Hemoglobinopathy

John Matthews and Dilys Rapson

 Hemoglobin structure

heme
Hemoglobins in normal adults

HbA HbF HbA2

98% ~1% <3.5%

 Hemoglobin structure

heme
Heme
Globin
The Oxygen Dissociation Curve
pVO2 pAO2

normal e.g. 22

abnormal e.g. 4
 Hemoglobin synthesis
25% 25% 0.5% 1.5% 48%

25% 25% 0.5% 1.5% 48%

Chromosome 16 Chromosome 11
 Hemoglobinopathy
definition

An inherited mutation of the globin

genes leading to a qualitative or
quantitative abnormality of globin
synthesis
Structural hemoglobinopathy

Amino acid substitution in the globin

chain e.g. sickle hemoglobin (HbS)
 The Thalassemias

Syndromes in which the rate of synthesis of a

globin chain is reduced
beta thalassemia - reduced beta chain
synthesis
alpha thalassemia reduced alpha
chain synthesis
 Sickle Cell Anemia (HbSS)
1. 6 glu to val
2. tactoids at low oxygen tension
3. sickled red cells
4. small blood vessel occlusion
5. tissue infarction
Sickle Cell Anemia blood film

Sickle
Cells

Erythroblasts
Howell-
Jolly Body
Sickle Cell
Anemia

EM of red
cell showing
tactoids
Sickle cell anemia clinical features

1. Hemolysis
2. Occlusion of blood vessels by sickled
red cells
Anemia Cause Management
Hemolytic Removal of Transfusion for
anemia irreversibly certain indications.
sickled cells by Folate supplements.
macrophages Iron chelation if
chronic transfusion
Aplastic Parvovirus B19 Transfusion
crisis
Site of Clinical Management
Sickling Features
Bone Painful crises Pain relief and hydration.
Hydroxyurea
Lung Acute chest Transfusion regimen,
syndrome pain relief and hydration
Brain Stroke Transfusion regimen.
Heart Myocardial Transfusion regimen,
infarction pain relief and hydration
Spleen Acute splenic Transfusion, pain relief
sequestration: and hydration
Spleen Hyposplenism: Pneumovax
Retina Proliferative Retinal surveillance.
retinopathy Laser
Sickle Cell Anemia - treatment
Opiates and hydration for painful crises
Pneumococcal vaccination
Retinal surveillance
Hydroxyurea
Transfusion for serious manifestations
Stem cell transplant
Support, folate, iron chelation
 Sickle Cell Trait
Heterozygous state for HbS (HbAS)
No serious clinical consequences
Sudden death during intensive training
Hematuria, isosthenuria (renal papillary
necrosis)
 Beta thalassemia

Impaired production of beta chain

beta thalassemia minor heterozygous (or trait)
beta thalassemia major - homozygous
Beta thalassemia trait

No symptoms
Mild microcytic anemia
 Beta thalassemia major
No beta chain produced (no HbA)
Severe microcytic anemia occurs
gradually in the first year of life
Marrow expansion
Iron overload
Growth failure and death
Beta thalassemia major
Male 18 years
Beta thalassemia major
treatment

Transfusion
Iron chelation
Stem cell transplant
 Alpha thalassemia
/ Normal

/- Mild microcytosis

/- - Mild microcytosis
-/-
-/- - Hemoglobin H disease

- -/- - Hemoglobin Barts Hydrops Fetalis

Hemoglobinopathy-antenatal
diagnosis

Test partners of heterozygous

or affected individuals
Antenatal diagnosis from DNA
obtained by chorionic villus
sampling, or by amniocentesis