The Relationship between Systemic Anticoagulation during Cardiac Surgery and Heparin Platelet Factor 4 Antibody Formation.

Heparin-induced thrombocytopenia occurs in approximately 1–3% of patients receiving unfractionated heparin. However, up to 50% of patients receiving heparin for systemic anticoagulation during cardiac surgery with cardiopulmonary bypass develop antibodies to the heparin-platelet factor 4 (HPF4) complex detectable by enzyme-linked immunoassays (ELISA). This high incidence of seroconversion is not diminished by off-pump cardiac surgery (OPCAB), despite significantly lower doses of heparin used for surgical anticoagulation. We tested the hypothesis that HPF4 antibodies develop following cardiac surgery even when heparin is not used for surgical anticoagulation. Patients (n=133) were randomized (2:1) to receive bivalirudin (The Medicines Company, Parsippany, NJ) or heparin for surgical anticoagulation during OPCAB. There were no restrictions on the pre-operative or post operative use of heparin. Blood samples were obtained pre-operatively (baseline), and 7 and 30 days after surgery. Serum samples were stored frozen until tested with a commercially available ELISA for HPF4 antibodies (GTI Inc., WI). An optical density (OD) ≥ 0.4 was considered positive, while an OD >1.0 was deemed strongly positive. The percentage of patients having a positive HPF4 antibody test (OD ≥ 0.4), was similar at baseline (6.7 vs. 6.8%) and at 7 days (27.1 vs. 29.3%) in bivalirudin and heparin-treated patients, respectively. At 30 days, the frequency of HPF4 antibodies was lower in the patients who received bivalirudin for surgical anticoagulation (32.5% vs. 40.9%). The percentage of patients having a strongly positive ELISA (OD > 1.0) was 0% at baseline in both groups, 4.3 vs. 7.3% at 7 days and 4.8 vs. 9.1% at 30 days for bivalirudin vs heparin, respectively. These data suggest that HPF4 antibody formation during hospitalization for cardiac surgery is not dependent only on the heparin used for anticoagulation during surgery. Antibody positivity in baseline samples presumably results from pre-operative heparin use and is consistent with previous reports. Since bivalirudin is not capable of eliciting an HPF4 antibody response, post-operative seroconversion presumably reflects a combination of both pre- and post-operative heparin use. However, when heparin was used for surgical anticoagulation, the number of patients subsequently developing strongly positive HPF4 antibodies was almost twice that seen in the bivalirudin group. This suggests that the use of bivalirudin as a surgical anticoagulant may reduce the incidence and risk of HIT following cardiac surgery.