Thrombin generation in on-pump cardiac surgery patients

Objective

Cardiac surgery, in particular when done with cardiopulmonary bypass (CPB), is frequently associated with excessive intraoperative and postoperative bleeding. Here we employed the Technothrombin^® thrombin generation assay (TGA; Technoclone) to monitor changes in perioperative haemostasis.

Methods

One hundred and forty-eight patients (age 66.0 ± 9.8 years; 103 males, 45 females) with elective cardiac surgery and a CPB time >45 minutes (mean 114 ± 56 min) were enrolled. Arterial blood samples were obtained preoperative, postoperative and 14–18 hours postoperative and centrifuged within 30 minutes after withdrawal, for 5 minutes at 5,000 × g. Plasma samples were stored until analysis at -80°C. Thrombin generation (TG) induced by the TGA RC low reagent (71.6 pM tissue factor) was measured in 96-well multiplates using a FLUOstar OPTIMA fluorescence reader (MWG Labtech).

Results

Due to cardiac surgery, the lag-phase and time-to-peak of TG increased by 45% and 35%, respectively. In parallel, the peak thrombin concentration and maximum slope decreased by 42% and 51%, respectively (P < 0.000001). Both the lag-phase and time-to-peak returned to basal values within 14–18 hours postoperative, but the peak thrombin and maximum slope of TG rose above the preoperative values (+39% and +68%, P < 0.0005). The on-pump time was positively correlated with lag phase and time to peak and negatively correlated with peak thrombin and maximum slope of TG when measured at 14–18 hours postoperative, but there was no correlation at early postoperative. With respect to classical coagulation parameters, significant correlations were observed between TG and activated partial thromboplastin time at preoperative and 14–18 hours postoperative, and between TG and prothrombin time at postoperative (P < 0.025–0.001). At 14–18 hours postoperative there was a significant correlation of TG with platelet as well as leukocyte counts (P < 0.025).

Conclusion

The data provide clear evidence for a marked decrease of TG during cardiac surgery followed by an excess restoration in the postoperative phase. Factors released from platelets and leukocytes (procoagulant microvesicles?) might contribute to the enhanced TG observed at 14–18 hours postoperative.