William Aird: SPURIOUS MACROCYTOSIS FROM HYPERLEUKOCYTOSIS

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

“SPURIOUS MACROCYTOSIS FROM HYPERLEUKOCYTOSIS

Yesterday, I tweeted 2 CBCs from a patient 4 months apart and asked for an explanation of the de novo macrocytosis. I also showed a WBC differential and asked whether the patient was neutropenic.

Lots of awesome responses! Shout out to Uriel Suárez and J Lee for correctly answering both questions. Let’s deal with the 2nd question 1st. The neutrophil count was 1% but none of you fell for the trap and labeled this neutropenia. The ANC was a healthy 3.3 x 10^9/L!

Now for the first question. Many of you guessed that the patient developed AIHA as a complication of evolving CLL, with reticulocytosis-associated macrocytosis. That works, but there are two pieces of data that is tough to reconcile:

1. Reticulocytes are normally 20-30% larger than mature RBCs. That means that even with 100% retics, the MCV will not typically reach 122 fL (this patient’s level). So reticulocytosis is an unlikely explanation simply based on the degree of macrocytosis.

2. The MCHC falls from 34.6 to 25.3. That’s a huge drop over 4 months, and we rarely ever see MCHCs this low. It’s true that reticulocytosis may be associated with a certain degree of hypochromia (remember, their Hb becomes more concentrated as the cell matures)… but not to this low level. This is a case of spurious macrocytosis caused by hyperleukocytosis in CLL. RBCs are counted and sized along with WBCs and platelets using the Coulter method in automated hematology analyzers.

Normally, the number of WBCs is too small to affect the RBC parameters. However, in some cases of hyperleukocytosis, the number and size of WBCs may influence the RBC indices (falsely elevated RBC count and MCV, and because MCHC = Hb/Hct, falsely low MCHC).

Appropriate corrections can be made to estimate the correct Hct, MCV and MCHC (see second graphic).”

Source: William Aird/X