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William Aird – Acute Rise in Total Protein Without Any Change in Albumin: What’s the Best Explanation?
William Aird/X
Dec 29, 2025, 21:46

William Aird – Acute Rise in Total Protein Without Any Change in Albumin: What’s the Best Explanation?

William Aird, Professor of Medicine at Harvard Medical School, posted on X:

“1/7

I recently posted a poll showing an acute rise in total protein without any change in albumin.

Total protein increased from 7.3 → 8.3 → 8.5 g/dL over just 10 days, while albumin stayed ~4.3 g/dL.

The question was: What’s the best explanation?

William Aird - Acute Rise in Total Protein Without Any Change in Albumin: What’s the Best Explanation?

2/7

The answer chosen by 52.9% (the majority) was polyclonal hypergammaglobulinemia.

Here’s the reasoning.

William Aird - Acute Rise in Total Protein Without Any Change in Albumin: What’s the Best Explanation?

3/7

Key principle:

If total protein rises but albumin stays flat, the increase is almost always in the globulin fraction, especially gamma globulins.

This immediately narrows the differential.

4/7

Why the other options don’t fit:

  •  Hemoconcentration → albumin and total protein rise together
  •  MGUS → does not develop over days to weeks
  •  Nephrotic syndrome → albumin falls, total protein often falls

So none explain an acute, isolated rise in total protein.

5/7

That leaves polyclonal hypergammaglobulinemia, which may be:

  •  Endogenous (inflammation, immune activation, autoimmune disease)
  •  Exogenous (IVIG administration)

Same lab pattern, different source.

6/7

In this case, the patient was on immune checkpoint inhibitor therapy and developed acute hepatitis and hemolytic anemia, a classic setup for robust endogenous polyclonal Ig production, explaining the rapid rise and persistence.

7/7

Teaching pearl:

Stable albumin = globulin problem.
Acute timing = polyclonal until proven otherwise.”

More posts featuring William Aird on Hemostasis Today.

Albumin gamma globulins Health Hemoconcentration Hemostasis Hemostasis Today Medicine MGUS Nephrotic syndrome polyclonal hypergammaglobulinemia Protein thrombosis William Aird
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