transfusions within six hours of factor product administration. So our study was an IRB approved retrospective single center observational study that included patients who were at least 18 years of age, had thoracic surgery performed between 2017 and 2021, and received either of these agents either during or after surgery. We excluded patients who are pregnant, incarcerated, had congenital bleeding disorders, received ECMO during their admission, or refused blood products for any reason. So our primary outcome, again, was transfusion requirements of packed red blood cells within six hours of factor product. So additional secondary outcomes we reviewed were the transfusion requirements of any allergenic blood product, so packed red blood cells, platelets, and FFP, within 18 hours after surgery, additional doses of factor products if they were administered, hourly chest tube output, up to six hours pre and post administration, hospital length of stay, ICU length of stay, thrombotic events during their admission, the need for reoperation due to bleeding, as well as the development of AKI. So we screened 235 adult patients and included 179 patients. The primary reason for exclusion in our study was patients who received a higher dose of recombinant factor VII than 30 micrograms per kilogram. We performed statistical analysis using a CHI-squared or Fisher's exact for categorical data and Wilcoxon rank sum for continuous data. We also performed a logistic regression that included gender, weight, receipt of cell saver, surgery type, and DDAVP administration. So for our demographic data, primarily our patients in the PCC group were both male and of higher weight in comparison to recombinant factor VII. One thing we also wanted to account for was their pre-op antithrombotic use. So approximately 50% of patients in both groups were on mostly aspirin pre-surgery. As far as surgery type, most of our patients underwent an elective procedure with an open method that had similar cardiopulmonary bypass times, as well as the incidence of circulatory arrest during their procedure. For surgery type, most of our patients underwent an isolated CABG or valve-only procedure, and we included valve-only as either aortic or mitral valves, and then tricuspid valve and repairs went into the other category. As far as the doses that we utilized at our institution and that are included within our study, the initial dose of recombinant factor VII had a median dose of 14.9 micrograms per kilogram, or approximately 1,000 micrograms. So we do institute dose rounding within our institution. So pharmacists, upon order verification, are required to round to the nearest vial size to prevent waste and unnecessary cost to our patients. The PCC dose that we utilized in our study that we found was 6.4 units per kilogram, or roughly approximately one box of PCC, so 524 units. And both of these doses were administered at a similar time from surgery end, at approximately 160 minutes. So for our primary outcome of blood products administered within zero to six hours after factor dose, so approximately 70% of patients within both groups did receive packed red blood cells. However, though not statistically significant, there was a trend towards statistical significance with the volume of packed red blood cells that the PCC group received in comparison to the recombinant factor VII group. So as part of our secondary outcome, we looked at all blood products that were received between zero and 18 hours after factor products. So amongst packed red blood cells, FFP, and platelets, they were all similar between the groups and the amount received. However, when you look at terms of volume of these that were received, they were all statistically significant, and you can see that the patients in the PCC group all received an increase in the amount compared to their recombinant factor VII group. So we also looked at the additional doses of factor products that patients received. In the PCC group, there was almost 50% of patients who required a second dose of these agents, with 22% of them receiving additional dose of PCC and 33% of them receiving a dose of recombinant factor VII. It's important to note that within our study, patients could receive an additional dose of an additional factor product, or could cross over and receive recombinant factor VII, or potentially receive both agents as a second and third dose. So when you look at this additional doses of PCC that was received between both groups, it was about one box, again, at 500 units. And then if you look at the additional doses of recombinant factor VII, they are higher than what our initial median dose was of patients received, so they're 1,500 micrograms versus 1,350 micrograms in comparison to our previous median dose that we saw was 1,000 micrograms. In terms of additional secondary outcomes, the reoperation due to bleeding was not statistically different between our cohorts. We also wanted to look at thrombotic events. This is something that has been previously reported in the literature with these agents. So what we found was there was no difference between the two groups of our patients who developed a thrombotic event, and we broke it down to see if either of these patients had multiple doses of these agents and only one patient within the PCC group had developed a thrombotic event and had received multiple doses of factor products. In terms of ICU length of stay, hospital length of stay, and in-hospital mortality, they were all higher within the PCC group. However, we're really unable to draw strong conclusions from this due to the limited number of patients within our study, and our in-hospital mortality is in line with previous literature. So test-tube output is something that if you read other previous studies that have looked at these agents was one of their primary outcomes, so we also wanted to evaluate this. So we looked at test-tube output six hours pre- and post-factor product, and they were not statistically different between both groups. We're not able to collect all of the patients from the PCC group due to intraoperative administration of some of those because we store PCC within our OR anesthesia cabinets. However, recombinant factor VII comes from the pharmacy, so they have easy access to this. And so that's why we're unable to collect all of their data because the anesthesia records do not account for test-tube output. So renal morbidity is something that's also been previously reported in the literature with factor products in this patient population, and we found that the PCC group was about 50% more likely to develop an AKI when compared to recombinant factor VII. We defined AKI within our study based on the RIFLE criteria, as this is what is cited or utilized for the Society of Thoracic Surgery's metrics. And we found that the PCC group was more likely to progress to renal failure in comparison to the recombinant factor VII group. We tried to account for some of the confounders with this with the use of nephrotoxic agents. So we collected contrast dyes, NSAIDs, immunoglycosides, and multiple doses of vancomycin. However, we were unable to account for all the potential causes of AKI, so hypotension, prolonged bypass time, blood loss, anemia, those types of things. We tried to account for as many things as we could. For limitations of our study, it is a retrospective single-center study over five years, and our institution does have a lack of a standard bleeding algorithm. We do have the same small group of providers that do care for these patients, and they care for them in similar manners. However, there's not a bleeding algorithm that's instituted at our facility. There was crossover between our groups from their initial dose and the secondary dose for refractory bleeding. So 7.7% of patients who initially received recombinant factor VII did get a PCC dose, and 33% of patients who initially received PCC did get a dose of recombinant factor VII. And the doses that we utilized in our study were found to be lower than PROS has previously been reported, and we don't know what this effect has on our hemostatic results. So in conclusion, we did not find any difference in our primary outcome of PACT-RED blood cell administration, and the doses of additional factor products as well as more blood products that were administered during the zero to 18-hour window potentially suggest that a lower doses of PCC may have decreased efficacy compared to recombinant factor VII, and additional studies are warranted to determine the optimal approach as well as timing of these agents. I'd like to thank my team for their help with my research, and I will now take any questions you guys may have.

efficacy

safety

uncontrolled bleeding

factor products

cardiac surgery