Haemoglobinopathies: Sickle-Cell Anaemia

sickle-cell anaemia

RBCs have an abnormal crescent shape making them sticky and rigid

Get trapped in small vessels and block blood from reaching different parts of the body- can cause pain and tissue damage.

Autosomal recessive condition- can be carrier

cause of sickle-cell anaemia

point mutation at position 6 on beta chain

A→T

glutamic acid → valine

HbAS- heterozygous (sickle-cell trait/carrier)

HbSS- homozygous (sickle-cell disease)

pathogenesis of sickle-cell anaemia

• in low oxygen conditions, Hb polymerises

• long fibres form crystals

• causes rigid “sickle” RBCs

causes obstruction of RBC circulation and anaemia from extravascular haemolysis

sickle cell disease (SCD) symptoms

Symptoms generally occur around 6-months

While there are multiple types of SCD, they all have similar symptoms at different levels of severity. These include:

• excessive fatigue or irritability (from anaemia)

• fussiness (in babies)

• bedwetting (from associated kidney problems)

• jaundice (yellowing of the eyes and skin)

• swelling and pain in hands and feet (ischemia)

• frequent infections (overworked spleen and ischemia)

• chest pain (Vaso-occlusive)

clinical picture of sickle-cell anaemia (acute)

Variable from patient to patient

• Mainly systemic: organ and tissue ischaemia.

• Episodes of crises:

  • Vaso-occlusive (VOC- sickle cells block blood vessels)

  • Visceral sequestration (VOC in spleen, leads to hypervolemic shock)

  • Aplastic (bone marrow stops making RBCs)

  • Haemolytic

• Chronic haemolytic anaemia

chronic haemolytic anaemia

• Sickle cells are destroyed early

• Chronic haemolysis sickle cells live for a maximum of 10 to 20 days.

• Heart Disease and Chest Syndrome low blood oxygen supply

• Enlarged heart and subsequent heart disease.

• High blood pressure (hypertension) and stroke may also develop. (7% of patients)

• Gallstones caused by the breakdown of RBCs. High levels of bilirubin can lead to gallstones.

• Delayed growth children.

How are haemoglobinopathies diagnosed?

• new-born screening

• detailed Patient History

• appearance of symptoms

• lab tests

haemoglobinopathies- FBCs and blood films

*polychromasia- multiple colours

Hb H bodies (golf balls)

from alpha thalassaemia

different from reticulocytes

basophilic stippling

beta thalassaemia

How can haemoglobin variants be detected?

cellulose acetate electrophoresis

cellulose acetate electrophoresis

another way to test the variant is to use

HPLC chromatography

POCT test for HbS

rapid solubility test

cloudy = positive result (sickle-cell)

sickle-cell disease treatment

depends on type and severity of disease involved

• Blood transfusions and chelation therapy

• Bone marrow transplant in children

• Medications and supplements (not iron if blood transfusions)

• Surgery to remove the spleen or gallbladder

• Gene therapy??

Taking care of yourself: Altitude • Pregnancy • Operations • Exposure to cold • Exercise • Infections- treated quickly with antibiotics • Immunisations

new gene therapies- CRISPR-Cas9

What type of cells may be observed after a splenectomy?

Howell-Jolly bodies

The presence of Howell–Jolly bodies usually signifies a damaged or absent spleen, because a healthy spleen would normally filter such erythrocytes

haemochromatosis

build up of iron in tissues