Yesterday I posted CBCs from a patient, posed three questions and asked for a diagnosis.
Kudos to @EltonWandira for coming up with the answers and diagnosis within minutes of posting!
The dx is CAD.
2/9
Answers to questions:
Q1. Which value at time 0 is physiologically impossible?
A1. The MCHC of 65.4 g/dL. Hb is almost supersaturated under normal conditions, and rarely increases above 40 g/dL.
3/9
Q2. What does the notation 4 refer to at time 0?
A2. Spun Hct. Note that the Hb is reported as 8.5 g/dL, the Hct as 26.5%. Recall that the MCHC = Hb/Hct, which in this case would = 32 g/dL, a far cry from the reported MCHC of 65.4 g/dL!
4/9
Q3. What has the lab technician done to the blood to obtain 4 h results?
A3: They have warmed the blood to disassemble the cold agglutinins from the RBCs, converting clumps to single cells.
5/9
Instead of simply memorizing this pattern of CBC changes in CAD, let's think our way through it.
In automated hematology analyzers ('CBC machines'), RBCs normally pass in single file as their numbers are counted and their volume measured using the Coulter principle.
6/9
In CAD, clumps of 3 or more RBCs cannot squeeze through the aperture used for counting/sizing cells, so fewer cells get through, leading to falsely low RBC count. Doublets can pass through, but are counted as single cells, resulting in falsely high MCV and reduced RBC count.
7/9
These artefactual changes can be incorporated in the equation Hct = RBC count x MCV. Because the RBC takes a double hit, it is disproportionately decreased relative to the change in MCV, resulting in a reduction in Hct.
8/9
Finally because the Hct is falsely low (and the Hb is one of the few parameters unaffected in CAD), the MCHC is falsely elevated.
9/9
We can put it all together in table format with findings and explanations.
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A woman with ferritin 10 and Hb 12.2 (baseline 14). How should this be described?
Here’s how you answered:
• non-anemic Fe deficiency: 35%
• Fe deficiency anemia: 32%
• Fe deficiency with relative anemia: 27%
• none: 6%
Really interesting spread!
2/11
This tells us something important: clinicians sense a mismatch between definition-based language and physiology-based thinking, even if we disagree on terminology.
3/11
By strict WHO criteria, she is not anemic.
Hb ≥12 in women = normal.
So formally the correct label is: iron deficiency without anemia.
In acute GI bleed anemia, would you give 1 g IV iron regardless of ferritin?
Results:
• 27% yes — anticipate iron debt
• 12% sometimes
• 21% only if ferritin is low
• 41% no
2/13
First, an important acknowledgment:
There is no right answer here.
There are no firm guidelines that tell us what to do in this situation. Reasonable clinicians land in different places.
This is a gray zone where physiology, timing, and judgment matter.
3/13
So rather than argue what we should do, I want to walk through the numbers and biology and explain why some clinicians anticipate iron debt even when ferritin is normal.
Yesterday I posted a CBC + reticulocyte count and asked for your diagnostic thoughts. Many of you offered great reasoning. The correct diagnosis was hemoglobin C disease.
Let’s unpack why this case is such a good learning example. 👇
2/9
Microcytosis often triggers a reflex binary:
iron deficiency vs thalassemia trait.
That’s a useful starting point. But it’s incomplete. Structural hemoglobin variants (like HbC and HbE) also belong on that list.
3/9
Several people calculated the Mentzer index (MCV/RBC):
75 / 4.0 ≈ 18 → “suggests iron deficiency (ID).”
Important teaching point:
The Mentzer index was designed to distinguish thal trait vs ID. It is not validated for structural hemoglobinopathies like HbC or HbE.