Preemptive intraoperative administration of PCC4 in cardiac surgery patients at high risk of bleeding, a pilot study
Authors: Elder Joseph , McComb Jennifer , Lirette Seth , Herndon Bruce , Yancey Gerald , Mohammed Asim , Copeland Hannah 
Published: September 2022

Background: Four factor prothrombin complex (PCC4), a concentrate of
factors II, VII, IX, X and protein C and S, has been used selectively
for reversal of oral anticoagulation prior to surgery.  There is data to
support PCC4 as opposed to supplemental fresh frozen plasma (FFP) to
manage postoperative bleeding following cardiac surgery.  The
preemptive, intraoperative use of PCC4 in cardiothoracic surgery has not
been studied though it may prevent postoperative bleeding, the need for
blood transfusion and the risk of transfusion related acute lung injury,
volume overload, and right ventricular (RV) heart failure. The purpose
of this study is to evaluate the intraoperative administration of PCC4
to decrease bleeding and lower the rate of blood transfusion. Methods: A
single institution retrospective chart review conducted from May 2020 to
November 2021 of patients who received PCC4 intraoperatively during
cardiothoracic surgery of high risk variety. Patients were evaluated for
type of surgery, demographics, baseline anticoagulation, PCC4 dose, type
and quantity of blood transfusion within 72 hours postoperatively, chest
tube output, incidence of right ventricular failure, hypersensitivity
reactions, acute kidney injury, thrombosis, acute lung injury, and
mortality within 45 days of the operative dose of PCC4. Results: Thirty
five patients received PCC4 at a mean dose of 2920 units. Sixty five
percent of cases were LVAD or heart transplant. The protocol is to use
PCC4 30 units/kilogram immediately after completion of protamine
administration. Inclusion criteria are: cardiothoracic surgery with
increased risk of postoperative right heart failure commonly secondary
to blood product transfusion, or cardiothoracic surgery associated with
increased risk of bleeding, including: heart transplant, LVAD implant,
aortic dissection, and redo sternotomy (e.g. coronary artery bypass).
Total chest tube output was recorded as a mean of 757 mL for 24 hours
after surgery (32 ml/hr). Overall median event rates of fresh frozen
plasma (FFP) and red blood cell (RBC) transfusion were 0 (interquartile
range 0 - 3 units) and 4 (interquartile range 2-5 units). Overall,
forty-three percent and eighty-nine percent of cases received FFP and
RBC, respectively.  There was one occurrence of right ventricular
failure, one occurrence of acute kidney injury requiring renal
replacement therapy, one occurrence of venoarterial extracorporeal
membrane oxygenation, one occurrence of venous thromboembolism related
to a central venous access line, and one death unrelated to surgery or
PCC4 that was attributed to advanced heart failure not amenable to
advanced therapies. Conclusion: Overall patients received a low rate of
blood transfusion, had minimal chest tube output, and there was a small
incidence of right heart failure. Patients did not have an increased
risk of adverse effects such as acute kidney injury or venous
thromboembolism. A randomized controlled clinical trial comparing the
observed dose and timing of PCC4 versus routine postoperative bleeding
management with blood product transfusion is recommended.