Heparin Dose Response Is Independent of Preoperative Antithrombin Activity in Patients Undergoing Coronary Artery Bypass Graft Surgery Using Low Heparin Concentrations

Abstract

BACKGROUND Unfractionated heparin’s primary mechanism of action is to enhance the enzymatic activity of antithrombin (AT). We hypothesized that there would be a direct association between preoperative AT activity and both heparin dose response (HDR) and heparin sensitivity index (HSI) in patients undergoing coronary artery bypass graft surgery. METHODS Demographic and perioperative data were collected from 304 patients undergoing primary coronary artery bypass graft surgery. AT activity was measured after induction of general anesthesia using a colorimetric method (Siemens Healthcare Diagnostics, Tarrytown, NY). Activated coagulation time (ACT), HDR, and HSI were measured using the Hepcon HMS Plus system (Medtronic, Minneapolis, MN). Heparin dose was calculated for a target ACT using measured HDR by the same system. Multivariate linear regression was performed to identify independent predictors of HDR. Subgroup analysis of patients with low AT activity (<80% normal; <0.813 U/mL) who may be at risk for heparin resistance was also performed. RESULTS Mean baseline ACT was 135 ± 18 seconds. Mean calculated HDR was 98 ± 21 s/U/mL. Mean baseline AT activity was 0.93 ± 0.13 U/mL. Baseline AT activity was not significantly associated with baseline or postheparin ACT, HDR, or HSI. Addition of AT activity to multivariable linear regression models of both HDR and HSI did not significantly improve model performance. Subgroup analysis of 49 patients with baseline AT <80% of normal levels did not reveal a relationship between low AT activity and HDR or HSI. Preoperative AT activity, HDR, and HSI were not associated with cardiac troponin I levels on the first postoperative day, intensive care unit duration, or hospital length of stay. CONCLUSION Although enhancing AT activity is the primary mechanism by which heparin facilitates cardiopulmonary bypass anticoagulation, low preoperative AT activity is not associated with impaired response to heparin or to clinical outcomes when using target ACTs of 300 to 350 seconds.

The incidence of heparin resistance in patients undergoing open heart surgery and an evaluation of treatment strategies: a retrospective study

“…[13,14] In our study, 32 of the 54 patients who developed HR were 65 years old or older, and 52 of these 54 had a platelet count of 300,000 or over. None of our patients who received preoperative heparin were included in the study since the preoperative AT-III activities of these patients were unknown.…”

“…None of our patients who received preoperative heparin were included in the study since the preoperative AT-III activities of these patients were unknown. Garvin et al, [14] showed that the preoperative AT-III level did not affect the heparin response but found that preoperative heparin only decreased AT-III activity. However, this decrease did not change the heparin dose response.…”

Antithrombin activity and heparin response in neonates and infants undergoing congenital cardiac surgery: a retrospective cohort study

“…12,13 Similar to other clinical studies investigating the relationship between AT and heparin responsiveness, we were unable to reproduce the strong positive association that exists in vivo between AT and heparin responsiveness. 10,16 This suggests that decreased heparin response in vivo is multifactorial, and the lack of a strong association between AT activity and heparin responsiveness may be a Table 1 Characteristics of neonates and infants undergoing congenital cardiac surgery…”

Heparin Sensitivity and Resistance

“…20 In vivo evidence confirms that an AT concentration less than 80% does in fact result in a higher incidence of heparin resistance. However, Garvin et al 23 demonstrated a low correlation, even in patients with an AT concentration less than 80%. However, Garvin et al 23 demonstrated a low correlation, even in patients with an AT concentration less than 80%.…”