A 28-year-old man of Punjabi descent presents to the outpatient clinic with complaints of mild fatigue and jaundice noted incidentally on routine examination. His hemoglobin is 9.8 g/dL, MCV 72 fL, and reticulocyte count is 8% (normal 0.5–2%). Peripheral blood smear reveals target cells, polychromasia, and occasional nucleated RBCs. Serum bilirubin is 3.2 mg/dL (indirect predominant), and haptoglobin is

Question

A 28-year-old man of Punjabi descent presents to the outpatient clinic with complaints of mild fatigue and jaundice noted incidentally on routine examination. His hemoglobin is 9.8 g/dL, MCV 72 fL, and reticulocyte count is 8% (normal 0.5–2%). Peripheral blood smear reveals target cells, polychromasia, and occasional nucleated RBCs. Serum bilirubin is 3.2 mg/dL (indirect predominant), and haptoglobin is <10 mg/dL. Direct antiglobulin test (DAT/Coombs) is negative. What is the most likely diagnosis?

Accepted Answer

D. Beta-thalassemia trait. ## Diagnostic Approach

This patient presents with a **chronic hemolytic anemia** with specific features pointing to **beta-thalassemia trait (heterozygous state)**.

### Key Clinical & Laboratory Findings

**Hematologic profile:**
  - Mild anemia (Hb 9.8 g/dL) — relatively preserved despite hemolysis
  - **Microcytic** (MCV 72 fL) — hallmark of thalassemia
  - **Elevated reticulocyte count** (8%) — appropriate bone marrow response to hemolysis
  - Target cells on smear — classic in thalassemia
  - Nucleated RBCs — sign of extramedullary erythropoiesis

**Hemolysis markers:**
  - Indirect hyperbilirubinemia (3.2 mg/dL)
  - Low haptoglobin (<10 mg/dL) — consumed by hemoglobin-haptoglobin complexes
  - **Negative DAT** — rules out immune-mediated hemolysis

**Ethnic context:**
  - Punjabi descent — thalassemia is endemic in Northern India, particularly Punjab
  - Chronic, mild presentation consistent with trait (not disease)

### Why Beta-Thalassemia Trait?

**High-Yield:** The combination of:
  1. Microcytic anemia (MCV <75 fL)
  2. Elevated reticulocyte count (appropriate hemolytic response)
  3. Target cells + nucleated RBCs
  4. Negative DAT (not immune hemolysis)
  5. Endemic population
  
...is pathognomonic for **beta-thalassemia trait**.

**Key Point:** Beta-thalassemia trait (heterozygous) is often asymptomatic or mildly symptomatic and discovered incidentally. The microcytic anemia is disproportionate to the degree of hemolysis.

### Differential Diagnosis Table

| Feature | β-Thalassemia Trait | Hereditary Spherocytosis | AIHA | G6PD Deficiency |
|---------|---|---|---|---|
| MCV | **Micro** | Normal/Macro | Normal | Normal |
| Target cells | **Yes** | No | No | No |
| DAT/Coombs | Negative | Negative | **Positive** | Negative |
| Haptoglobin | Low | Low | Low | Low |
| Reticulocyte | Elevated | Elevated | Elevated | Elevated (acute) |
| Nucleated RBCs | **Yes** | Rare | Rare | Rare |
| Osmotic fragility | Normal | **Increased** | Normal | Normal |
| Trigger | Chronic | Chronic | Chronic | Oxidative stress |

**Mnemonic for Thalassemia Trait findings: "MiTT"**
  - **Mi**crocytic (MCV <75)
  - **T**arget cells
  - **T**rait (heterozygous, asymptomatic)

**Clinical Pearl:** In beta-thalassemia trait, the degree of microcytosis is out of proportion to the anemia severity. This is because both hemolysis AND ineffective erythropoiesis contribute to the low MCV.

![Anemias Overview diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2615.webp)

Answer

A. G6PD deficiency with acute hemolysis

Answer

B. Hereditary spherocytosis

Answer

C. Autoimmune hemolytic anemia

Explanation

Diagnostic Approach

Key Clinical & Laboratory Findings

Why Beta-Thalassemia Trait?

Differential Diagnosis Table

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Feature	β-Thalassemia Trait	Hereditary Spherocytosis	AIHA	G6PD Deficiency
MCV	Micro	Normal/Macro	Normal	Normal
Target cells	Yes	No	No	No
DAT/Coombs	Negative	Negative	Positive	Negative
Haptoglobin	Low	Low	Low	Low
Reticulocyte	Elevated	Elevated	Elevated	Elevated (acute)
Nucleated RBCs	Yes	Rare	Rare	Rare
Osmotic fragility	Normal	Increased	Normal	Normal
Trigger	Chronic	Chronic	Chronic	Oxidative stress