Changes in Platelet, Granulocyte, and Complement Activation During Cardiopulmonary Bypass Using Heparin‐coated Equipment

Abstract

The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 +/- 632 ng/ml) and C4a (1088 +/- 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 +/- 1045 ng/ml and 1494 +/- 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 +/- 177 micrograms/L) and 10 min after the administration of protamine (676 +/- 314 micrograms/L) were significantly (p < 0.05) lower than in the other 2 groups (820 +/- 341 and 893 +/- 303 micrograms/L and 1365 +/- 595 and 1,258 +/- 622 micrograms/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma beta-thromboglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.

Relationship between granulocyte elastase and C3a under protamine dosing in on-pump cardiac surgery

“…Thus, they have concluded that granulocytes may be activated through complement activation [10]. They did not, however, directly examine the correlation between C3a and GEL concentrations at different time points after protamine administration.…”

“…The GEL concentration has been reported to be significantly lower in heparin-coated circuits, as compared to uncoated circuits [6,10,11]. The low level of GEL concentration at 60 min after CPB initiation is probably due to this inhibitory effect exerted by heparincoated circuits.…”

“…Fukutomi et al have demonstrated that a linear relationship between CPB time and C3a or GEL concentration existed, and that the C3a and GEL concentrations correlated during CPB [10]. Thus, they have concluded that granulocytes may be activated through complement activation [10].…”

“…However, the effect of protamine administration on granulocyte remains unknown [6]. In addition, few investigations have been conducted whether granulocytes could be activated by complement or not [6,10]. If granulocytes are activated through complement activation, GEL should increase significantly after protamine administration.…”

ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring

“…Most in vitro or animal models demonstrate benefits of heparin coating including reduced soluble thrombin production, platelet binding, and D-dimer production [12,[15][16][17][18][19]20]. With respect to inflammation, most studies demonstrate reduced inflammatory response, particularly in the interleukins, alternative complement pathway and polymorphonuclear cells, compared to controls and other coating systems [12,[20][21][22][23][24][25]26].…”