In vitro effect of hemodilution on activated clotting time and high-dose thrombin time during cardiopulmonary bypass

Extreme dilution of clotting factors, as may occur during pediatric or neonatal cardiopulmonary bypass, often leads to inadequate monitoring of anticoagulation with activated clotting time (ACT). In this study we postulate that the high-dose thrombin time (HiTT) is less influenced by extreme dilution of clotting factors because it stimulates clotting through the common pathway.

Heparinized prebypass blood was obtained from 30 adult cardiac surgical patients and was diluted in a laboratory setting with saline solution to mimic the clinical clear prime solution (group I; n = 10), with saline solution containing similar heparin as in the prebypass blood (group II; n = 10), and with fresh frozen plasma to substitute clotting factors in the diluted blood (group III; n = 10). Blood was diluted to four different degrees: a control without dilution, 25%, 50%, and 75% dilution. The ACT and HiTT were measured and compared.

In group I, significant prolongation of ACT was observed in blood diluted to 75% as compared with the nondiluted blood (p < 0.01). In contrast, HiTT was not prolonged at any degree of dilution but reduced proportionally to dilution up to 75%, reflecting the concomitant reduction of heparin. In group II, ACT increased at 25% dilution (p < 0.01) whereas HiTT increased at 50% dilution (p < 0.01). In group III, no prolongation of ACT or HiTT was found in any degree of dilution. Furthermore, adding fibrinogen to the diluted blood (n = 4) did not cause ACT to recover at 75% dilution, suggesting that dilution of other factors in the early clotting cascade rather than fibrinogen alone increases ACT.

These results imply that when blood is extremely diluted during cardiopulmonary bypass with a clear prime without substituted clotting factors, HiTT is a better test than ACT for anticoagulation monitoring.