Does heparin pretreatment affect the haemostatic system during and after cardiopulmonary bypass?

In this clinical pilot study, the influence of heparin pretreatment on the haemostatic system during and after cardiopulmonary bypass (CPB) was investigated. Thirteen patients scheduled for elective coronary artery bypass grafting (CABG) were divided into two groups: heparin pretreated (HP, n = 6) and non-heparin pretreated (NHP, n = 7). Blood samples were taken for measurements of plasma antithrombin-III (AT-III) activity, plasma heparin levels, activated clotting time with (HACT) and without (ACT) heparinase, whole blood platelet function, platelet count, thrombin-antithrombin-III complexes and D-dimer levels. Also, the mediastinal blood loss within the initial 20 h after surgery, and the blood transfusion requirements were monitored. The mean duration of the heparin pretreatment was 55 h (range 24-161 h). There was no significant difference in plasma AT-III activity and platelet count between the groups. Before and after CPB, the platelet responsiveness was better in the NHP group (p < 0.05). The HACT was prolonged in the NHP group during and after CPB compared to baseline values (p < 0.05), whereas, in the HP group, no significant changes were found. Plasma heparin levels and ACT values suggested adequate anticoagulation during CPB. However, the extent of thrombin inhibition and fibrinolysis increased with time on CPB, but did not differ between the two groups. Twenty hours after surgery, the thrombin inhibition showed to be significantly higher in the NHP group. Furthermore, mediastinal blood loss showed a tendency to be lower in the HP group (p = 0.08). However, there was no difference in blood transfusion requirements between the groups. These data suggest that short-term heparin pretreatment affects the perioperative platelet responsiveness and attenuates the consumption of coagulation factors.

Familial antithrombin-III deficiency during cardiopulmonary bypass: a case report.

The serine protease inhibitor antithrombin-III (AT-III) is the principal in vivo inhibitor of blood coagulation, inactivating mainly thrombin, but also other serine proteases. Binding of AT-III to heparin dramatically increases its inhibitory effect. AT-III deficiency during cardiopulmonary bypass (CPB) can lead to insufficient anticoagulation which cannot be treated by higher doses of heparin. A 60-year-old male with familial AT-III deficiency was admitted to our hospital for coronary artery bypass surgery and aortic valve replacement. Four days before the operation, acenocoumarol was stopped and anti-Xa nadroparincalcium (Fraxiparine) was started. AT-III activity at that time was 56%. Two hours before the operation, a single dose of 4500 IU AT-III concentrate was administered. Heparinization was performed with 400 IU/kg of porcine mucosal heparin, increasing the activated coagulation time (ACT) from a baseline of 115 to 549 s. AT-III activity at that time was above 100% and the plasma D-dimer concentration was 230 ng/l. ACTs during CPB remained above 999 s, whereas the AT-III activity dropped to 54% and the D-dimer increased up to 500 ng/l at the end of CPB. CPB was terminated uneventfully. Heparin was reversed with 3 mg/kg protamine chloride, decreasing the ACT to 155 s. In the intensive care unit (ICU), the patientreceived prophylactic Fraxiparine and 1500 IU AT-III, increasing the AT-III activity to 84%. Postoperatively, there was continued blood loss, which necessitated the administration of whole blood and eventually re-exploration. The case presented illustrates an uneventful treatment of a patient with a hereditary AT-III deficiency undergoing CPB. In spite of an uneventful treatment with AT-III pre-CPB, administration of prophylactic AT-III concentrate after surgery should be considered with caution, as this might increase the postoperative morbidity.