P-II-4. Liver disease, Case 1

A 15-year-old boy noticed that his skin had turned yellow after a viral infection 3 days ago. It was accompanied by vomiting and diarrhoea. He had previously experienced jaundice following major physical or psychological stress but did not pay much attention to it as the complaint resolved spontaneously. However, at this time, he had weakness, dizziness, headache, and shortness of breath after exertion; therefore, he consulted his GP.

The doctor initially suspected Gilbert’s syndrome because of intermittent icterus and attributed the other symptoms to the viral illness. On physical examination, he found splenomegaly as well.

Then, in order to make a definitive diagnosis, the doctor consulted the patient’s mother, who reported that her son had prolonged icterus after birth, which was successfully treated with phototherapy and phenobarbital. In addition, her husband had intermittent icterus, and her son’s paternal grandfather had to have his spleen and gall bladder removed as a child because of severe jaundice.

The initial questions about the nature of the disease were answered clearly by the laboratory tests and blood smears requested by the GP.

Laboratory test — Blood:

• white blood cell: 12 G/L
• red blood cell: 3.2 T/L
• HGB: 80 g/L
• Ht: 0.3
• MCV: 92 fL
• MCH: 28.6 pg (normal)
• MCHC: 380 g/L (high)
• RDW: 19% (high)
• reticulocyte: 10%
• ASAT: 19 U/L
• ALAT: 23 U/L
• total bilirubin: 33 μmol/l
• direct bilirubin: 5.2 μmol/l
• LDH: 250 U/L (high)
• haptoglobin, haemopexin: low
• direct Coombs reaction: negative
• osmotic fragility test: abnormal

Urine:

• UBG: elevated
• bilirubin: negative
• HGB: positive

Blood smear:

• hyperdense, small, spherical-shaped cells
• anisocytosis, poikilocytosis

---

Key Quotes & What They Tell Us

Quote / Value	Interpretation
Blood smear: “hyperdense, small, spherical-shaped cells”; osmotic fragility “abnormal”	Spherocytes with increased osmotic fragility → a membrane defect causing red-cell destruction
Family history: father intermittent icterus; grandfather splenectomy + gallbladder removed; neonatal jaundice	Autosomal-dominant inherited haemolytic disorder → hereditary spherocytosis
HGB 80 g/L; reticulocyte 10%; MCHC 380 (high); RDW 19% (high)	Anaemia with brisk reticulocyte response and hyperchromic, variable-sized cells → active haemolysis with marrow compensation
Total bilirubin 33, direct only 5.2 µmol/L; urine bilirubin negative, UBG elevated	Unconjugated (indirect) hyperbilirubinaemia → pre-hepatic/haemolytic jaundice
LDH high; haptoglobin/haemopexin low; urine HGB positive	Intravascular/extravascular haemolysis markers (released LDH, consumed haptoglobin, haemoglobinuria)
Direct Coombs negative	Excludes autoimmune haemolysis → supports an intrinsic membrane defect
Splenomegaly	Spleen traps and destroys abnormal spherocytes

Key Points

• Diagnosis: Hereditary spherocytosis causing chronic haemolytic anaemia and pre-hepatic jaundice.
• Pathophysiology: Inherited red-cell membrane protein defect → spherical, less deformable cells → splenic destruction → haemolysis.
• Jaundice type: Unconjugated hyperbilirubinaemia (negative urine bilirubin, raised urobilinogen) — not a hepatocellular or obstructive cause.
• Triggers: Haemolysis worsens with infection/stress (explaining intermittent icterus).
• Key discriminators: Negative Coombs (not autoimmune), abnormal osmotic fragility, spherocytes on smear, and strong family history.
• Complications: Pigment gallstones (hence the grandfather’s gallbladder removal) and the need for splenectomy in severe disease.