Haemoglobinopathies Quiz

A 28-year-old lady presents with a first pregnancy. She has recently emigrated to this country from India and has no medical records. She is unaware of any pre-existing illnesses and has not been transfused before. By her last menstrual period, she is 12 weeks pregnant. On examination, there is conjunctival pallor and mild hepatosplenomegaly. Booking scans are organised. Initial investigations reveal:

Haemoglobin 8.2 g/dL (11.4-14.7)
MCV 58fL (83.0-95.5)
RBC 4.56×10¹²/L (4.00-5.20)
RDW 14.0% (10.9-14.3)
Platelets 428×10⁹/L (164-387)
WBC 7.8×10⁹/L (3.84-10.01)

Iron 37.2µmol/L (9.5-30.0)
Ferritin 1513 µg/L (20-300)
Transferrin 218 mg/dL (200-360)
TIBC 57% µmol/L (52-94)
Iron saturation 66% (20-50)

HbA 90% (96.8-98.3)
HbA2 4.0% (1.7-3.2)
HbF 6.0% (0.0-1.0)

What is the most likely underlying diagnosis?

Why is her ferritin raised?

The patient is surprised to learn that she has β thalassaemia intermedia. She asks what the chance of her baby being affected is.

Based on the clinical information provided above, what is her likely genotype?

You ask to screen the baby’s father. His investigations are shown below:

Haemoglobin 11.1 g/dL (13.1-16.6)
MCV 71fL (83.0-95.5)
RBC 5.87×10¹²/L (4.00-5.20)
RDW 14.2% (10.9-14.3)
Platelets 365×10⁹/L (164-387)
WBC 5.4×10⁹/L (3.84-10.01)

HbA 95% (96.8-98.3)
HbA2 4.5% (1.7-3.2)
HbF 0.5% (0.0-1.0)

Based on the most likely paternal genotype, how would you counsel the patient?

She is offered pre-natal diagnosis, which she declines. Her pregnancy proceeds uneventfully, and she delivers a baby. She would like to know if the baby is affected by β thalassaemia.

How would you counsel the patient?

A year after delivery, the patient attends for a routine health check-up. Investigations as shown below:

Haemoglobin 8.2 g/dL (11.4-14.7)
MCV 58fL (83.0-95.5)
RBC 4.56×10¹²/L (4.00-5.20)
RDW 14.0% (10.9-14.3)
Platelets 428×10⁹/L (164-387)
WBC 7.8×10⁹/L (3.84-10.01)

HbA1c 8.5% (4.0-5.5%)

Albumin 31g/L (38-48)
Bilirubin, total 48µmol/L (5-30)
Bilirubin, conjugated 22µmol/L (0-5)
Bilirubin, unconjugated 26µmol/L (5-25)
AST 335U/L (10-50)
ALT 562U/L (10-70)
ALP 120U/L (40-130)
LDH 560U/L (250-580)

How would you investigate her abnormal liver function tests?

The patient has significant liver iron loading.

How would you manage her?

Due to financial constraints, the patient is started on deferiprone. A few weeks later, she attends a regular follow-up visit with a fever and sore throat.

What is the most important investigation to order?

Deferiprone is stopped and the patient is started on deferoxamine. She remains well with improvement in her liver function tests. A few years later, she presents with fever.

Haemoglobin 5.1 g/dL (11.4-14.7)
MCV 56fL (83.0-95.5)
RBC 2.56×10¹²/L (4.00-5.20)
RDW 13.8% (10.9-14.3)
Platelets 367×10⁹/L (164-387)
WBC 6.4×10⁹/L (3.84-10.01)

Reticulocyte count: 0.1% (0.5-2.5%)

What is the most likely diagnosis?