The use of post-bypass four-factor prothrombin complex concentrate (PCC) decreases transfusions of both red blood cells and plasma in patients undergoing an orthotopic heart transplant who have existing left ventricular assist devices (LVADs), a study has found. The use of the agent, however, did not result in shorter lengths of stay (LOS) in the ICU or hospital, and was not associated with thrombotic complications.
“We see a large number of patients who are undergoing heart transplants with LVADs,” said Grace S. Kao, MD, associate professor of medicine at Tufts University School of Medicine, in Boston, “and we’ve noted that surgeries in these patients are much bloodier than in patients undergoing transplant alone. They also tend to use more blood products, which can have long-term side effects, as well as short-term infusion reactions. Therefore, we wanted to know if we can somehow improve the quality of these surgeries and patient outcomes by incorporating four-factor prothrombin complex concentrate.”
An Expensive Drug
Dr. Kao and her colleagues identified 73 consecutive patients who underwent an orthotopic heart transplant with LVAD between May 2013 and September 2016. Of these patients, 32 received four-factor PCC (Kcentra, CSL Behring) concomitantly with protamine administration and 41 did not.
The groups were similar with regard to age, sex, body mass index, preoperative lab findings, duration of cardiopulmonary bypass and number of prior sternotomies. The researchers evaluated many end points, including blood product utilization, ICU and overall hospital LOS, and thrombotic complications.
“The other question is how to use this drug properly,” Dr. Kao said in an interview with Anesthesiology News. “Its indication is really in patients on warfarin who are bleeding and need to be reversed acutely. People don’t often use it in scheduled surgeries because it’s so expensive. So by using this concentrated drug, are we improving the outcomes of these patients, even though we’re not saving money?”
As Dr. Kao reported at the 2017 annual meeting of the Society of Cardiovascular Anesthesiologists (abstract SCA97), a median of 2,500 units of four-factor PCC (range, 2,000-3,000 units) was given to each patient. The analysis also revealed that patients who received the study drug had significantly fewer median red blood cell units transfused (2.0; interquartile range [IQR], 1.0-2.5) than those who did not (5.0; IQR, 3.0-7.0; P<0.001). The median units of plasma transfused were also less, at 1.3 (IQR, 0-2.0) in the study group, compared with 6.0 (IQR, 4.0-8.0) for those who did not receive four-factor PCC (P<0.001).
After controlling for preoperative hematocrit, preoperative international normalized ratio and duration of cardiopulmonary bypass, multivariate regression analysis also showed that patients who received the study drug required fewer red blood cells and plasma units (P<0.001). Despite these differences, postoperative ICU and total hospital LOS were similar between groups.
As Dr. Kao discussed, no thrombotic complications occurred in either group, a finding that may have come as a pleasant surprise. “The drug can also cause side effects for patients undergoing surgery; it may put them at higher risk of having clots,” she said. This can cause deep vein thrombosis, pulmonary embolism or microvascular clots that can harm kidney function.
Although these agents are expensive, Dr. Kao thought they were a worthwhile investment under the right circumstances. “We use it, especially in patients who are on warfarin and are already anticoagulated.”
The trial may also have revealed some unexpected benefits of using four-factor PCC. “It definitely seems like we are finishing the surgery a lot faster,” she said. “The surgeons have also commented that the field is not as bloody and doesn’t have to be cleaned as much during the surgery. And that may impact how comfortable the surgeon is when doing the surgery.
“Does that have any effect on morbidity or complications? We don’t know. We’ll need more patients before we can evaluate these kinds of results,” Dr. Kao noted. The trial continues to enroll patients.
According to Laurie K. Davies, MD, associate professor of anesthesiology and associate professor of surgery at the University of Florida College of Medicine, in Gainesville, the examination of four-factor PCC is an important area of research, and one that demands prospective analysis of risk and benefit. “A retrospective review is tantalizing, but it is hard to make conclusions based solely on pilot work.”
Dr. Davies raised questions about the study, including the determination of which patients received the study drug and the dose, transfusion triggers and discharge criteria, but she thought the findings had potential for clinical practice.
“We also have some experience using PCCs in patients undergoing cardiac surgery,” she said. “The issue we are always facing is how to balance the clear efficacy of these drugs in promoting hemostasis while avoiding the complications of excess clotting. I was gratified to read that the authors did not see any complications secondary to thrombosis. I also was quite impressed with the decrease in blood product exposure. As we know, transfusion has its own set of complications.”