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

https://doi.org/10.1053/j.jvca.2019.12.050Get rights and content

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.

Section snippets

Patients

Sixty-three consecutive patients undergoing elective CABG with CPB were enrolled into this prospective, randomized, controlled, single-center study between February 3, 2012, and March 11, 2015. The Ethics Committee of the Hospital District of Helsinki and Uusimaa, Helsinki, Finland, approved the study. All patients gave written informed consent to participate in the study. Exclusion criteria were as follows: urgent surgery; redo surgery; concomitant cardiac surgery in addition to CABG;

Study Population

The patient characteristics were comparable between the study groups (Table 1). There were no differences in comorbidities, medications, or preoperative laboratory values between the study groups (data not shown). No major adverse events (eg, stroke, myocardial infarction, venous thromboembolism, acute kidney injury or resternotomy) occurred during the study. The surgical data are presented in Table 2.

Heparin and Protamine Dose

Total heparin dose (median 54,300 [IQR 46,950-62,250] IU v median 27,000 [IQR 24,420-34,920]

Discussion

In patients who received either a high or a conventional dose of heparin during CPB, there were no significant dose-dependent differences in TEM ExTEM CT, ExTEM MCF, or FibTEM MCF values, except for a small difference in ExTEM CT at 3 hours after protamine administration. Strikingly, all of the median TEM values studied in citrated blood were within the normal ranges reported by the manufacturer at all time points.22 Likewise, platelet aggregation in hirudin-anticoagulated whole blood did not

Conclusions

In the present randomized clinical trial, the whole blood POC assays TEM and MEA did not demonstrate significant differences in either coagulation or platelet function in patients anticoagulated with a high or standard dose of heparin during cardiac surgery. Therefore, although the higher dose of heparin was as safe as the lower dose, regarding POC measurements, it does not seem to offer any benefit.

Conflict of Interest

None.

References (32)

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This work was supported by research funding from the Finnish Ministry of Social Affairs and Health.

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