I am referred occasional otherwise healthy patients for evaluation of lymphopenia (aka lymphocytopenia).
What to do?
2/8
1. Let's begin with definitions - lymphopenia is usually defined as an absolute lymphocyte count ALC <1000 cells/microL for adults
3/8
2. Epidemiology - lymphopenia has been documented in 1.5-3% of CBCs from both community and hospitalized patients.
4/8
3. Causes/associated conditions - lymphopenia may be found incidentally in someone without obvious underlying cause (most common) or may be associated with a number of diseases/conditions.
5/8
4. Mechanisms - reduced production, increased destruction, increased apoptosis, redistribution of lymphocytes between blood and various lymphoid tissues.
6/8
5. Clinical implications - no evidence (outside of large population studies that do not take into account underlying cause) that lymphopenia associated with increased risk of infection.
7/8
6. History and physical - focus on symptoms/signs associated with underlying cause/associated conditions(s).
8/8
7. Lab tests - generally not needed in an otherwise healthy individual.
8. Treatment - directed towards the underlying cause.
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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.