High and low heparin dose with heparin-coated cardiopulmonary bypass: activation of complement and granulocytes

Cardiopulmonary bypass with heparin-coated circuits allows reduced amounts of systemic heparin. Heparin inhibits activation of the complement cascade experimentally, but the effects of different levels of systemic heparin on activation of complement and granulocytes in patients have remained unknown.

Fifty-two patients undergoing coronary artery bypass procedures were studied. Cardiopulmonary bypass circuits completely coated with surface-bound heparin were used for one group given low-dose heparin (n = 17) (activated clotting time > 250 seconds), and was compared with a second group having normal high-dose heparin (activated clotting time > 480 seconds) (n = 18). A third control group was perfused with ordinary uncoated circuits and a full heparin dose (n = 17).

During cardiopulmonary bypass, the C3 activation products C3b, iC3b, and C3c increased markedly in all three groups compared with baseline, but significantly less in the two heparin-coated groups (high dose, median maximal increase 58 arbitrary units (AU)/mL; low dose, 48 AU/mL) compared with the uncoated control group (74 AU/mL) (p < 0.01). The difference between the two coated groups was not significant. Similarly, the maximal increase in terminal SC5b-9 complement complex was considerably lower in the heparin-coated groups (high dose, 2.5 AU/mL; low dose, 2.6 AU/mL) compared with the level observed in the uncoated control group (5.3 AU/mL) (p < 0.01). The release of the granulocyte activation enzymes myeloperoxidase and lactoferrin increased from the beginning of the operation, with peak levels at the end of cardiopulmonary bypass (p < 0.01). The concentration of lactoferrin was significantly (p < 0.01) reduced in the low heparin dose group compared with the two other groups receiving normal high heparin doses, indicating that circulating heparin is an important granulocyte agonist, acting independently of the presence or absence of heparin-coated surfaces. Also for myeloperoxidase a higher level was observed in the high heparin dose group.

Complement activation was significantly reduced in both heparin-coated groups and was independent of the level of systemic heparinization, whereas granulocyte activation was reduced only in patients who received low doses of systemically administered heparin. The results indicate that a moderate reduction of the systemic heparin dose may be an advantage with regard to improved biocompatibility when using heparin-coated cardiopulmonary bypass circuits.