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William Aird: Rethinking Hemolysis Classification
William Aird/X
Oct 13, 2025, 04:58

William Aird: Rethinking Hemolysis Classification

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

“1/6

RETHINKING HEMOLYSIS CLASSIFICATION

I recently saw an incredibly rare but fascinating case of T-cell large granular lymphocytic (T-LGL)–mediated, DAT-negative hemolysis.

It prompted me to rethink how we classify hemolytic anemia and revise the schematic accordingly.

William Aird: Rethinking Hemolysis Classification

2/6

We usually divide hemolysis into immune and non-immune:

  • Immune → antibody-mediated (autoimmune or alloimmune), DAT-positive
  • Non-immune → mechanical, microangiopathic, infectious, toxic

That framework covers >99% of cases.

3/6

But what about the ultra-rare, cell-mediated form, when cytotoxic T or NK cells directly attack red cells or precursors?

  • No antibodies.
  • No complement.
  • DAT-negative.

Mechanism: perforin/granzyme or Fas–FasL–mediated cytotoxicity.

4/6

These are not theoretical.

Occasional cases of LGL leukemia have shown evidence of direct, antibody-independent RBC destruction, essentially a cell-mediated immune hemolysis.

Vanishingly rare, but biologically fascinating.

5/6

So, I’ve updated the diagram.

Under “Immune hemolysis,” I’ve added a side branch:

“Cell-mediated (T/NK-cell cytotoxicity, DAT-negative)”

It’s a footnote in clinical reality but makes the schema more complete for those who enjoy a good hematologic deep dive.

William Aird: Rethinking Hemolysis Classification

6/6

If you teach or think about hemolysis, this nuance helps connect the adaptive (antibody-mediated) and cellular (cytotoxic) arms of immunity.

Sometimes the exceptions are what remind us how beautifully complex blood can be.”

Stay updated with Hemostasis Today.

DAT-negative hemolysis Health Hematology Hemolysis Classification Hemostasis Hemostasis Today LGL leukemia Medicine NK Cells T-cell T-LGL William Aird
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