Clinicians should limit intraoperative blood transfusion during radical cystectomy, expert says

“Each unit of blood that you got during surgery was associated with about 7% higher odds of a VTE within 90 days,” says Timothy D. Lyon, MD, FACS.

In the following interview, Timothy D. Lyon, MD, FACS, discusses his recent Journal of Urology study1 that found an increased risk of venous thromboembolism following radical cystectomy when blood transfusion occurred intraoperatively. Lyon is a urologic oncologist at Mayo Clinic in Jacksonville, Florida.

Could you describe the background for this study?

Venous thromboembolism, and by that, I mean DVT, or deep vein thrombosis, and PE, or pulmonary embolism, is an important potential complication after cystectomy. We know it's pretty common; it happens somewhere between 5% and 8% of the time. It's very expensive; it's the most expensive index complication after radical cystectomy. It can be serious. In rare cases, it can be fatal. So, it's important for us to understand all the potential risk factors that may lead someone to develop a VTE, particularly if there's something that's modifiable that we could change.

We read with great interest a few papers that were published in the past few years in mixed surgical populations—so not in urology patients, but in patients undergoing multiple different types of surgery—that showed an association between blood transfusion and developing a VTE after surgery. We know there's a potential biologic rationale by which blood transfusion could lead to developing a VTE. We know red blood cells play a role in clot formation, and we also know that blood transfusion can induce inflammatory cytokines and might lead to a more prothrombotic state.

However, because those [studies] were [done with] administrative databases, they were limited by the inability to adjust for important confounders, specifically tumor stage, or how advanced the cancer was, as well as the use of preoperative chemotherapy. We know that both of those things are associated with the need for a blood transfusion and for developing a VTE. Our interest in this study was to see, was there a true association? Was there really a link between blood transfusion and VTE after we adjusted for those important features?

What were some of the notable findings? Were any of those surprising to you and your coauthors?

To look at this, we used the Mayo Clinic Cystectomy Registry. We identified a little over 3700 patients that had cystectomy between 1980 and 2020. Our primary outcome was a patient experiencing a VTE within 90 days of their surgery. After multivariable adjustment, we did find a significant association between blood transfusion and developing a VTE.

I think what was surprising to us is that when we specifically looked at timing, there did appear to be a unique time that was at a higher risk than others. We looked at transfusion as a 3-tiered variable. The first group had no transfusions. Group number 2 had an intraoperative transfusion—so [they] got a blood transfusion during surgery, and that included patients regardless of whether they needed one after surgery, so both with and without. The third group had only a postoperative transfusion—so not in the operating room, but only afterwards. When we looked at it this way, we found only the patients that had an intraoperative transfusion had a higher risk of VTE, not those that got it afterwards.

We then looked at it as a continuous variable. Each unit of blood that you got during surgery was associated with about 7% higher odds of a VTE within 90 days. That finding was robust to a number of sensitivity analyses. We looked at number of lymph nodes removed, operative time, we used an interaction term for year of surgery, along with blood transfusion. Despite all those adjustments, we still found the same significant result.

Is any further research on this topic planned? If so, what might that cover?

Our next step, and what I think is very important, is to try to validate or corroborate these findings in another dataset and see if we can observe the same phenomenon. If so, will have greater confidence that what we're observing is a true effect.

What is the take-home message for practicing urologists?

The take-home message is 2-fold. Number 1, we have seen that an intraoperative blood transfusion is associated with a higher risk of VTE afterwards. Clinicians should do whatever they're able to try to limit or reduce the need for an intraoperative transfusion. That would include measuring or assessing for anemia preoperatively and addressing it if possible using restrictive transfusion criteria in the operating room and other surgical maneuvers that might reduce the risk for needing a transfusion.

Postoperatively, I think physicians should be aware that those that got a transfusion in the OR are at high risk of having a VTE. We should have a low index of suspicion for assessing for that in our patients. We should remember that the use of prophylaxis is important. Sometimes we may be reluctant to use even low-dose blood thinners in patients that have had a recent blood transfusion, but we know these patients are at risk for developing clots, and wherever safe, we should strongly consider using these agents to reduce the risk.

Is there anything else that you would like to add?

It's important for clinicians that are doing radical cystectomy to strongly consider using extended duration VTE prophylaxis after surgery. We don't have any [randomized controlled clinical trials] (RCTs) in radical cystectomy specifically, but there are some RCTs in abdominal surgery more broadly that have shown a significant reduction in the risk of VTE for the use of extended duration or 28-day prophylaxis.

There was some elegant work recently published in the Journal of Urology by Dr. Mary Beth Westerman and some of her colleagues at MD Anderson2 that showed that an oral formulation with apixaban [made] patients more compliant with this, and they were more likely to take it compared with what had been studied previously, which was injections with enoxaparin. I think that's an acceptable and easy to use thing for patients, and I would strongly consider surgeons using this to reduce risk for their patients.

References

1. Myers A, Frank I, Shah PH, et al. Intraoperative blood transfusion is associated with an increased risk of venous thromboembolism after radical cystectomy. J Urol. Published online November 29, 2022. Accessed January 3, 2023. doi: 10.1097/JU.0000000000003094

2. Westerman ME, Bree KK, Msaouel P, et al. Apixaban vs Enoxaparin for pos-surgical extended-duration venous thromboembolic event prophylaxis: a prospective quality improvement study. J Urol. 2022;208(4):886-895 doi:10.1097/JU.0000000000002788