Heparin Dose and Point-of-Care Measurements of Hemostasis in Cardiac Surgery—Results of a Randomized Controlled Trial

Abstract

Objective: High heparin doses during cardiopulmonary bypass (CPB) have been suggested to reduce thrombin activation and consumption coagulopathy and consequently bleeding complications. The authors investigated the effect of a high heparin dose during CPB on point-of-care measurements of coagulation. The authors hypothesized that during CPB a high heparin dose compared with a lower heparin dose would reduce thrombin generation and platelet activation and tested whether this would be reflected in the results of rotational thromboelastometry (TEM) and platelet aggregation, measured with multiple electrode aggregometry (MEA). Design: Prospective, randomized, controlled, open single-center study. Setting: University teaching hospital. Participants: Sixty-three consecutive patients undergoing elective coronary artery bypass grafting with CPB were enrolled. Interventions: Patients were randomly assigned to receive either a high (600 IU/kg, n = 32) or a low (300 IU/kg, n = 31) initial dose of heparin. Target levels of activated clotting time during CPB were >600 seconds in the high heparin dose group and >400 seconds in the low heparin dose group. Measurements and Main Results: Blood samples were collected (1) preoperatively after induction of anesthesia, (2) 10 minutes after aortic declamping, (3) 30 minutes after protamine administration, and (4) 3 hours after protamine administration. TEM and MEA were then measured. There was no difference in blood loss up to 18 hours postoperatively (median 735 mL for high dose v 610 mL for low dose; p < 0.056) or transfusions between the groups. Total median heparin dose (54,300 IU v 27,000 IU; p = 0.001) and median antifactor Xa levels during CPB (9.38 U/mL v 5.04 U/mL; p = 0.001) were greater in the high than in the low heparin dose group. However, neither TEM nor MEA results differed significantly between the groups. Conclusions: Compared with a lower dose of heparin during CPB, a high dose of heparin had little effect on the point-of-care measurements of hemostasis, TEM, and MEA. Based on the similarity of platelet and coagulation activity assessments, the higher heparin dose does not appear to offer benefit during CPB.

Modifiable Risk Factors associated with Post-Operative Bleeding and transfusion requirements in Cardiac Surgery

“…24,25 Recently reported studies stated that monitoring of platelet function are feasible and beneficial during and after CPB. [26][27][28] ADP activation test might be useful to determine the CPB effect on platelet function. 29 Assessment of preoperative platelet function would result in decrease frequency of postoperative bleeding and blood transfusion as compared to those of the postoperative evaluation.…”

Point-of-Care Platelet Function Monitoring: Implications for Patients With Platelet Inhibitors in Cardiac Surgery

“…However, recent studies suggested platelet function monitoring to be partially feasible and useful during and after CPB. 64,68,82,85,86 Platelet activation via the thrombin receptor seems quite robust. In contrast, the ADP receptor is thought to be most sensitive to CPB-induced alteration, with restoration of platelet function after 24 hours to near-normal values.…”

“…These findings suggeststhat platelet reactivity becomes depressed during CPB but seems to quickly recover thereafter. 64,68,82,85,86 Within different test assays, it seems that tests evaluating the thrombin-receptor pathway are most suitable to monitor basal platelet function and could be used as a reference. Effects of CPB on platelet function might be best estimated and monitored using ADP activation.…”

Toward Optimal Anticoagulation Monitoring During Cardiopulmonary Bypass: It Is Still A Tough “ACT”

“…It seems rather unrealistic to find clinically relevant outcome differences between ACT devices, due to existing variability in heparin products, heparin dosing schemes, and CPB circuits. 5,6,14,15 Alternatives to conventional ACT measurements have been suggested. Results from heparin-protamine titration system, (also called heparin monitoring systems) might better reflect the real heparin activity than common ACT devices.…”

“…In summary, heparin remains the drug of choice for mandatory anticoagulation during CPB, but optimal dosing to achieve best patient outcomes is unclear. 1, 15 Similarly, ACT has a long track record as the preferred monitoring system of heparin activity during CBP despite the lack of strong evidence or optimal targets in relation to clinical outcomes. It is supposed that ACT will remain the most common assessment of adequate heparin effects during CPB in the near future.…”