The use of prothrombin complex concentrate as a warfarin reversal agent in pediatric patients undergoing orthotopic heart transplantation

Abstract

Background Patients supported with a ventricular assist device are predisposed to severe bleeding at the time of orthotopic heart transplant due to several risk factors including anticoagulation with vitamin K antagonists. Kcentra, a four‐factor prothrombin complex concentrate, has been approved by the FDA for warfarin reversal in adults prior to urgent surgery. There is a lack of published data on the preoperative use of four‐factor prothrombin complex concentrates in pediatric patients undergoing cardiacsurgery. Methods This is a single‐center retrospective analysis of pediatric patients with a continuous‐flow ventricular assist device who underwent heart transplant, comparing patients who received Kcentra for anticoagulation reversal with a historical patient cohort who did not. Consecutive patients from January 2013 to December 2017 were analyzed. The primary outcome was volume of blood product transfusion prior to cardiopulmonary bypass initiation. Secondary outcomes include blood product transfusion after cardiopulmonary bypass intraoperatively and up to 24 hours postoperatively, chest tube output within 24 hours of surgery, time to extubation, incidence of thromboembolism, and post‐transplant length ofstay. Results From 2013 to 2017, 31 patients with continuous‐flow ventricular assist devices underwent heart transplant, with 27 patients included in the analysis. Fifteen patients received Kcentra compared with 12 patients who received fresh‐frozen plasma for anticoagulation reversal. Compared with the control group, patients who received Kcentra had less packed red blood cells, fresh‐frozen plasma, and platelets transfused prior to cardiopulmonary bypass initiation. The Kcentra group also received less packed red blood cells on bypass and less packed red blood cells after cardiopulmonary bypass termination. There were no differences in chest tube output, time to extubation, intensive care unit length of stay, or overall hospital length of stay. Neither group had thromboembolic complications detected during the first seven postoperative days. Conclusion This small retrospective study indicates that preoperative warfarin reversal with Kcentra reduces blood product exposure in pediatric patients with ventricular assist devices undergoing heart transplant.

Overview of Plasma and Platelet Transfusions in Critically Ill Children

“…Refaai et al compared the use of prothrombin complex concentrates (PCC) with the use of FFP for anticoagulant reversal in adults and found that plasma was independently associated with volume overload (18). In addition, a small single center retrospective study by Sisti et al found that the use of PCC in pediatric patients with ventricular assist devices, for anticoagulation reversal prior to heart transplant, limited their exposure to exogenous blood products (19). Additional studies are needed to determine the best situation for each product in the pediatric population.…”

Evaluation of the Safety and Efficacy of a Novel Thrombin Containing Combination Hemostatic Powder Using a Historical Control

“…Postoperative bleeding following cardiothoracic procedures remains an important concern with multiple avenues of investigation continuing to assess factors predisposing and potentially influencing the severity of this adverse event. Recent areas of interest include: development of new antifibrinolytic agents to reduce bleeding; 31 measurement of platelet function to reduce bleeding and mortality; 32 single or dual agent antiplatelet therapy to maximize bypass graft patency, but increase postoperative bleeding; 33 – 36 direct linkage of postoperative cardiac surgical bleeding with increased cost; 4 , 5 safe and efficacious use of postoperative fibrinogen concentrates; 37 , 38 role of patient blood management in reducing blood product transfusion and improving cardiac surgical outcomes; 39 , 40 transfusion reductions associated with the use of prothrombin complex concentrate; 41 , 42 morbidity associated with reoperation for bleeding following cardiac surgery; 3 , 43 , 44 methods of employing thromboelastometry (ROTEM) during cardiac surgery; 45 , 46 contribution of albumin/gelatin to postoperative bleeding; 47 – 49 advantages of anticoagulation management using thromboelastography (TEG) during cardiopulmonary bypass; 50 – 52 benefit of thrombin inhibitors for pediatric VAD anticoagulation; 53 , 54 reduction of postoperative blood loss using Unilastin as an antifibrinolytic agent; 55 , 56 and blood loss leading to multisystem organ failure and hematologic complications following LVAD insertion. 7 , 57 …”

Prothrombin Complex Concentrate Utilization in Children's Hospitals

“…2 Recent reports describe that in ventricular assist device-dependent pediatric patients requiring VKA reversal prior to heart transplantation, PCC receipt use was associated with decreased blood product transfusion (PRBCs, FFP, and platelets) compared with FFP. 13 Understanding rapid repletion of coagulation factors following CPB is essential for optimizing outcomes, we were not surprised to find an increasing rate of PCC utilization. However, it is important to note that data to support PCC use in pediatric cardiovascular procedures are limited to small case series in both pretransplant VKA reversal 13 and post-CPB hemorrhage.…”

“…13 Understanding rapid repletion of coagulation factors following CPB is essential for optimizing outcomes, we were not surprised to find an increasing rate of PCC utilization. However, it is important to note that data to support PCC use in pediatric cardiovascular procedures are limited to small case series in both pretransplant VKA reversal 13 and post-CPB hemorrhage. 14 In post-CPB hemorrhage, there are no prospective data to support routine or prophylactic PCC use, and such use should be approached with caution.…”