INTRODUCTION

Prothrombin complex concentrate use (PCC) may be complicated by thrombosis, and increased factor II levels are recognized as a risk factor.1 When administering PCCs in cardiac surgery patients using K Centra ®, a 4-factor PCC for warfarin reversal, or Profilnine®, a 3-factor PCC for refractory hemorrhage, we administer a low-dose of 1000-2000 units and initially measured post-dose factor II activity, for quality control. These QC findings were the basis for a hematology/anesthesiology/surgery based standardized, refractory bleeding algorithm (Figure 1). However, the risk of thromboembolic events in this patient population is not well characterized. Therefore, we evaluated our patient population for perioperative thromboembolic events.

METHODS

A retrospective review of 85 patients (11 presented here, 85 to be presented in December) from January 2014 to April 2015 who activated the refractory bleeding algorithm were examined. Data include demographics, comorbidities, lab values, blood product usage, PCC and rFVIIa doses, chest tube output and postoperative thromboembolic complications i.e. (cerebral vascular accidents, myocardial infarction, pulmonary embolism or deep vein thrombosis.) Descriptive statistics: percentage, mean +/- standard deviation (SD) or median [interquartile range (IQR)] will be used to describe the results.

RESULTS

Initially, from March 2014 to October 2014, 11 complex cardiothoracic surgery patients received PCCs. Average age was 59(+/-14) years and 2/11(18%) died. Patients received 28 (+/-21) units per kilogram ideal body weight PCCs (K Centra 27 (+/-22), Profilnine 24 (+/-20)). The average, post-dose factor II levels were 78 (+/-16)%; 3/11 (27%) patients were below our normal reference range (72-132%), even after dosing, and two received a third dose. One patient died 3 days after a heart transplant and KCentra administration that was complicated by cardiogenic shock requiring biventricular mechanical support with late thrombosis, in the setting of blood stagnanattion and inability to anticoagulate due to poor BiVAD flows and continued (surgical) bleeding respectively.

DISCUSSION

Our initial findings from this on-going safety evaluation of our institutional adoption of a factor concentrate based, refractory bleeding algorithm represent an important therapeutic approach to major bleeding in a cardiac surgical setting where major bleeding is common. We noted a single episode of catastrophic thrombosis likely due to technical difficulties as post-dose INR was 1.6 and factor II activity was low at 60% (normal 72-132%), supportting a primary stasis/mechanical etiology. While (7/11) patients had a significant reduction in bleeding severity, 4/11 had ongoing hemorrhage requiring additional blood products (3/4) and rFVIIa (2/4). Low-dose PCCs barely normalize the FII activity levels and additional therapies were needed for 4/11 patients, presenting possible benefit from increased dose or repeated low-dose protocols. These preliminary data illustrate the need for careful evaluation of the results of algorithm implementation. Treatment failure may support the use of other procoagulant products such as FEIBA, if rFVIIa is required in addition to PCC for life threatening hemorrhage. Our presentation will include follow-up for thromboembolic events, blood product utilization, treatment failure rates and laboratory values for all 85 patients.

Disclosures

Off Label Use: Prothrombin complex concentrates and rFVIIa use in the perioperative/surgical and intensive care settings.. Ortel:Daiichi Sankyo: Consultancy; Instrumentation Laboratory: Consultancy; Instrumentation Laboratory: Research Funding; Eisai: Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.