Heparin-coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin-2 of the lectin complement pathway in vivo

Abstract

SummaryThe complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands, including biomaterials in vitro, and low ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, −2 and −3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3-mediated complement activation potential was evaluated with C4, C3 and TCC as output. There was no significant difference between the two circuit materials regarding MBL, ficolin-1 and −3. In the Bioline® group the ficolin-2 levels decreased significantly after initiation of surgery (P < 0·0001) and remained reduced throughout the sampling period. This was not seen for Phisio®-coated circuits. Ficolin-3-mediated complement activation potential was reduced significantly in both groups after start of operation (P < 0·0001), whereas soluble C3a and TCC in the samples were increased (P < 0·0001). Ficolin-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures.

Ficolin-2 inhibitors are present in sera after prolonged storage at −80 °C

“…We and others have reported the specific inhibition of ficolin-2 by the coating in plastic serum collection tubes (Brady et al, 2014c; Hein et al, 2013), and others have observed the depletion of ficolin-2 by heparin-treated cardio bypass circuits (Hein et al, 2015). Ficolin-2 was observed to bind to derivatized Sepharose (Kilpatrick & Chalmers, 2012), and commercial complement component-depleted sera are deplete of ficolin-2 as well (Brady et al, 2014b).…”

Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery

“…More recently, Hein et al . demonstrated lectin pathway activation during cardiopulmonary bypass by measuring the residual capacity for complement activation mediated by MBL and ficolins which was parallel to the increase of C3a. The phenomenon was observed independently of the oxygenator/circuit type (heparin‐ or physio‐coated).…”

“…Then Billgin et al [13] suggested that fresh frozen plasma transfusion to MBL-deficient patients led to the development of postoperative sterile SIRS. More recently, Hein et al [25] demonstrated lectin pathway activation during cardiopulmonary bypass by measuring the residual capacity for complement activation mediated by MBL and ficolins which was parallel to the increase of C3a. The phenomenon was observed independently of the oxygenator/circuit type (heparin-or physio-coated).…”

The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

“…Studies on CPB have shown us that the use of centrifugal pumps, now ubiquitous in modern ECMO, reduces complement activation [82, 83]. In addition, the use of contemporary heparin-bonded circuits has also been shown to reduce complement activation [84]. Studies have examined complement activation in ex-vivo models of ECMO [20, 22, 24], neonatal ECMO [20, 23, 25] and in adult patients [21].…”