Seek and You Shall Find – but Then What Do You Do? Cold Agglutinins in Cardiopulmonary Bypass, and a Single Center Experience with Cold Agglutinin Screening Before Cardiac Surgery

Cardiopulmonary bypass (CPB) during cardiac surgery typically involves deliberate hypothermia of the systemic (22 – 36°C) and coronary circulations (down to 8 – 12°C). Adverse sequelae of previously undiagnosed cold-active antibodies have been feared and reported under such conditions. For this reason, some centers elect to screen for cold agglutinins prior to CPB. Some groups also intervene when a positive screen is noted, by electing to modify CPB conditions to lessen hypothermia in such patients.

To determine the yields and effects of cold agglutinin screening (CAS) in pre-operative cardiac surgery patients planned for CPB.

Literature review and retrospective cohort study of 14,900 patients undergoing CPB and cardiac surgery over 8 years at our institution.

The majority of the literature consists of case reports and case series. The literature review found that patients with a positive CAS had infrequent adverse events when undergoing CPB. These included 4 cases where complications were likely attributable to cold agglutinins, 4 cases where complications were possibly due to cold agglutinins and 158 cases where no complications were noted, despite a likely bias towards case reporting adverse events.

Analysis of a retrospective cohort of 14,900 patients undergoing CPB and cardiac surgery at our institution identified 47 patients (0.3%) with positive cold agglutinin screens (CAS+) over 8 years. The annual testing cost was $17,000 CAD.

Compared to the cohort of CAS-negative patients, CAS+ patients had a statistically longer ICU length of stay [median 54.6 hours (IQR 24 – 166) vs. 42.8 hours (IQR 23 – 70), P = 0.021] and hospital length of stay [median 7 days (IQR 6 – 14) vs. 7 days (IQR 5 – 9), P = 0.044]. However, the composite of mortality or severe morbidity (stroke, MI, dialysis, low output, sepsis, and DVT) was not significantly different in comparing the CAS+ and CAS-negative groups (14.9% vs. 9.2%, P = 0.2).

The response of the surgical team to the pre-operative discovery of a CAS+ patient was variable, with CPB modified to avoid hypothermia in approximately one-third of cases. Modification of CPB to avoid hypothermia in the CAS+ group did not lead to better outcomes. Patients undergoing unmodified (standard) CPB had an event rate of 10.3% on the composite outcome, while patients undergoing modified (less hypothermic) CPB had an event rate of 20.0% (P = 0.647).

Antibody verification found that only 43% of positive CAS patients had true cold agglutinins (20 patients). Half of these patients had unmodified CPB, while the other half had modified CPB. Event rates were low, with 1 out of 10 patients reaching the composite outcome in each group.

Based upon historical and local data, we conclude that preclinical CAS is cost-substantial, does not effectively identify true-positive patients, and does not lead to an intervention that meaningfully improves patient outcomes during surgery. We do not recommend CAS in asymptomatic cardiac surgery patients.

No relevant conflicts of interest to declare.