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?
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1. Let's begin with definitions - lymphopenia is usually defined as an absolute lymphocyte count ALC <1000 cells/microL for adults Image
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2. Epidemiology - lymphopenia has been documented in 1.5-3% of CBCs from both community and hospitalized patients. Image
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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
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4. Mechanisms - reduced production, increased destruction, increased apoptosis, redistribution of lymphocytes between blood and various lymphoid tissues. Image
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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
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6. History and physical - focus on symptoms/signs associated with underlying cause/associated conditions(s). Image
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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

Oct 21
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
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
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
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
Aug 26
1/5

SPLENOMEGALY/HYPERSPLENISM

Mechanisms of splenomegaly:
• Congestive
• Work hypertrophy
• Infiltrative

What enlarges?
• Red pulp: macrophages, sinusoids, blood
• White pulp: lymphocytes, plasma cells
• Infiltrative: tumor, storage cells, granulomas, amyloid

#MedEd Image
2/5

SPLENOMEGALY/HYPERSPLENISM

Red pulp = ~75% of spleen, the “filter & reservoir.”

Site of pooling, culling & destruction → main driver of splenomegaly + hypersplenism.

Open circulation = quality control: normal cells pass, rigid ones get removed. Image
3/5

Splenomegaly → hypersplenism when an enlarged spleen starts causing cytopenias:

• Pooling (cells trapped in red pulp)
• Destruction (macrophage culling)

→ ↓ platelets>WBCs>RBCs

All hypersplenism comes with splenomegaly, but not all splenomegaly causes hypersplenism Image
Read 5 tweets
Jan 19
1/7

I posted the graphic below earlier in the week and asked what was missing.

Before addressing the question, let's flesh out the various diagnostic containers.

1. HEMOLYSIS:

Immune hemolysis:
Autoimmune
Warm, Cold, Mixed
Alloimmune
ATR, DTR Image
2/7

Non-immune hemolysis
Intracapsular
Hemoglobinopathies
Membrane disorders
Hbopathies

Extracorpuscular
Infection (babesiosis, malaria, clostridial)
Liver (spur cell anemia, Zieve syndrome)
TMA
3/7

Non-immune hemolysis (cont'd)
Extracorpuscular
Valve hemolysis
March hemoglobinuria
Venom
Hyperthermia

2. BLEEDING:

External:
Hemorrhage
Phlebotomy
Internal (hematoma)
Read 7 tweets

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