William Aird Profile picture
Jul 17, 2023 8 tweets 3 min read Read on X
1/8

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 Image
3/8

2. Epidemiology - lymphopenia has been documented in 1.5-3% of CBCs from both community and hospitalized patients. Image
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. Image
5/8

4. Mechanisms - reduced production, increased destruction, increased apoptosis, redistribution of lymphocytes between blood and various lymphoid tissues. Image
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. Image
7/8

6. History and physical - focus on symptoms/signs associated with underlying cause/associated conditions(s). Image
8/8

7. Lab tests - generally not needed in an otherwise healthy individual.

8. Treatment - directed towards the underlying cause. Image

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More from @WilliamAird4

Feb 2
1/13

I posted a poll asking:

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.

Let’s take a concrete example.
Read 13 tweets
Jan 23
1/9

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. 👇 Image
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.
Read 9 tweets
Oct 21, 2025
1/7

A STRUCTURED APPROACH TO NORMOCYTIC ANEMIA

A practical, population, and molecular look at how we reason through normocytic hypoproliferative anemia at the bedside.

(Full TBP tutorial linked below ⬇️)
2/7

1️⃣ The ABC Spine – A Bedside Framework

A: substrate supply (nutritional)
B: regulatory signaling (inflammatory)
C: organ dysfunction (kidney, liver, endocrine, marrow)

We focus here on the hypoproliferative end of the spectrum, where the marrow is not keeping up. Image
3/7

2️⃣ Anemia of the Elderly – A Population Perspective

In older adults, causes divide roughly:

1/3 nutritional 
1/3 inflammatory
1/3 unexplained

Each slice maps back to A, B, or C of the spine. Image
Read 7 tweets
Oct 7, 2025
IV IRON AND FERRITIN

1/8

I recently posted a question about the spike in serum ferritin after IV iron.

It can shoot from <10 to >1000, yet transferrin saturation (TSAT) only rises to normal — it barely moves.

What’s going on?

This is macrophage physiology in action 👇 Image
2/8

Step 1 – Uptake

IV iron–carbohydrate complexes (e.g., iron dextran) are endocytosed by macrophages in the liver, spleen, and marrow.

Inside, the iron is released and floods the labile Fe²⁺ pool, the cell’s internal “iron bank.”
3/8

Step 2 – Ferritin synthesis explodes

High intracellular Fe²⁺ flips the IRP–IRE switch, unleashing translational ferritin synthesis.

Cytokines add a transcriptional boost.

Ferritin production ↑↑ → serum ferritin rises via a regulated, non-classical secretion pathway.
Read 8 tweets
Oct 6, 2025
1/4

Patients with SLE can present with a staggering array of hematologic abnormalities. Virtually no component of the blood is spared. Everything is fair game:

1. Blood cells - cytopenia and cytoses
2. Hemostasis - thrombosis, TMA
3. Lymphadenopathy/splenomegaly
4. Lymphoma Image
2/4

Diagnostic criteria for SLE include the following hematological parameters:

1. Hemolytic anemia
2, Leukopenia
3. Lymphopenia
4. Thrombocytopenia
5. Anti phospholipid antibodies
3/4

The primary mechanisms of hematological alterations in SLE are:

1. Autoimmunity
2. Immunosuppressive medications

There is increasing appreciation that the disease targets not only peripheral blood cells but also the bone marrow leading to:

1. MF
2. PRCA
3. AA Image
Read 4 tweets
Sep 20, 2025
1/4

The Plasma Exchange Paradox

Have you ever wondered why plasma exchange saves lives in TTP but does nothing in ITP? Both are IgG-mediated. So why the difference?
2/4

In ITP, antibodies opsonize platelets. Even if you remove some by exchange, IgG quickly re-equilibrates from the extravascular pool and continues to be produced. With no missing factor to replace, there’s no lasting benefit.
3/4

In TTP, antibodies inhibit ADAMTS13. Plasma exchange not only removes antibody but also replaces the missing enzyme (and helps clear ULVWF multimers). That dual action is why it works.
Read 4 tweets

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