Tissue factor pathway inhibitor antigen and activity in 96 patients receiving heparin for cardiopulmonary bypass

Abstract

Objective: To identify patients with poor tissue factor pathway inhibitor (TFPI) response to heparin and observe any association with increased risk of excessive coagulation activation, morbidity, or mortality.

Design: Prospective, observational cohort study.

Setting: University hospital.

Participants: Patients (n = 96) undergoing cardiopulmonary bypass for various types of surgery.

Interventions: None.

Measurements and main results: TFPI antigen and activity were determined in patients before and after heparin administration, before cardiopulmonary bypass for cardiac surgery. The clinical progress of each patient was recorded. Median levels of TFPI activity were 0.98 U/mL (interquartile range, 0.83 to 1.14 U/mL) preheparin and 2.34 U/mL (2.18 to 2.54 U/mL) postheparin (p < 0.0001), representing a median 2.3-(2.1- to 2.8-) fold increase. Median TFPI antigen levels were 92.4 ng/mL (73.0 to 119.5 ng/mL) preheparin and 422.9 ng/mL (398.7 to 501.6 ng/mL) postheparin (p < 0.0001), representing a median 4.6-fold (3.6- to 6.2-fold) increase. Two patients had low (<300 ng/mL) postheparin levels of TFPI antigen that were not associated with low functional TFPI or adverse clinical outcome. Fourteen patients showed a low ratio of increased functional TFPI postheparin; all had a ratio of TFPI antigen increase of at least 3-fold.

Conclusion: The TFPI response to heparin is heterogenous. Two nonresponders were identified, with low postheparin levels of TFPI antigen, who did not suffer adverse clinical outcomes.