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Defining a reference range for cold agglutinin titers
Brenda J Bendix1, Craig D Tauscher, Sandra C Bryant
1Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota.
Insights
Cold agglutinin (CAGG) titers in healthy donors are lower than in patients with cold agglutinin disease (CAD). This study established new reference ranges, finding no seasonal variation but a sex association in patients.
Area of Science:
- Hematology
- Clinical Chemistry
Background:
- Cold agglutinin (CAGG) titer testing is crucial for diagnosing cold agglutinin disease (CAD).
- Existing reference ranges may not accurately reflect healthy populations.
Purpose of the Study:
- To establish a seasonally adjusted reference range for CAGG titers using prospective samples from healthy blood donors.
- To compare this new reference range with retrospectively generated ranges from patient cohorts.
Main Methods:
- Prospective CAGG titer testing on healthy blood donors in January and July.
- Retrospective analysis of patient CAGG titers using current and historical methods, excluding CAD-associated conditions.
- Verification of results using reference range program volunteers.
Main Results:
- No significant age or seasonal variation in CAGG titers was observed in blood donors or historical patient cohorts.
- A significant sex association was found in the current patient cohort (males: 64-512, females: ≤64).
- Prospective blood donor CAGG titers showed a lower 95% reference range (≤4) compared to historical (≤32) and current (≤64) patient cohorts.
Conclusions:
- Prospective CAGG titers from healthy blood donors are lower than those from retrospective patient cohorts.
- This difference may indicate that blood donors represent a healthier population, necessitating distinct reference ranges.
Background:
The cold agglutinin (CAGG) titer is offered at our institution to aid in diagnosing cold agglutinin disease (CAD). Our goal was to create a seasonally adjusted reference range using prospective samples and compare it to a reference range generated retrospectively.
Study Design And Methods:
Prospective CAGG titer testing was performed on healthy blood donors. Retrospective electronic analysis was performed on patients in two groups defined by current and historical testing methods. Blood donor testing was performed in January and July to determine if seasonal variation existed. Retrospective patients with conditions associated with CAD were excluded from analysis. Additional prospective CAGG testing using reference range program volunteers was performed to verify blood donor and patient result differences.
Results:
Titers from the blood donor and patient cohorts had no age association (p > 0.44). Titers from those same cohorts did not show winter/summer variation (p > 0.11). No sex association was found with titer reference ranges in the blood donor and historical patient cohort. A sex association was found with titers in the current method patient cohort (male 64 to 512 and female ≤64; p < 0.0001). Blood donor CAGG titer lower 95% reference range was not more than 4 while historical and current patient cohorts ranges were not more than 32 and not more than 64, respectively. Reference range volunteers confirmed the narrow reference range in healthy individuals when compared to patients and blood donors.
Conclusion:
Prospective blood donor CAGG titers were lower than retrospective patient cohorts. This may be due to blood donors representing a healthier population than the patient cohorts.
