A Phenomenon of Normal Total Bilirubin with Increased Direct Bilirubin Noted In Patients with Plasma Cell Dyscrasias

One of the authors noted the phenomenon of increased direct bilirubin with normal total bilirubin in patients with multiple myeloma and other plasma cell dyscrasias seen at our institute. This triggered a literature search regarding the same. Gammopathy interference in automated chemistry assays has been described before. Increased serum total bilirubin levels have been reported in patients with monoclonal gammopathy. There is also one report of decrease in direct bilirubin due to paraprotein interference. As far as we know the phenomenon noted by us has never been described before.

We retrospectively analyzed charts of 360 patients who had an abnormal serum protein electrophoresis since 2007. Patients who had multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), waldenstroms macroglobulinemia, light chain disease or primary amyloidosis and had total protein, albumin, total bilirubin and direct bilirubin performed, were included in the study. Patients who did not have all 4 tests done together were excluded. Patients with abnormal liver function tests due to liver disease were also excluded. A total of 211 patients were identified who met the inclusion criteria. Two hundred controls were also analyzed and they were selected as the 200 consecutive patients seen in general medicine service in the month of august 2010 who did not have liver disease or any plasma cell dyscrasia.

The bilirubin assays was performed using the OLYMPUS AU2700/AU5400 automated analyzers. Our direct bilirubin reagent utilizes a variation of the classical method developed by Van den Bergh and Mueller where direct bilirubin couples with a diazonium salt to form azobilirubin which is measured bichromatically. A similar procedure is used for total bilirubin where it forms azobilirubin after reacting with a diazonium salt and the absorbance is measured bichromatically.

Out of the 211 patients in the study group 23.7% (n=50) had a direct bilirubin higher than the total bilirubin. The total bilirubin value for all patients was within normal range. Of the control group 0% of the patients had direct bilirubin greater than the total bilirubin which was highly significant. Also noted was the fact that the patients in the study group with this observed lab phenomenon (n=50) had a higher mean protein gap (difference between total protein and albumin) of 6.18 g/dL compared to the patients who did not have this phenomenon (n=161), whose average protein gap was 3.77 g/dL. This value was significant with p 0.005 (95% CI 1.68–3.14) using the student t-test.

We observed a phenomenon where a normal total bilirubin with direct bilirubin higher than the total bilirubin was noted in patients with plasma cell dyscrasias. This could be due to interference with the bilirubin assays. Further studies are needed to see if this phenomenon may have clinical implications in the future, where physicians may be alerted to the presence of a possible paraprotienemia if they note this phenomenon on a patient's lab tests.

No relevant conflicts of interest to declare.