Sickle cell anaemia

Objective

At the end of this PDF Notes, student will be able to

•       Explain Sickle cell anaemia

•       Describe the pathogenesis of Sickle Cell Anaemia and Clinical features of it

•       Treatment of sickle cell anaemia

Sickle Cell Anaemia

•       Sickle-cell disease (SCD), or sickle-cell anaemia or  drepanocytosis, is an autosomal co-dominant
genetic  blood disorder characterized by red blood cell that  assume an abnormal, rigid, sickle shape.

Haemoglobinopathies: Haemoglobin in RBCs may be abnormally synthesised due to inherited defects. These disorders may be of two types:

•       Qualitative disorders e.g. sickle cell syndrome, other haemoglobinopathies.

•       Quantitative disorders e.g. thalassaemias.

Sickle syndromes occur in 3 different forms:

•       1. As heterozygous state for HbS: sickle cell trait (AS).

•       2. As homozygous state for HbS: sickle cell anaemia (SS).

•       3. As double heterozygous states e.g. sickle β-thalassaemia, sickle-C disease (SC), sickle-D disease (SD).

•       Sickle cell anaemia (SS) is a homozygous state of HbS in the red cells in which an abnormal gene is inherited from each parent.

•       Red blood cells typically live 90–120 days, but sickle  cells only survive 10–20 days

Pathogenesis of Sickle cell anaemia

1. Basic molecular lesion: single point mutation in one amino acid out — there is substitution of valine for glutamic acid –

–         6-residue position of the β-globin, producing Hb α2β2s2.

2. Mechanism of sickling: During deoxygenation, the red cells containing HbS change from biconcave disc shape to an elongated crescent-shaped or sickle-shaped cell- sickling

•       Form elongated rod-like polymers

•        Which align and distort the red cell into classic sickle shape

3. Reversible-irreversible sickling

4. Factors determining rate of sickling:

•        i) Presence of non-HbS haemoglobins

•       ii) Intracellular concentration of HbS.

•       iii) Total haemoglobin concentration.

•       iv) Extent of deoxygenation.

•       v) Acidosis and dehydration.

•       vi) Increased concentration of 2, 3-BPG in the red cells.

Sickle Cell Anemia vs. Sickle Cell Trait

•       People who have sickle cell anemia are born with it; means inherited, lifelong condition.

•       They inherit two copies of sickle cell gene, one from each parent.

•       Sickle cell trait is different from sickle cell anemia. People with sickle cell trait don’t have the condition, but they have one of the genes that cause the condition.

•       People with sickle cell anemia and sickle cell trait can pass the gene on when they have children.

Inheritance of Sickle Cell Anemia

•      If one parent has sickle cell anaemia (HbSS) and the other is completely unaffected (HbAA) then all the children will have sickle cell trait.

•       None will have sickle cell anemia.

•       The parent who has sickle cell anemia (HbSS) can only pass the sickle hemoglobin gene to each of their children.

•       If both parents have sickle cell trait (HbAS) there is a one in four (25%) chance that any given child could be born with sickle cell anemia.

•       There is also a one in four chance that any given child could be completely unaffected.

•       There is a one in two (50%) chance that any given child will get the sickle cell trait.

Clinical Features of Sickle Cell Anemia

•         Painful episodes

•         Pneumococcal disease

•         Acute chest syndrome

•         Splenic infarction

•         Splenic sequestration

•         Stroke

•         Osteonecrosis

•         Priapism

•         Retinopathy

•         Leg ulcers

•         Gallstones

•         Renal abnormalities

•         Osteopenia

•         Nutritional deficiencies

•         Placental insufficiency

•         Pulmonary hypertension

Complications of Sickle Cell Disease

Sickle Cell – Avascular Necrosis

Sickle Cell – Dactylitis

Sickle Cell Anemia – Treatment

•       Opiates and hydration for painful crises

•       Pneumococcal vaccination

•       Retinal surveillance

•       Transfusion for serious manifestations (eg stroke); exchange transfusion

•       Hydroxyurea

•       Stem cell transplant

Treatment of Sickle cell anaemia

—  Effective treatments are available to help relieve the symptoms and complications of sickle cell anemia, but in most cases there’s no cure.

—  The goal is to relieve the pain; prevent infections, eye damage, strokes and control complications if they occur.

—  Pain medicine: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and narcotics such as meperidine, morphine, oxycodone, and etc.

—  Heating pads

—  Hydroxyurea, Folic Acid

—  Blood Transfusions

Prevention of Sickle cell anaemia

—  Identify what can trigger the “Crisis” such as stress, avoid extremes of heat and cold weather, don’t travel airplane that is not cabin pressurized

—  Maintain healthy lifestyle habits

÷  Eating healthy

÷  Avoid dehydration

÷  Exercise regularly

÷  Get enough sleep and rest

÷  Avoid alcohol and don’t smoke

—  Regular medical checkups and treatment are important

Summary

•       Sickle-cell disease (SCD), or sickle-cell anaemia or drepanocytosis, is an autosomal co-dominant genetic blood disorder characterized by red blood cell that assume an abnormal, rigid, sickle shape.

•       Pathogenesis: Basic molecular lesion, Mechanism of sickling, Reversible-irreversible sickling,Factors determining rate of sickling

•       Sickle cell trait is different from sickle cell anemia. People with sickle cell trait don’t have the condition, but they have one of the genes that cause the condition